Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
330 Cards in this Set
- Front
- Back
|
What is the main substrate for muscle anaerobic glycolysis?
|
Intracellular glycogen.
|
|
|
What are the two advantages of breaking down glycogen as opposed to using blood glucose ?
|
Polymer means that breakdown of a glycogen molecules renders a lot of glucose and the glucose is already in the for of glucose-1-phosphate.
|
|
|
Why storing glycogen is important for a cell as opposed to fats (3 reasons) ?
|
1:Body need a carbohydrate storage2:Glycogen can be used faster than fats 3:Fats cannot be metabolized anaerobically.
|
|
|
How is glycogen used in the muscles?
|
Used as an energy source for fast supply.
|
|
|
How is glycogen used in the liver?
|
It is used to maintain glucose at a steady level in the blood. ( using gluconeogenesis)
|
|
|
Why can you still properly function for a short period of time when you stop breathing?
|
All tissues have their small glycogen storage for periods of hypoxia or anoxia in order to be able to do anaerobic glycolysis.
|
|
|
Which carbons are typically attached in the glycosyl residues in glycogen ? What is this bond called?
|
Carbon 1 to carbon 4. It is an alpha (1->4) bond
|
|
|
Which carbons are involved in the branching point bond of glycogen molecule? What is this bond called?
|
Carbon 1 to carbon 6. It is an alpha (1->6) bond.
|
|
|
What are the advantages of branching glycogen ends?
|
Allows multiple sites for synthesis and degradation.
|
|
|
What is a reducing end and How many of them a glycogen molecule usually have ?
|
It's a carbon 1 end that has a hydroxyl group attached to it (-OH) and a glycogen molecule usually has only 1.
|
|
|
What is the basic precursor reaction to synthesize glycogen?
|
Glucose-1-Phosphate ( from glucose-6-phosphate) + UTP --> UDP-glucoseUDP glucose is then used to synthesize glycogen.
|
|
|
What are the three processes involved in glycogen synthesis ?
|
creation of UDP-glucoseelongation of Glycogen moleculeBranching of glycogen molecule (alpha(1->6))
|
|
|
What is the kinetic outcome of the synthesis of UDP-glucose ( delta G)
|
Delta G= -33.5 kj/mol
|
|
|
How is UTP regenerated from UDP in the body? ( name the reaction including the enzyme)
|
UDP + ATP -- Nucleoside diphosphate kinase--> UTP+ ADP
|
|
|
What is the reaction for Glycogen elongation? What is the spontaneity of the reaction?
|
UDP-glucose + Glycogen(n) --> UDP + Glycogen (n+1)n: # of residues.This reaction is spontaneous.
|
|
|
What is the two names given to the enzyme responsible for creating new branching points on glycogen?
|
Amylo-(1,4->1,6)-transglycosylase or Branching enzyme
|
|
|
How many glycosyl residues are typically added to a newly made branch in a glycogen molecule ? What are the conditions (2) for a branching reaction to occur?
|
a ~ 7 glycosyl residue chain is transferred to a carbon-6 of a glycosyl residue of the same or different glycogen molecule. The conditions are:1: The segment must come from a chain of at least 11 residues.2: The segment must be branched at least 4 residues away from the other branch points.
|
|
|
What is the overall energy cost of the addition of one glucose to Glycogen?
|
2 ATP.
|
|
|
Describe the first reaction that breaks down glycogen. What does the enzyme require to do this work and what is this reaction's restriction?
|
Glycogen (n) + Pi --Glycogen phosphorylase--> Glycogen (n-1) + Glucose-1-phosphateGlycogen Phosphorylase requires a Phosphate to do its job. This reaction cannot occur closer than 5 residues from a branch point.
|
|
|
Which two enzyme are responsible for debranching a branch point and what do they respectively produce as a product?
|
1: alpha(1-4)glycosyl transferase which will cut a thrisaccaride section ( 3 residue) and attach it to a non-reducing end of a glycogen molecule.2: alpha(1-6) glucosidase: will produce a glucose molecule by detaching the last glycosyl residue in the branch.
|
|
|
What are the two products created by glycogen breakdown and in what proportions are they produced?
|
Glucose-6-phosphate ( 92%) and glucose (8%)
|
|
|
Why does alpha(1-4)glycosyl transferase can ony cleave (1-4) bonds in a glycogen molecule?
|
Because it requires a finite amount energy in order to do its work and only a (1-4) bond releases enough energy for this (16 units of energy)
|
|
|
How many units of energy a (1-4 bond) releases?
|
16 units
|
|
|
How many units of energy a (1-6 bond) releases?
|
8 units
|
|
|
Which enzyme transfers the phosphate from carbon 1 to carbon 6 on a glucose molecule ? What does it requires to do this ?
|
Phosphoglucomutase will do this, but it requires an attached phosphate as it does an exchange.
|
|
|
What is the fate of Glucose-6-phosphate post glycogen breakdown in:the liver?the muscles?
|
1: is converted back to Glucose 2: is sent down glycolysis
|
|
|
What is the efficiency of glycogen breakdown released energy of 1 residue compared to 1 molecule of glucose ?
|
the released residue will produce 39 ATP ( start at glucose-6-phosphate), but required 2 ATP to be stored in the first place so:39-2= 37 compared to 38 from a glucose molecule.
|
|
|
What is the overall reaction of the addition of one glyceryl residue to glycogen ?
|
Glucose+ 2 ATP + Glycogen (n) + H2O--> Glycogen (n+1) + 2 ADP + 2 Pi
|
|
|
What 2 regulatory mechanisms controls glycogen metabolism in the muscle?
|
1: Allosteric control ( by glucose and calcium )2: Covalent modification ( addition of phosphate)
|
|
|
What are the advantages (2) to having a cascade mechanism for glycogen metabolism in the muscle?
|
1: Respond to many effectors (flexibility)2: Amplification of the signal
|
|
|
How does a monocyclic enzyme cascade typically works?
|
The main enzyme will be regulated by two other enzymes: an up regulator and a down regulator. When the up regulator is activated by an external factor, it will phosphorylate the enzyme, typically activating it. When the activating factor for the up regulator is gone, the down regulator takes over and dephosphorylate the enzyme inactivating it.
|
|
|
What mode of regulation is typically dominant in a monocyclic enzyme cascade?
|
the main enzyme is controlled covalently.
|
|
|
What is the difference between a monocyclic and bicyclic enzyme cascade?
|
In a bicyclic enzyme cascade, one of the covalent regulators of the enzyme is also covalently regulated in a cycle.
|
|
|
What is the advantage of having a bicyclic enzyme cascade?
|
Potential of amplification and more regulation.
|
|
|
What are the two forms of an enzyme in a cyclic enzyme cascade mechanism and what type of mechanism regulates these forms?
|
There is the a (more active) form and the b (less active) form. These forms are governed by covalent modification ( in this case, phosphorylation)
|
|
|
What are the two confirmations of an enzyme in a cyclic enzyme cascade mechanism and what type of mechanism regulates these confirmations?
|
There is the T (inactive) confirmation and the R ( (active) confirmation. These are modulated by allosteric factors ( glucose and calcium in this case)
|
|
|
m-glycogen phosphorylase turns from the R state to the T state: what will happen to the enzyme?
|
Being in the T state it will be more susceptible to PP1c and will be turned into the b state, hence inactivating. ( prefix "m-" means modified enzyme which in this enzyme's case means in th a state)
|
|
|
What is Glycogen phosphorylase rate of activity determined by in the body ?
|
Its rate of modification/demodification
|
|
|
what are the 4 subunits of Phosphorylase kinase and what are their functions?
|
Alpha and Beta: get phosphorylatedGamma: catalytic subunitDelta: calmodulin ( calcium detector)
|
|
|
What regulates Glycogen phosphorylase?
|
Phosphorylase kinase
|
|
|
What does the prefix o- and m- means for an enzyme?
|
o- : unmodified m-: modifiedthis is in terms of covalent regulation in this pathway.
|
|
|
What happens to Phosphorylase kinase-b and a when [Ca2+] is high?
|
They both become active, a being much more than b.
|
|
|
What happens to Phosphorylase kinase-b and a when [Ca2+] is low?
|
b is inactive while a is in theory active but it will quickly be dephosphorylated by PP1c to become a b form.
|
|
|
What are the two types of inputs or type of factors that modulates Phosphorylase kinase?
|
Hormonal: causing cAMP increase.Neural : causing release of calcium.
|
|
|
What enzyme regulates phosphorylase kinase primarily and what compound regulates this regulatory enzyme?
