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42 Cards in this Set

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Where does the pentose phosphate pathway occur in cells?
in the cytoplasm
What is the purpose of the pentose phospate pathway?
to create NADPH and pentoses (including ribose 5-phosphate, which can be used in DNA/RNA synthesis)
What 2 main phases is the pathway divided into, and what do these distinct phases produce?
-2 phases: one oxidative, then one non-oxidative.
-Oxidative: makes NADPH. Non-oxidative makes pentoses (interconversion of sugars from the six carbon glucose to a five carbon pentose)
One major utility of the pentose phosphate pathway is the creation of NADPH. NADPH can be used by the body for...
1. SYNTHESIS of fatty acids, cholesterol, steroid hormones/neurotransmitters, bile salts, nucleotides
2. DETOXIFICATION:
a. cytochrome p450 monooxygenases, enzymes that metabolize drugs
b. reduction of oxidized glutathione (mostly in RBCs)
The ratio of NADPH to NADP is in favor of ___________. Why?
-in favor of NADPH

-NADPH is used extensively in cells to reduce things (this synthesizes fatty acids and detoxifies stuff)
The ratio of NAD+ to NADH is in favor of _______. Why?
-NAD+
-NAD+ is used extensively in cells as an oxidizing agent that accepts electrons (electron transport chain)
NAD/NADH is used in what pathway, pentose phosphate or glycolysis?
glycolysis
How does NADPH regulate the pentose phosphate pathway?
It is an allosteric inhibitor of glucose-6-phosphate dehydrogenase (enzyme acting on the first step of the pathway)
In the oxidative phase of the pentose phosphate pathway, the first step involves glucose 6-phosphate. What enzyme oxidizes glucose 6-phosphate, and what are the two byproducts?
-glucose 6 phosphate dehydrogenase. Since G6P is being oxidized, the coenzyme NADP+ has to be REDUCED into NADPH.

-6-Phosphogluconolactone
In the third step of the oxidative phase, 6-phosphogluocnate is oxidized with the enzyme _________________ into what three products?
-6-phosphogluconate dehydrogenase

-makes NADPH, CO2, and ribulose -5-phosphate
A dehydrogenase enzyme does what?
It oxidizes stuff (think dehydro--removing hydrogen--it's the same as oxidizing something)
When a dehydrogenase enzyme is involved in this pathway, what coenzyme is usually produced?
NADPH
What are the net products of the oxidative phase?
-2 NADPH
-complete oxidation of glucose-6-phosphate into ribulose-5-phosphate
-CO2
In the non-oxidative stage of the pathway, ribulose-5-phosphate is converted to _______________ using the ___________ enzyme.
-ribose-5-phosphate

-ribulose-5-phosphate isomerae
RibUlose-5-phosphate is converted into ribose-5-phosphate to be used in the synthesis of...
ATP and ribonucloetides (DNA and RNA)
When the cell is actively dividing, ribose-5-phosphate is used for...
to make ribonucleotides for DNA/RNA
When the cell is not actively dividing, ribose-5-phosphate is used primarily...
for glycolysis to make ATP. Ribose-5-phosphate can be turned into fructose-6-phosphate or glyceraldehdye-3-phosphate, intermediates of glycolysis, which can then be used to make ATP.
Epimerase converts ribulose-5-phosphate to...
xylulose-5-phosphate
Transketolases convert...
-ribose-5-phosphate to sedoheptulose 7-phosphate

-xylulose 5-phosphate to glyceraldehyde 3-phosphate (GAP)

-erythrose 4-phosphate to fructose 6-phosphate
Transaldolase converts...
-GAP to fructose 6-phosphate

-sedoheptulose 7-phosphate to erythrose 4-phosphate
Glycolysis causes what kind of stress? How is this stress counteracted?
-oxidative stress

-oxidative stress is counteracted by producing more NADPH. NADPH reduces the oxidated species. This causes the fructose 6-phosphate from the pentose phosphate pathway to be converted back to glucose 6-phosphate instead of allowing it to continue to glycolysis, because, of course, glycolysis causes more oxidative stress!
When you have a lot of oxidative stress, what do you really need?
NADPH!
Oxidative stress can be increased due to...
1. drug induced hemolytic anemia (you don't have oxygen because your red blood cells have died, so instead you go through lactic acid fermentation, increasing oxidative stress)

2. reaction of Hb with O2 causes free radicals

3. Fava beans

4. Infections
Inert molecular oxygen (O2) is activated by
-Metalloproteins (hemoglobin and myoglobin)
-metalloenzymes (oxidases, oxygenases)
What do oxidases do?
enzymes that use oxygen to accept hydrogen (oxidize stuff)
What do oxygenases do?
degrade aromatic amino acids
What does the activation of molecular oxygen create?
reactive oxygen species (ROS)...these reactive oxygen species, like H2O2, generate free radicals (like OH-).
In phagocytosis, NADPH from the pentose phosphate pathway is used to create __________ and _________, which can be used to kill what is being phagocytosed (like bacteria). These reactive oxygen species degrade ________________.
-H2O2

-HOCl (hypochlorus acid)

- bacterial proteins, lipids, and DNA.
When the enzyme __________ reacts with O2 in hemoglobin, what is produced?
-xanthine oxidase

-produce superoxide dimutase and hydrogen peroxide
When hemoglobin reacts with O2, it forms reactive oxygen species that can damage hemoglobin, creating _____________.
-MetHb
The aggregation of MetHb forms...
Heinz-bodies
The reaction of reactive oxygen species (H2O2 and superoxide dimutase) with iron create _________ and __________. These species do what to the cell membrane?
free radicals, including OH* and reactive Fe

-the above damage lipids and proteins of the membrane, which causes altered ion channels, which then causes cell death
What causes aging?
oxidative damage of DNA through free radicals
What causes skin cancer?
oxidative damage through the creation of ROS from UV light
How does NADPH protect RBC from oxidative stress caused by ROS?
It maintains glutathione (GSH) in a reduced state
GSH is important so that H2O2 can be reduced. What enzyme reduces H2O2 in the presence of glutathione (GSH)?
glutathione peroxidase, containing SELENIUM in its active site
When you have a glucose-6-dehydrogenase deficiency ("Favism"), oxdiative stress by way of ________, ________, _________, and ________ can be lethal because what pathway is inhibited?
-fava beans, infections, drugs, regular interaction between O2 and Hb causing free radicals

-the production of NAPDH is hindered, which makes it so GSH can't be reduced, which makes it so that GSH-peroxidase is non-functional...when GSH-peroxidase is non-functional, ROS like H2O2 cannot be reduced. The resultant accumulation of ROS > free radicals causes DEATH.
What is necessary to synthesize glutathione?
-cysteine and glycine
-2 ATP
A deficiency in glucose 6 phosphate