|
Protein kinase A that is dependent on cAMP. Will phosphorylate Phosphorylase kinase.
|
|
|
What type of regulation modulates PKAs activity? How does this happen?
|
Allosteric regulation. cAMP binds to regulatory sites of PKA and will free the catalytic site for enzymatic activity.
|
|
|
Describe the mechanism modulating [cAMP] fluctuations in the cell. (4 steps) ( start with initial conditions)
|
1:no Hormone, G protein and GDP binds adenylate cyclase inactive.2:Hormone binds G protein GDP exchanged for GTP.3:G-protein GTP will bind adenylate cyclase and activates it.4: Hydrolysis of GTP inactivates the complex and return to initial conditions.
|
|
|
What modulates [cAMP] fluctuations in the cell?
|
hormone dependent G-protein activity with adenylate cyclase.
|
|
|
What is the difference between glycogen synthase and glycogen phosphorylase in terms of regulation?
|
Phosphorylation has opposite outcomes ( phosphorylation of glycogen synthase inactivates the enzyme)
|
|
|
What modulates glycogen synthase-b ? Is glycogen synthase-a affected by these?
|
It is sensitive to physiological concentrations of ATP, ADP and Pi when phosphorylated.glycogen synthase-a is not affected by these factors.
|
|
|
What can help glycogen synthase-b to activate?
|
Glucose-6-phosphate binding will favour glycogen synthase's dephosphorylation.
|
|
|
What glycogen synthase's activity dependent on ?
|
the fraction of dephosphorylated/phosphorylated states of the enzyme.
|
|
|
What is the catalytic subunit of PP1? In what conditions this subunit more active ?
|
PP1c which is more active when it is detached and free floating in the cell.
|
|
|
What is the subunit in the muscle that attenuates PP1c's activity in the cell when attached? Where is it situated?
|
Gm subunit which is attached to the glycogen molecule.
|
|
|
What are the two levels of regulation for PP1c in the muscle?
|
PP1c is regulated by being attached to the Gm subunit attached on glycogen, depending on Gm's phosphorylation state, PP1c will have a variation in affinity with the subunit. When insulin is in the body, Gm is less phosphorylated having a higher affinity for PP1c. When Gm is more phosphorylated, PP1c has less affinity and freed from regulation.
|
|
|
What is the main inhibiter of PP1c and how is this inhibiter regulated?
|
phosphoprotein phosphorylase inhibiter 1 inhibits PP1c. It is activated by PKA when phosphorylated.
|
|
|
How does PP1c get disinhibited by phosphoprotein phosphorylase inhibiter 1?
|
PP1c is in continuous activity, the inhibitor prevents it to access any substrate but itself. Eventually PP1c inactivates the inhibitor, free to dephophorylate the pathway.
|
|
|
What are the two hormones that can increase cAMP in the liver?
|
Glucagon and epinephrine
|
|
|
Which hormone affect the alpha and beta receptors in the liver and which metabolism factor each of these receptors affect?
|
Epinephrine will both affect the alpha receptor ( to increase calcium concentration with PIP2) and the beta receptor ( to increase cAMP concentration with adenylate cyclase)
|
|
|
What does glucose do to phosphorylase kinase in the liver?
|
If it is in the a form and R confirmation, glucose will shift the confirmation towards the T confirmation, which will quickly induce dephosphorylation and hence inactivation of the enzyme.
|
|
|
How is Phosphoprotein phosphotase 1 inactivated in the liver?
|
PP1 is attached to the glycogen binding subunit (Gl as opposed to Gm in muscle) and complexes with phophorilase kinase-a which inactivates the phosphotase.
|
|
|
Describe the interaction between PP1 and phosphorylase kinase a in the liver?
|
PP1 cannot dephosphorylate phosphorylase kinase a when in the R confirmation but it will immediately dephospharylate the enzyme when in the T state ( remember that they are complexed together)
|
|
|
Which state of phosphorilase kinase has the highest affinity to PP1?
|
phosphorilase kinase-a
|
|
|
What percentage of phosphorilase kinase has to be in the B from for PP1 to be active?
|
90% because of the high affinity of phosphorylase kinase-a has for PP1.
|
|
|
What enzyme is activated by phosphoprotein phosphotase 1?
|
Glycogen synthase
|
|
|
What is a synonym for vin Gierke's disease and this disease is defined by a deficiency of which enzyme?
|
Synonym: type 1 glycogen storage diseaseglucos-6-phophatase is deficient.
|
|
|
What is the function of glucose-6-phosphatase ?
|
Transform glucose-6-phosphate into glucose.
|
|
|
What happens with a patient with vin Gierke's disease?
|
Accumulation of glucose-6-phophate which inhibits phosphorylase kinase and activates glycogen synthase. Patient cannot maintain normal glucose levels in the body and have a higher glycogen content in tissues.
|
|
|
How can you treat Gierke's disease?
|
reduce glucose intake in the liver by bipassing the feeding vain such that glucose is given to the peripheral tissue before the liver ( less glycogen storage in the liver)
|
|
|
What is a synonym for McArdle's disease and this disease is defined by a deficiency of which enzyme?
|
Synonym: type V glycogen storage diseasemuscle phosphorylase kinase is deficient.
|
|
|
What happens with a patient with McArdle's disease?
|
Phosphorylase kinase will not activate glycogen kinase and hence the patient will be unable to respond to demand in energy.
|
|
|
Why does the symptoms of type V glycogen storage disease decrease after some time of exercise?
|
Because of the vasodilation which increase blood glucose supply to compensate for lack of energy.
|
|
|
What is a synonym for Her's disease and this disease is defined by a deficiency of which enzyme?
|
Type VI glycogen storage disease.Liver phosphorylase kinase is deficient.
|
|
|
What happens with a patient with Her's disease?
|
Lowered blood glucose concentration since phosphorylase kinase cannot respond to the demands of blood glucose in the liver.
|
|
|
What is the main metabolic mode of these two following tissues?Liver and muscle.
|
Liver does anabolic reactions, while muscle does catabolic reactions.
|
|
|
What are the three main metabolic pathways and their main products? Which of them is predominant in eukariotic cells ?
|
Anaerobic Homolactic fermentation: LactoseAnaerobic alcoholic fermentation: ethanol and carbondioxideAerobic oxidation: water and carbondioxide-> predominant in eukariotes.
|
|
|
Which Co-factor is crucial to be regenerated to maintain glycolysis ?
|
NAD+ must be regenerated in order to produce ATP and NADH.
|
|
|
Why PET imaging can be effectively used in the localization of a cancer by injection of radioactively labeled glucose in the body?
|
Cancer tissue have a high metabolic activity and prioritize anaerobic respiration to aerobic respiration. Although less efficient, anaerobic respiration allows for fast production of ATP. As a consequence, anaerobic respiration has a very high glucose consumption to maintain its high ATP production. Radioactively labeled glucose will accumulate the most in tissue that has high glucose consumption such as the cancer tissue. PET imaging allows for the localization of the labeled glucose, effectively finding the cancer.
|
|
|
How is glucose actively transported from the intestinal lumen in the capillaries and what other component of the cell maintains the function of this transport mechanism?
|
Glucose is co-transported with Na+ in the Glucose uniport. The Sodium/potassium pump pumps in Na+ and is hence crucial for the co-transportation of glucose.
|
|
|
How is glucose transported from the blood into the cell and why is it transported that way?
|
Through passive transport, glucose can effectively go down the concentration gradient into the cell because the concentration of blood glucose is 5mM and cells constantly use glucose effectively lowering its concentration.
|
|
|
What does the SGLUT 1 do and where is it ?
|
SGLUT 1 co-transports glucose with 2 Na+ molecules and is located in the intestinal mucosa and kidney tubules.
|
|
|
What does the GLUT 2 do and where is it ?
|
GLUT 2 transport fructose, glucose and galactose and has low affinity for all these sugars. It is a glucose sensor for pancreatic beta cells and is located in the liver pancreas, small intestine and kidney.
|
|
|
What does the GLUT 4 do and where is it ?
|
The insulin- responsive glucose transporter. It has a high affinity for glucose. It is in skeletal and cardiac muscles.
|
|
|
Why does the body comprise of such a variety of glucose transporters ?
|
The variety allows the transport to be tailored to the needs of each tissue. The variety comes in amounts of expression and ratios. It also allows a tissue to be specialized in a specific sugar.
|
|
|
Why is glucose phosphorylated once in the cell ( 2 reasons) and which enzyme does this at the expenditure of what?
|
Phosphorylation will: 1: trap glucose in the cell ( G6P) 2: Keep glucose's concentration down in order to maintain the concentration gradient such that glucose continues to be taken up.Glucose is phosphorylated by hexokinase at the expenditure of 1 ATP.
|
|
|
What are the enzymes of the three irreversible steps of glycolysis and why are they important?
|
the three enzymes are hexokinase, phosphofructokinase and Pyruvate kinase. They are important as they not only regulate glycolysis in order to respond to the supply and demands of the cell, but they also give directionality to glycolysis, committing the reactants to the pathway. (The production of 4 ATP to reimburse the spending of 2 ATP is only at the end of the pathway hence you need to get through it.)
|
|
|
What is the overall reaction set catalyzed by Hexokinase?
|
Glucose + ATP --Mg2+--> Glucose-6-phosphate + ADP
|
|
|
What are the three types of Hexokinases, where are they and how are they regulated?
|
Hexokinase 1: most tissue: glucose-6-phosphateHexokinase 2: muscle, adipose tissue:glucose-6-phosphateGlucokynase: liver, pancreas: GKRP (Glucokinase regulatory protein)
|
|
|
What does Glucokinase do and how is it regulated?
|
Glucokinase is kept in the nucleus by the glucokinase regulatory protein and is released in the soma when glucose concentration is high, converting it to glycogen
|
|
|
What is the overall reaction set catalyzed by Phosphofructokinase and its regulators?
|
fructose-6-phosphate + ATP --Mg2+--> fructose-1,6-bisphosphate + ADPActivators: ADP, AMP and Fructose-2,6-bisphosphateInhibitor: ATP
|
|
|
Why glycolytic flux can increase by 100%, while only having a 10% drop in ATP during vigorous exercise?
|
AMP will relieve ATP inhibition of phosphofructokinase allowing effective continuation of glycolysis. ATP drop is stalled by adenylate cyclase using to ADP to produce AMP and ATP. This creates a significant increase in AMP levels while maintaining relatively stable levels of ATP. For a 10% ATP drop you have a 4x increase in AMP disinhibiting PFK.
|
|
|
Assuming [ATP]>>[AMP] and the total concentration of Adenine is constant in the cell ([ATP]+[ADP]+[AMP]=At), derive an equation of AMP in terms of ATP and At using the following:K=[ATP][AMP]/[ADP]^2=0.44
|
1: isolate [AMP] from the k equation2: Assuming there is very little AMP At=[ATP]+[ADP], hence isolate [ADP] and substitute this equation for [ADP] in equation 1Result: [AMP]=0.44x[At-[ATP]]^2/[ATP]
|
|
|
Assuming that [ATP]/[ADP] of 10 and At([ATP]+[ADP]+[AMP])=5mM, calculate the ratio of final vs initial concentrations of [AMP] on a 10% decrease of ATP.
|
1: there is very little [AMP] hence you can use the values [ATP]=4.5mM and [ADP]= 0.45mM to calculate initial [AMP] using [AMP]=0.44x[At-[ATP]]^2/[ATP]2: do the same using the values [ATP]=4.05mM and [ADP]= 0.405mM
|
|
|
What phenomenon allows the rate of glycolysis to increase by 100X when increase in 4x AMP will only increase PFK by 9X?
|
Substrate cycle of Fructose-6-phosphate.
|
|
|
What is the Cycle of Fructose-6-phosphate and what are the key regulators? What is the issue if this cycle is not regulated?
|
F6P+ATP--PFK-->F1,6P + ADPF1,6P + H2O --FBPase--> F6P+PiAMP and F2,6P->activates PFK and inhibits FBPase.issue: results in the net hydrolysis of ATP
|
|
|
What does the Fructose-6-phosphate cycle enables the muscle to do ?
|
It enables muscles to have a low glycolysis rate at rest, but respond quickly to a demand of energy.
|
|
|
How many times is phosphofructokinase more active than FBPase?
|
Phosphofructokinase 10 x more active than FBPase.
|
|
|
What is the difference in activity between phosphofructokinase and FBPase when [AMP] is low and when it increase by 4 folds?
|
PFK is 10x more active than FBPase. 4x more AMP = 9x more activity in PFK and the opposite effect happens to FBPase. Assume PFK activity=100 and FBPase=10. and AMP flux will modify activity of PFK and FBPase from 10% and 90% to 90% and 10%.Low AMP: 10%x100 - 90%x10=10-9=1 (low activity)High AMP: 90%x100 - 10%x10=90-1=89 (high activity)
|
|
|
What is the role of Fructose-2,6-bisphosphate in glycolysis?
|
It is a potent activator of phosphofructokinase and inhibitor of fructose bisphosphatase.
|
|
|
What modulates the concentration of fructose 2,6 bisphosphate ? how are these factors related?
|
phosphofrutokinase-2's synthesis and fructose bisphosphate-2's degredation. They are part of the same protein.
|
|
|
What would happen inside the liver if there is a drop of glucose concentration in the blood?
|
decrease in glucose will trigger an increase in glucagon which will signal the liver to increase its concentration of cAMP. This will result in a reduction of fructose-2,6-bisphosphate and decrease phosphofructokinase activity ( by extension glycolysis) favouring gluconeogenesis.
|
|
|
What can stress do to the liver?
|
Trigger glucagon secretion which in turn will activate the liver to do gluconeogenesis.
|
|
|
What regulates the PFK-2/FBPase-2 isozymes in the liver? Why does this regulator have a different effect on the heart?
|
PKA. PKA affects different sites of different PFK-2/FBPase-2 isozymes in the heart.
|
|
|
What would be the effect of a net increase in Stress have on the heart?
|
Increase stress will increase the secretion of epinephrine which in turn will increase the concentration of cAMP, increasing the concentration of fructose-2,6-bisphosphate activating PFK activity.
|
|
|
What is different in the Muscle PFK-2/FBPase-2 isozymes?
|
it is not regulated by cAMP, but by a the AMP-dependent protein kinase (AMPK)
|
|
|
What would be the effect of a net increase in stress on the muscle?
|
Increase stress will increase the secretion of epinephrinewhich in turn will increase the concentration of AMP, increasing theconcentration of fructose-2,6-bisphosphate activating PFK activity.
|
|
|
What does Aldolase do in glycolysis? How many types?
|
It seperates fructose-1,6-bisphophate to glycealdehyde-3-phosphate ( GAP) and dihydroxyacetone phosphate (DHAP)2 types
|
|
|
What does Triose phosphate isomerase do in glycolysis? Being bidirectional, why does this enzyme favour one side of the reaction?
|
it catalyses the Interconversion of glycealdehyde-3-phosphate ( GAP) and dihydroxyacetone phosphate (DHAP). [GAP] is kept low due to usage of the glycolytic pathway, favouring its production.
|
|
|
What does glycealdehyde-3-phosphate dehydrogenase do in glycolysis?
|
catalyses the generation of 1,3-bisphosphoglycerate and NADH.
|
|
|
What does Phosphoglycerate kinase do in glycolysis?
|
converts 1,3-bisphosphoglycerate to phosphoenolpyruvate and creates ATP ( a for each 3 carbon molecule)
|
|
|
The reaction of Phosphoglycerate kinase has a delta G=-18.8Kj which suggests that the reaction is irreversible but it is not in the body. Why the discrepancy?
|
The Keq is very high (2060), meaning that 1,3-bisphosphoglycerate does not accumulate to a significant amount passing rapidly to the next reaction creating a delta G of 0.1Kj (reversible reaction).
|
|
|
What does Pyruvate Kinase do in glycolysis? What are his regulators?
|
it converts phosphoenolpyruvate to pyruvate and generates ATP.Inhibitor: ATP, glucagon, cAMP, PKA.Activator: Fructose-1,6-bisphosphate
|
|
|
What is the final energetic outcome of glycolysis?
|
Uses 2 ATP to produce 4 ATP and 2 NADH
|
|
|
What happens to NADH when it takes the malate-aspartate shuttle and where is this shuttle located?
|
NADH will be converted and regenerated to become matrix NADH in the mitochondria. Here it will go through complex 1 and through the whole electron chain to produce 3 ATP. This shuttle is in most tissues.
|
|
|
What happens to NADH when it takes the glycerophosphate shuttle and where is this shuttle located?
|
NADH will be converted and generated into FADH2 which will only enter complex 2 of the electron chain in the mitochondria.Hence, it will only produce 2 ATP. This shuttle is in fast work tissues.
|
|
|
What happens to NADH when glycolysis is faster than oxidative phosphorilation?
|
NADH will be used to convert pyruvate into lactate. (anaerobic homolactic fermentation)
|
|
|
What is the pros and cons of using the glycerophosphate shuttle?
|
This shuttle can be used despite having very low concentrations of NADH. It however produces less ATP.
|
|
|
What is the difference between slow-twitch and fast-twitch skeletal muscle?
|
Slow-twitch has high mitochondria content and is considered red tissue ( endurance work)Fast-twitch has low mitochondria content and is considered white tissue (short burst work)
|
|
|
What is the final energetic value of:1:Aerobic glycolysis2:Anaerobic glycolysis3:mitochondrial oxidative phosphorylation
|
1: 8 ATP (NADH used in ox.pho.)2: 2 ATP3: 38 ATP ( includes aerobic glycolysis)
|
|
|
What is SMR in metabolic biochemistry?
|
Standard metabolic rate: rate of metabolic reaction without food intake and under resting stress free conditions
|
|
|
What is a:1: negative energy balance2: positive energy balance
|
1: Energy spent> energy taken2: Energy spent< energy taken
|
|
|
What is Metabolism composed of ( 2 types of reactions) and what do these components do ?
|
Metabolism= Anabolism + CatabolismAnabolism =biosynthesisCatabolism=degradation
|
|
|
What are the 5 principles of Metabolic pathways and their implication?
|
1: They are irreversible ( which gives directionality)2: Catabolic and Anabolic reactions differ ( to make them interconvertible and controllable)3: Needs a first committing step ( directionality)4: Must be regulated ( follow law of supply and demand)5:Must occur in specific locations ( different conditions and restrain the toxic bi-products)
|
|
|
Where does the following occur?1:Glycolysis2:Citric Acid cycle3:Oxidative phosphorylation4:Fatty acid oxidation5:Fatty acid biosynthesis6:Pentose Phosphate Pathway
|
1: Cytosol2: Mitochondrion3: Mitochondrion4: Mitochondrion, Peroxisomes5: Cytosol6: Cytosol
|
|
|
What is the Gibbs free energy equation ( from a given reaction A+B->C+D and why is it useful?
|
delta G= dalta G°+ RT ln ([C][D]/[A][B]). It gives a good indication of the spontaneity of a reaction.
|
|
|
Living organisms are open systems and can never be at equilibrium. What are the 3 reasons for this and consequently in what state are all living conditions ?
|
1: only non-equilibrium processes can do work2: a process at equilibrium cannot be directed3: living organisms must have a constant energy intake to be active.Living organisms are in a steady state where the flow of the system is constant and perturbation will always be countered by the system.
|
|
|
In what conditions enzymatic reactions in metabolism usually function to and how are the regulating reactions differ from this?
|
enzymatic reactions in our metabolism function close to equilibrium and regulating reaction functions far from equilibrium.
|
|
|
For the past 70 years, to what is the increase of type 2 diabetes in the United-States correlated to?
|
An increase in consumption of carbohydrates coming from high fructose corn syrup.
|
|
|
What are the three main usages of carbohydrates in the body?
|
Carbohydrates are:1: used for energy consumption (glycolysis incorporation)2: Converted to glycogen3: Converted to fats
|
|
|
In the body what is starch converted into ?
|
Glucose
|
|
|
In the body what is Lactose converted into ?
|
Galactose + glucose
|
|
|
In the body what is sucrose converted into ?
|
Glucose + Fructose
|
|
|
Where does most of the metabolism of carbohydrate occur ?
|
In the liver
|
|
|
How is Fructose metabolized in the muscles? (name the enzyme(s) involved and the fate of the final product)
|
Fructose is taken directly by Hexokinase and is converted to Fructose-6-phosphate and is directly sent to glycolysis.
|
|
|
What is the name of the enzyme which phosphorylates fructose when entered in the liver
|
Fructokinase
|
|
|
Describe the first enzymatic reaction that occurs to fructose when metabolized by the liver.
|
Fructose +ATP --Fructokinase-->Fructose-1-phosphate + ADP
|
|
|
Describe the second enzymatic reaction that occurs to fructose when metabolized by the liver. In what confirmation must the reactant be in order for this reaction to work?
|
Fructose-1-phosphate --fructose-1-phosphate aldolase--> glyceraldehydeFructose-1-phosphate must be in an open chain confirmation.
|
|
|
Describe the final enzymatic reaction that occurs to fructose when metabolized by the liver. What is the fate of the final product?
|
glyceraldehyde --glyceraldehyde kinase--> glyceraldehyde-3-phosphateglyceraldehyde-3-phosphate will be sent in glycolysis.
|
|
|
What is the difference between the products of the muscle metabolism versus the liver metabolism of fructose. Why is this a concern?
|
In the muscle, fructose will be processed as Fructose-6-phosphate which enter glycolysis before its major point of control: PFK. In the liver, Fructose is metabolised in glyceraldehyde-3-phosphate which enters past the main control point. This is believed to be related to the excess carbohydrate consumption seen in our society today.
|
|
|
What is the cause of Fructose intolerance?
|
It's a genetic disorder where Fructose-1 phosphate aldolase is missing.
|
|
|
What is the issue of not having Fructose-1-phosphate aldolase in the liver?
|
Fructose metabolism will be interrupted at its first step, increasing the amount of Fructose-1-phosphate, lowering Pi concentration in the blood, which in turn lowers ATP production.
|
|
|
Describe the first enzymatic reaction that occurs to galactose when metabolized by the liver.
|
Galactose + ATP --galactokinase--> galactose-1-phosphate+ADP
|
|
|
Describe the second enzymatic reaction that occurs to galactose when metabolized by the liver and the cycle that reacts with it.
|
galactose-1-phosphate+UDP-glucose --galactose-1-phosphate udylyl transferase--> UDP-galactose + Glucose-1-phosphatecyclic side reaction: UDP-glucose --galactose-1-phosphate udylyl transferase--> UDP-galactose ( part of metabolic pathway)UDP-galactose --UDP-galactose-4-epimerase + NAD+--> UDP-glucose(regenerate UDP-glucose)
|
|
|
What happens to Glucose-1-phosphate when it is influenced by phosphoglucomutase?
|
It reversibly becomes Glucose-6-phosphate and can go in glycolysis.
|
|
|
What are the three types of galactosemia and which enzyme is affected in each type?
|
Type I: no uridylyl transferaseType II: no galactokinaseType III: no epimerase
|
|
|
Which type of galactosemia is the most common and which is the most severe ?
|
Type I is the answer to both questions. Not only the most common, that galactose is converted to glactose-1-phosphate which lowers blood Pi concentration and by extension ATP concentration.
|
|
|
Would removing galactose from one's diet be sufficient to treat a galactosemia?
|
No, since lactose is metabolised in galactose and glucose. Need to remove lactose as well.
|
|
|
How is lactose made in the body? ( describe the reaction)
|
UDP-galactose + glucose--lactose synthase--> lactose
|
|
|
How can a galactosemic mother produce breast milk for her child?
|
The reaction of UDP-galactose-4-epimerase can be reverted with the coupling of an other reaction which is the following:UTP + Glucose-1-phosphate--> UDP glucosewhich is highly exergonic and hence allows the inverse of the epimerase reaction. coupled with glucose, UDP-galactose can form lactose.
|
|
|
What are the three usages of the Pentose Phosphate Pathway ?
|
1:Produce NADPH2:Produce Pentose Sugars 3:Utilize Pentose Sugars
|
|
|
All the steps of the Pentose phosphate pathway can be divided in what two general types ?
|
1:Oxidative steps2:Non-oxidative steps
|
|
|
Cells have both NAD and NADP, why?
|
NADH is used for catabolic reactionsNADPH is used for anabolic reactions These two co Factors are not interchangeable as metabolic enzymes are highly specific for either one of them.
|
|
|
What is the difference in productivity of one molecule of NADH vs NADPH in terms of number of metabolites affected ?
|
1 NADH: 1000 metabolite oxidations1 NADPH: 0.01 metabolite reduction
|
|
|
Why is the pentose phosphate pathway virtually absent in muscles?
|
Muscles do not require Anabolic reactions
|
|
|
Where does the pentose phosphate pathway branch out in glycolysis ( which substrate is affected)?
|
At the Glucose-6-Phosphate step.
|
|
|
Where does the pentose phosphate pathway mostly occur ? ( 3 places)
|
1 liver2 Adipose cells3 Red blood cells
|
|
|
What are the three stages of the pentose phosphate pathway and which one of them are reversible ? Why?
|
1 Oxidative reactions (steps 1-3)2 Isomerization and epimerization reactions (steps 4-5)3: C-C bond cleavage and formation reactionsStages 2 and 3 are reversible to better respond to the needs of the cell.
|
|
|
What are the products of the oxidative stage of the pentose phosphate pathway?
|
NADPH and Ribulose-5-Phosphate
|
|
|
Which step is regulatory for the pentose phosphate pathway in the oxidative stage? What is its main inhibiter?
|
The first reaction, as it is irreversible and highly regulated. Specific for NADP+ and strongly inhibited by NADPH.
|
|
|
What is the overall reaction of the oxidative stage of the pentose phosphate pathway?
|
3 glucose-6-phosphate + 6 NADP+ + 3 H2O-->6 NADPH + 6 H+ + 3 CO2 + 3 Ribulose-5-Phosphate
|
|
|
What is the overall reaction of the isomerization and epimerization reactions stage of the pentose phosphate pathway?
|
3 Ribulose-5-Phosphate <---> Ribose-5-phosphate + Xylulose-5-phosphate
|
|
|
What is the enzyme involved with :1: isomerization 2: epimerizationin the isomerization and epimerization reaction stage of the pentose phosphate pathway?
|
1: Ribulose-5-Phosphate isomerase2: Ribulose-5-Phosphate epimerase
|
|
|
What does an isomerization reaction do?
|
Will interchange groups between carbons
|
|
|
What does an epimerase reaction do?
|
Will interchange groups between the same carbon.
|
|
|
What product of the Pentose phosphate pathway is a precursor to nucleotide synthesis and what is it converted into if in excess?
|
Ribose-5-Phosphate. If too much is accumulated, it will be converted in GAP and fructose-6-phosphate.
|
|
|
What is the overall reaction of the C-C bond cleavage and formation stage of the pentose phosphate pathway?
|
Ribose-5-phosphate + 2 Xylulose-5-phosphate <--> 2 fructose-6-phosphate + glyceraldehyde-3-phosphate
|
|
|
What are the two enzymes involved in the C-C bond cleavage and formation stage of the pentose phosphate pathway?
|
Transketolase (step 6 and 8 of pathway)Transaldolase (step 7 of pathway)
|
|
|
The activity of the pentose phosphate pathway is determined by the relative activity of which two enzymes? What is their common substrate?
|
Glucose-6-phosphate is the substrate for glucose-6-phosphate dehydrogenase and phosphofructo kinase. Their relative activity will determine the rate of the pentose phosphate pathway.
|
|
|
What modulates the activity of glycolysis vs the Pentose phosphate pathway ( 2 enzymes and their inhibiters)?
|
Concentration of ATP for phosphofructo kinase activity ( high=inhibtion) and concentration of NADPH for glucose-6-phosphate dehydrogenase (high=inhibition)
|
|
|
What three factors are taken into account for the activity of the Pentose Phosphate Pathway?
|
Demands of ATP, NADPH and ribose-5-phosphate
|
|
|
What happens to the pathway when both NADPH and Pentose sugars are needed?
|
The first two stages are dominant and produces NADPH (stage 1) and Pentose sugars (stage 2)
|
|
|
What happens to the pathway when more NADPH than Pentose phosphate are needed?
|
Transaldolase and transketolase will convert excess pentose sugars into fructose-6-phosphate and glyceraldehyde-3-phosphate.
|
|
|
What happens to the pathway when more Pentose sugars than NADPH are needed?
|
Fructose-6-phosphate and glyceraldehyde-3-phosphate can be converted back to pentose sugars by transaldolase and transketolase.
|
|
|
What is the importance of NADPH for red blood cells?
|
they produce hydrogen peroxide that would destroy their membrane and the membrane of any cell. Glutathione peroxidase will eliminate these peroxides using glutathione. NADPH will regenerate glutathione after the reaction.
|
|
|
What is the overall reaction of glutathione peroxidase?
|
2 Glutathione + R-OOH -glutathione peroxidase-> glutathione disulfide + R-OH +H2O
|
|
|
What is the overall reaction of glutathione reductase?
|
glutathione disulfide + NADPH -glutathione reductase-> 2 Glutathione + NADP
|
|
|
What is the most common human enzymopathy?
|
Glucose-6-phosphate dehydrogenase deficiency
|
|
|
Why virtually only males suffers from Glucose-6-phosphate dehydrogenase deficiency?
|
Because it is a x-linked trait.
|
|
|
What is the most probable cause of Glucose-6-phosphate dehydrogenase deficiency?
|
The breakdown of the mutant enzyme ( too quick)
|
|
|
What does a Glucose-6-phosphate dehydrogenase deficiency cause?
|
Hemolyptic anemia ( break down of red blood cells) because glutathione cannot be regenerate which eventually results in the breakdown of red blood cells by R-OOHs.
|
|
|
Why is Glucose-6-phosphate dehydrogenase deficiency self limiting?
|
because there is an equilibrium where new blood cells with more enzymes to cope with the R-OOHs replace the old ones that get degraded.
|
|
|
Describe the first reaction of the pentose phosphate pathway.
|
Glucose 6 phaphate + 3 NADP+ - glucose-6-phosphate dehydrogenase-> 3 NADPH + 6-phosphoglucono-delta-lactone.
|
|
|
Describe the third reaction of the pentose phosphate pathway.
|
6-phospho-gluconate + 3 NADP+ -6-phospho-gluconate dehydrogenase-> ribulose-5-phosphate + 3 NADPH + CO2
|
|
|
What substrates are required in order to obtain 2 furtose-6-phosphate and glyceraldehyde-3 phosphate from the C-C Bond cleavage and formation reaction stage ? How many times did the upper stages (stage 1 and 2) passed to obtain this results?
|
you need: 1 ribose-5-phosphate and 2 xylulose-5-phosphate. Stage 1 and 2 occurred three times to have all these substrates.
|
|
|
Describe the reactions that occurs in the C-C Bond cleavage and formation reaction stage.
|
1: Ribose-5-phosphate (5 C) + xylulose-5-phosphate (5 C) are taken up by transketolase to form GAP (3 C) and Sedoheptulose-7-P (7 C). 2: These are further transformed by transaldolase to form Fructose-6P (6 C) and Erythrose-4P (4 C). 3: Erythrose-4P reacts with another xylulose-5P with the aid of transketolase to form fructose-6P and GAP again. Overall result is 2 x Fructose-6P and GAP.
|
|
|
Why are enzymes powerful catalysts ? ( 2 reasons)
|
1: They have a very high specificity for its substrate binding 2: They induce optimal arrangement of catalytic groups in the active sites
|
|
|
What two characteristic thing does an enzyme do in a reaction?
|
1: Enzymes are unchanged at the end of the reaction2: Enzymes do not affect the equilibrium constant.
|
|
|
Are enzyme's effects unidirectional?
|
No they affect both the forward and reverse reaction.
|
|
|
What is the difference between enzymes and chemical catalysts ? (2)
|
1: Enzymes are proteins ( much larger than the substrate).2: Display structural and stereo specificity.
|
|
|
From where does the specificity of the enzymes comes from ?
|
The structure of the active site.
|
|
|
What is a characteristic of the active site in terms of amino acids?
|
They are from different parts of the sequence and only a few will actually bind the substrate.
|
|
|
What is the (general) function of the amino acids that are not part of the active site for an enzyme ?
|
serve as a scafforld for the 3D structure of the active site
|
|
|
What can the amino acids that are not part of the active site be involved with (4 things)?
|
1: Regulatory sites 2: Interaction with other proteins3: Channels to bring substrate to active site4: Cellular localization
|
|
|
What complex is indicative of the enzymatic activity on a reaction?
|
The enzyme-substrate complex
|
|
|
What are the two factors that creates the specificty of the formation of the enzyme-substrate complex?
|
1: Required complimental charges to bind 2: Structure of the active site that is specific
|
|
|
What are the four interactions that are usually involved in a substrate binding on an enzyme?
|
1: Hydrogen bond2: Van der waals interactions3: electrostatic interactions4: Hydrophobic interactions
|
|
|
What is the Van der waals interaction?
|
Interaction between two compounds through their dipole moments created according to the electrostatic properties and arrangement of the elements composing the compound.
|
|
|
What are the 6 possible catalytic mechanisms?
|
1: Acid-Base catalysis2: Covalent catalysis3: Metal ion catalysis4: Electrostatic catalysis5: catalysis through proximity and orientation effects6: Preferential binding of transition state
|
|
|
What is a simplistic way to explain the pK of a molecule?
|
The pK is the pH at which the molecule has a 50% protonated and 50% deprotonated states.
|
|
|
What is the characteristic of a acid-base catalysis enzyme?
|
One of the amino acids of the side chain in the active site will act as an acid or a base to render "base like" or "acid like" conditions to a reaction in a cell with a neutral pH.
|
|
|
How is the acceleration of the reaction achieved in an acid-base catalysis ?
|
It is achieved through a catalytic transfer of a proton.
|
|
|
If a compound has a pK of 3, what form this compound will most likely be at a neutral pH ?
|
It will most likely be deprotonated (wanting to acidify the pH)
|
|
|
What is a synonym for covalent catalysis ? What is the menaing of that synonym?
|
Nucleophilic catalysis ( "nucleus lover" which means that the compound is electron rich).
|
|
|
What are the two condition for an effective covalent catalytic enzymes?
|
1: nucleophilic ( acts like it)2: forms a good leaving group
|
|
|
What transient bond is formed in a covalent catalysis?
|
a trasient covalent bond.
|
|
|
How are nucleophiles usually activated?
|
through the deprotonation by a general base.
|
|
|
What is the target of a nucleophile ( type of molecule) /
|
An electrophile since they are proton defficient.
|
|
|
What are two examples of enzymes that usually involve covalent catalysis?
|
Pyruvate dehydrogenase complex reactions and proteolytic enzymes.
|
|
|
What proportion of enzymes require a metal ion for proper functionning ?
|
1/3 of the enzymes
|
|
|
What is the difference between a metaloenzyme and a metal activated enzyme? what are a few examples of typical metal ions for each type?
|
Metaloenzyme has a tightly bound metal ion to it while the metal activated enzyme is loosely bound. eg metaloenzyme ion: Fe (2 or 3+) Zn2+, Cu2+, Mn2+,Ca2+eg metal activated enzyme ions: Na+, K+, Mg+, Ca+
|
|
|
What is the primary relevance of metal ion enzymes in metabolic chemistry?
|
It is heavily involved in the electron transport chain.
|
|
|
Why is water usually excluded from the active site of a electrostatic catalytic enzyme during a reaction?
|
This lowers the dielectric constant resulting in more reactive substrates as their charde is not "diluted" by the dipole moments of water.
|
|
|
What is the dielectric constant of a solvant? What does a low dielectric constant favors?
|
Ability of a solvent to keep opposit charges appart. A low dielectric constant favours electrostatic interactions.
|
|
|
How does a catalysis through proximity and orientation effects work?
|
By binding the substrates on a single binding surface, hence orienting then for the reaction and optimizing its rate.
|
|
|
What is an equivalant analogy of having reactants being in proximity and correct orientation to one another?
|
It is similar to increasing the concentration of each reactant.
|
|
|
What could explain why an enzyme would preferentially bind the transition state of a substrate?
|
The increase of covalent bonds between the active site and the substrate when the substrate reaches the transition state.
|
|
|
What is the most probable mechanism behind a preferential binding of the transition state complex?
|
Substrate binding to the enzyme's active site can cause a confirmationnal change in the active site which in turn deforms the substrate putting it in a transition like state. The released energy induced by this change can be used for the reaction to occur. The strained substrate fits better the enzyme than the normal substrate.
|
|
|
What are potential inhibitors of an enzyme that preferentially binds the transition state of a substrate?
|
Analogues of the enzyme's substrate's transition state structure. They will tightly bind the enzyme, but they will not be catalysed.
|
|
|
What is the presumed origin of the mitocondria?
|
Through a symbiotic relationship between eukariotic cell that relied on glycolysis as energy and an oxidative bacterium.
|
|
|
What modulates the efficency of the mitochondrias in a cell?
|
their flexible variation in their shape and also of fusion/seperation.
|
|
|
What are the main functions of the mitocondria? (5)
|
Mediates the citric acid cycle, the pyruvate dehydrogenase complex, fatty acid oxidation, electron transport and oxidative phosphorilation.
|
|
|
Why are there numerous folds in the inner mitochondrial membrane?
|
A lot of the enzymes are membrane bound in the IMM. increasing the surface of the IMM with fold will increase the number of membrane bound enzymes such as the electron chain complex.
|
|
|
Why does the outer mitochondrial membrane let any molecule of 10kDa and less diffuse freely? Name the molecule involved.
|
It contains porins, a protein that forms a large aqueous channel through the lipid bilayer
|
|
|
How do compounds get into the inner membrane space ?
|
Specific transport mechanisms on the inner mitochondrial membrane.
|
|
|
What is the percentage of protein content by weight of the Inner mitochondrial membrane?
|
80%
|
|
|
What does the high content of cardiolipin give as an attribute to the inner mitochondrial membrane?
|
Very impermeable to ions.
|
|
|
What is the name of the inner folds of the inner mitochondrial membrane ?
|
Cristae
|
|
|
How can you determine the protonated form of a compound in given conditions?
|
By comparing the pK of each acidic/basic groups with the pH of the medium.
|
|
|
What characteristic structures of the mitochondria suggests its bacterial ancestry? (2)
|
1: It has an inner and outer membrane 2: It has a circular DNA
|
|
|
How many polypeptides are coded in the mitochondrial genome and what is how many are devoted to the electron transport chain
|
13 polypeptides comes from the mitochondria and 11 are for the electron transport chain.
|
|
|
Why most of the mitochondrial proteins are coded in the nucleus and synthesized in the cytoplasm and transported in the mitochondria?
|
The mitochondria is the main producer of oxygen reactive species which highly damages DNA. Minimizing DNA content in the mitochondria will minimize alteration risks.
|
|
|
How many types of Tim are in the mitochondria and what are their purpose?
|
2 types: one to produce free floating proteins while the other is for inter membrane proteins?
|
|
|
What compound inhibits mitochondrial protein synthesis and what is its mechanism?
|
Chloramphenicol. It inhibits peptidyl transferase reactions in protein synthesis.
|
|
|
What is the general given name for the mitochondrial outer membrane channel that allows protein transport in the mitochondria.
|
It is usually referred as Tom. (Tom 40,70,20,22)
|
|
|
What are three example of sources of acetyl coA?
|
1: Pyruvate2: Fatty acid3: amino acid
|
|
|
What is the primary function of the pyruvate dehydrogenase complex ?
|
It catalyses the decarboxylation of pyruvate into acetyl coA.
|
|
|
Where does pyruvate have to go to get affected by the pyruvate dehydrogenase complex and what transporter brings it there? What type of transporter is it ?
|
It has to go to the mitochondria. the pyruvate translocase will bring it inside the mitochondria. It is a H+ symport.
|
|
|
How does a symport work?
|
It couples the transport of a molecule down its concentration gradient (exergonic) with a molecule up its concentration gradient (endergonic). This allows the unfavorable transport to happen.
|
|
|
How is ADP and ATP transported in and out of the mitochondria?
|
With the ADP/ATP antiport
|
|
|
What is the proton gradient in the mitochondria ( inter membrane space vs inner space) and by what is it maintained?
|
[H+] inter membrane space >> [H+] inner space.This is maintained by the electron transport chain.
|
|
|
What is the name of the most important proton transporter in the mitochondria?
|
ATP synthase.
|
|
|
What is the name of the E1 subunit of the Pyruvate dehydrogenase complex?
|
Pyruvate dehydrogenase.
|
|
|
What is the name of the E2 subunit of the Pyruvate dehydrogenase complex?
|
Dihydrolipoyl transacetylase
|
|
|
What is the name of the E3 subunit of the Pyruvate dehydrogenase complex?
|
Dihydrolipoyl dehydrogenase.
|
|
|
What are the two additional enzymes that control the Pyruvate dehydrogenase complex's activity?
|
There is pyruvate dehydrogenase kinase and pyruvate dehydrogenase phosphotase.
|
|
|
What are the four vitamins essential for the Pyruvate dehydrogenase complex?
|
1: Thiamine2: Panthotenic Acid3: Riboflavin4: Niacin
|
|
|
What vitamin give rise to the cofactor coenzyme A?
|
Panthotenic Acid.
|
|
|
What can a deficiency in thiamine cause ?
|
Beriberi syndrom ( loss of neural function).
|
|
|
What system in the body is especially dependent on the Pyruvate dehydrogenase complex and for what reason?
|
The central nervous system as brain tissue do not have reserves of glycogen ( poor at anaerobic respiration).
|
|
|
What two organs consumes the biggest amount of glucose?
|
The heart and the brain.
|
|
|
What is the overall reaction mediated by the pyruvate dehydrogenase complex?
|
pyruvate + CoA + NAD+ ---> Acetyl CoA + CO2 + NADH
|
|
|
What are the advantages (3) of multienzyme complexes such as the pyruvate dehydrogenase complex?
|
1: Coordinate control of the enzyme (inhibiting one enzyme will inhibit the complex)2: Substrates travel distance is minimized between the enzymes.3: Intermediates are channeled between successive sites. (related to above)
|
|
|
how does the first enzymatic reaction of the Pyruvate dehydrogenase complex occur?
|
Nucleophilic attack by TPP (from thiamine) on the carbonyl group of pyruvate which leads to removal of CO2 and a remaining 2 carbon molecule attached to TPP. this catalyzed by pyruvate dehydrogenase.
|
|
|
What type of reaction occurs in E1? (2)
|
1: Covalant catalysis2: decarboxylation
|
|
|
Why is the first enzymatic reaction of the Pyruvate dehydrogenase complex irreversible?
|
Because the released CO2 as a gas escapes which renders the revers reaction impossible.
|
|
|
What is the important component of dehydrolipoyl transacetylase in the second reaction of the Pyruvate dehydrogenase complex?
|
The lipoamide arm.
|
|
|
What happens in the second reaction of the Pyruvate dehydrogenase complex?
|
The hydroxyethyl group ( from pyruvate) is reduced to acetic acid and esterified by one of the lipoamide SH groups and creates a thioester bond.
|
|
|
What is the name of the group between the lipoamide disulfide bond and the E2 polypetide backbone?
|
The liposyllysyl arm.
|
|
|
What happens in the third reaction of the Pyruvate dehydrogenase complex?
|
The thioester bond is broken in order to transfer the acyl group ( from pyruvate) to CoA which yields acetyl-CoA.
|
|
|
What are the 3 chemical transformation of pyruvate in the Pyruvate dehydrogenase complex?
|
1: Decarboxylation2: Oxidation of keto group to carboxyl (C2)3: linkage through Thioester bond with CoA
|
|
|
What type of reaction allows the regeneration of lipoamide in E2 by reacting with E3?
|
A disulfide exchange reaction.
|
|
|
How is lipoamide regenerated in E2?
|
It reacts with the FAD of E3 which transfer the S-S bond back to E2 ( FAD has a S-S bond). FAD is inturn oxidize by NAD+ forming two NADHs and returning FAD to the S-S form.
|
|
|
What two enzymes does Arsenic affect ?
|
The Pyruvate dehydrogenase complex and the alphe-ketogluterate dehydrogenase.
|
|
|
Where does Arsenite toxicity come from? ( explain the mechanism)
|
Arsenite can form a bidentate adduct with the disulfide group of lipoamide, effectively blocking its action in the Pyruvate dehydrogenase complex and the alphe-ketogluterate dehydrogenase.
|
|
|
Why is Arsenate so toxic in metabolism?
|
It has an analogus structure to PO4-3, hence it competes in any reactions that involve phosphate.
|
|
|
What enzyme is most affected by arsenate?
|
Glyceraldehyde-3-phosphate dehydrogenase.
|
|
|
What is the net energetic result of glycolysis when poisoned by arsenate (typically)
|
There is no net production of ATP ( or minimal). You use 2 ATP in the reaction but Arsenate will stop the reaction chain at glyceraldehyde-3-phosphate dehydrogenase step which only allows the production of 1 NADH molecule that can lead to a production of either 3 or 2 ATP. Hence, it is non-productive.
|
|
|
Channeling of the metabolic intermediates of an enzymatic complex give rise to two advantages: what are they?
|
1: Side reactions are minimized 2: Protects unstable intermediates ( hence more efficient)
|
|
|
What are the two main enzymes mediating the control of pyruvate metabolism ?
|
Pyruvate dehydrogenase complex and lactate dehydrogenase.
|
|
|
In a nut shell, what is the Warburg effect?
|
Effect where cancer cells inactivate the pyruvate dehydrogenase complex through phosphorylation and forces the conversion of pyruvate to lactate ( anaerobic respiration).
|
|
|
What are the two levels of control for pyruvate dehydrogenase complex?
|
1: Product inhibition ( allosteric inhibition)2: Covalent modification ( phosphorylation)
|
|
|
What are the two products of the pyruvate dehydrogenase complex that inhibits it? How do these products inhibit the complex?
|
Acetyl-CoA and NADH. In excess, they will drive E3 backwards, reducing both Lipoamide and FAD, preventing further enzymatic activity by these sub-units.
|
|
|
Why is it crucial to have a high regulation of the pyruvate dehydrogenase complex?
|
Because the reaction is irreversible and the eukaryotic cell cannot synthesize glucose from acetyl-CoA ( There is no turning back from this point on in the metabolic pathway).
|
|
|
What allosterically activate pyruvate dehydrogenase kinase?
|
NADH and Acetyl-CoA.
|
|
|
What is the targeted sub-unit of the pyruvate dehydrogenase kinase?
|
pyruvate dehydrogenase or E1.
|
|
|
What is the consequence of a high energy charge on the pyruvate dehydrogenase complex?
|
High energy charge induces allosteric and covalent inhibition of the complex.
|
|
|
You find a cell that has a high concentration of m-pyruvate dehydrogenase. What are the most probable concentrations (high or low) of NADH, Acetyl-CoA ? In these circumstances, what would Acetyl-CoA be most likely used for?
|
[NADH] and [Acetyl-CoA] must be very high since pyruvate dehydrogenase is phosphorylated. This means that the cell no longer requires large amounts of energy. Acetyl-CoA could be used for synthesizing fatty acids.
|
|
|
What factors activates pyruvate dehydrogenase phosphatase? Give an example of a source for an increase in concentration in any of these factors.
|
The enzyme is activated by Ca2+ and Md2+. An instance where you could see drastic changes in [Ca2+] is in muscle contraction.
|
|
|
What factors (5) inhibit pyruvate dehydrogenase kinase?
|
Ca2+, Mg2+, pyruvate, ADP and k+.
|
|
|
What does it mean when a system is amphibolic?
|
This means that the system can do both catabolic and anabolic reactions.
|
|
|
What compounds are aerobically catabolized in the citric acid cycle?
|
Carbohydrates, lipids and amino acids.
|
|
|
What does a cataplerotic use of an intermediate in the citric acid cycle mean?
|
it is taken out from the cycle to be used in anabolic reactions.
|
|
|
What is the purpose of an anaplerotic reaction in the citric acid cycle?
|
It is a reaction that replenishes the the depleted intermediates of the citric acid cycle.
|
|
|
What are the three main purposes of the citric acid cycle?
|
1: Produces reducing equivalents (NADH.FADH2) to be oxidized by the electron transport chain.2: Produces organic intermediates for biosynthesis3: Eliminates excess organic compounds as CO2
|
|
|
Pyruvate can be chemically transformed into two intermediates of the citric acid cycle. Which one and through what reaction does the transformation occur?
|
1: Acetyl-CoA through decarboxylation2: Oxaloacetate through carboxylation
|
|
|
Where is the high energy produced in the citric acid cycle stored?
|
It is stored in the reduced state of NAD+ and FAD2+.
|
|
|
What is the final fate of acetyl-CoA in the citric acid cycle?
|
It is oxidized into CO2.
|
|
|
What mode of energy transduction does the citric acid cycle do ?
|
It does non covalent energy transduction. ( meaning that ATP is not directly produced by the cycle).
|
|
|
What is the energetic result of one full turn of the citric acid cycle?
|
It will produce 3 NADH (3 ATP each) 1 FADH2 (2) and 1 GTP. Total of 11 ATP equivalents (12 if you count GTP)
|
|
|
What is characteristic about oxaloacetate in the citric acid cycle?
|
It is regenerated hence it can go multiple rounds of the cycle.
|
|
|
Describe the first reaction of the citric acid cycle ( overall reaction equation).
|
Oxaloacetate + Acetyl-CoA - Citrate synthase-> Citrate
|
|
|
What is unique about the reaction catalyzed by citrate synthase in the citric acid cycle?
|
It is the only reaction that creates a new carbon-carbon bond.
|
|
|
Why is the citrate synthase reaction so exergonic? The fact that this reaction is exergonic implies what?
|
It involves the breaking of a thioester bond which releases a lot of energy. The fact that this is exergonic implies that the reaction is irreversible.
|
|
|
What are the three enzymes involved in irreversible reactions of the citric acid cycle?
|
1: citrate synthase2: Isocitrate dehydrogenase3: alpha-ketogluterate dehydrogenase
|
|
|
What is peculiar about the citric acid cycle's irreversible enzymes' ordering and what does this ordering favour?
|
The three irreversible enzymes are in the first half of the cycle, ensuring directionality of the cycle.
|
|
|
Citryl CoA occurs as a specific stereoisomer. What is its name?
|
S-citryl-CoA.
|
|
|
The attachment point of acyl CoA in citrate is referred by what name?
|
The pro S-arm.
|
|
|
What does Aconitase do in the citric acid cycle?
|
It reversely isomerize citrate into isocitrate.
|
|
|
How many steps is the aconitase reaction and where does the enzyme's name come from?
|
2 step reaction: dehydration followed by a hydration. The intermediate is cis-aconitate, where the enzyme's name comes from.
|
|
|
Labeling oxaloacetate with a carbon 11 allows us to follow its fate. Strangely enough, carbon 11 would always be in CO2 and not a 50 CO2 / 50 in the cycle. What does this imply regarding the enzyme aconitase?
|
Since citrate has two identical carboxymethyl groups, aconitase must be capable of distinguishing the Pro S and Pro R arms of the compound.
|
|
|
What peculiar structure is in Aconitase's active site, which allows the departure of the hydroxy group? Why does OH need help to leave?
|
A iron-sulfur cluster assuming a cubic form. The interaction of an Fe atom and OH allows it to leave because normally OH is a poor leaving group.
|
|
|
Tragically, Matilda died this morning after eating her bowl of cereal. It was later found that fluoroacetate ( compound 1080) was in her breakfast. What happened to poor Matilda?
|
By eating fluoroacetate, she metabolized it into fluorocitrate and this compound blocks the aconitase reaction in the citric acid cycle and it also blocks citrate transport out of the mitochondria.This effectively blocked aerobic respiration and killed Matilda :(.
|
|
|
What is the third reaction of the citric acid cycle? (Describe the enzyme, its products and the steps of the reaction)
|
Isocitrate dehydrogenase will oxidize isocitrate into oxalosuccinate which is still attached to the enzyme. This will produce the first NADH. It then undergoes decarboxylation producing CO2, hence this is IRREVERSIBLE. the product is alpha-ketogluterate.
|
|
|
How are amino acids taken up into the citric acid cycle and metabolised?
|
They are transformed into alpha-ketogluterate and continues the cylce from this point.
|
|
|
What is the fourth reaction of the citric acid cycle? (Describe the enzyme, its products and the steps of the reaction)
|
Alpha-ketogluterate dehydrogenase will do an oxidative decarboxylation on alpha-ketogluterate producing CO2 and NADH . Succinyl-CoA is the final product of the reaction.
|
|
|
Why is the Pyruvate dehydrogenase complex strickingly similar toe alpha-ketogluterate dehydrogenase complex?
|
They both affect their substrate in the same way. (only difference is the substrate really)
|
|
|
What is the equivalent of pyruvate dehydrogenase in the alpha-ketogluterate dehydrogenase complex?
|
Alpha-ketogluterate dehydrogenase.
|
|
|
What is the equivalent of Dihydrolipoyl transacetylase in the alpha-ketogluterate dehydrogenase complex?
|
dihydrolipoyl transsuccinylase.
|
|
|
What is the equivalent of Dihydrolipoyl dehydrogenase in the alpha-ketogluterate dehydrogenase complex?
|
its the same enzyme in the complex.
|
|
|
Is there an equivalent of Pyruvate dehydrogenase kinase and phosphatase in the alpha-ketogluterate dehydrogenase complex? What is the reason for that?
|
There isn't. This is probably due to the fact that alpha-ketogluterate dehydrogenase is not as a pivotal reaction as pyruvate dehydrogenase in terms of "commitment". Acetyl-CoA cannot be converted back to glucose but pyruvate can, which is why the pyruvate dehydrogenase complex needs that extra regulation.
|
|
|
What is a synonym of succinyl CoA synthetase?
|
succinate thiokinase.
|
|
|
What happens in the reaction catalyzed by succinyl CoA synthetase ?
|
Succinyl CoA synthetase will break the thioester bond of CoA and will transfer the high energy in a P-P bond to form GTP from GDP.
|
|
|
What is the mode of energy transfer in the reaction of Succinyl CoA synthetase?
|
The free energy is transferred through a covalent energy transduction mode.
|
|
|
Describe how the covalent energy transduction occurs in the succinyl CoA synthetase reaction. (3 steps)
|
1: Phosphate will replace CoA in succinate. the energy will be conserved through the bond transfer.2: Histidine in the enzyme will pick up the phosphate in succinate.3: GDP will then attack the phosphate on histidine, creating GTP.
|
|
|
How is GTP converted to ATP?
|
GTP+ADP -nucleoside diphosphate kinase-> ATP+GDP
|
|
|
What does succinate dehydrogenase do?
|
It will catalyze the oxidation of succinate. This will generate FADH2 and fumerate.
|
|
|
Succinate dehydrogenase is part of what important complex of the mitochondria?
|
Complex 2 of the electron transport chain.
|
|
|
You examine your little rat called Stewart. You're astonished to find a high concentration of cis-fumerate in his mitochondrial tissue. What enzyme is wrong in stewart's metabolism?
|
Stewart's succinate dehydrogenase is malfunctioning as it usually has a stereospecificity to oxidize succinate in a trans structure, not cis.
|
|
|
Why FAD in succinate dehydrogenase can't leave the enzyme like it usually can once reduced?
|
Because it is covalently bound to histidine residue in succinate dehydrogenase.
|
|
|
You design a compound that can aggregate a protein that has a similar structure to succinate dehydrogenase. You inject it in the mitochondrial matrix and find that no aggregates of the enzyme is found there. Why?
|
Succinate dehydrogenase is bound to the inner mitochondrial membrane, as it is part of complex 2. Hence the enzyme can's aggregate in the matrix.
|
|
|
What is interesting about malonate's structure and what can it do consequently to that ?
|
Malonate has an anologus structure to succinate and hence can inhibit Succinate dehydrogenase.
|
|
|
How can you prove that the citric acid cycle is actually a cycle?
|
Feed a mitochondria with fumerate and inject malonate in it as well. Malonate is an inhibitor of succinate dehydrogenase for both the forward and backward reaction. If you find an increase in concentration of succinate (the substrate of the enzyme) and a decrease in concentration of fumerate ( the product) , it suggests that the compounds undergo a cylce.
|
|
|
What does fumerase do?
|
catalyzes the hydration of fumerate.
|
|
|
Describe the reaction catalyzed by malate dehydrogenase.
|
Will oxidize malate into oxaloacetate producing the final NADH of the cycle.
|
|
|
Malate dehydrogenase reaction is highly endergonic. How does this reaction proceed in normal conditions?
|
Through the pairing of the reaction with the highly exergonic reaction of citrate synthase which pulls the synthesis of oxaloacetate forward.
|
|
|
You discovered a new protein that you called zombierate. A chronic exposure to the R-confirmation of this protein affects the nervous system inducing aggressive and relentless behavior. The R-confirmation of the protein is however very unstable and spontaneously return to the T-confirmation. Zombierate is allosterically controlled by oxaloacetate. Oxaloacetate being always present in the mitochondria, why haven't we witnessed the first season of Walking Dead yet?
|
Because oxaloacetate is produced by a reaction that is highly endogonic and is immediately processed by a highly exergonic ( spontaneous) reaction. This means that [oxaloacetate] is very low and presumably not high enough to maintain [R-zombierate] high enough for us to fell its effects.
|
|
|
Why do we say that citrate has a prochiral center?
|
Citrate does not seem to have an asymmetric carbon but it behaves as if it had one.
|
|
|
What does a planer molecule with no rotational symmetry has as a characteristic?
|
They are prochiral
|
|
|
What phenomenon causes the prochirality of citrate and why does this phenomenon happen?
|
The attack of acetyl-CoA is always on the si face of oxaloacetate. Meaning that the pro S arm of citrate ALWAYS comes from acetyl-CoA. This phenomenon always happens because of the way oxaloacetate is bound to the active site of citrate synthase.
|
|
|
You managed to create a species of macro phage that target cancer cells specifically. However the mutation also made it such that malate dehydrogenase is half as efficient in a normal cell and you find your macrophages not doing so well. What could you possibly do to save your macrophages and maybe, just maybe, find a cure for cancer?
|
Because malate dehydrogenase is not very good at its job, a constant feed of oxaloacetate should be fed to these macrophages. A compound that degrades malate could also be introduced to avoid malate accumulation. This could keep the citric acid cycle going and keep the macrophages alive.
|
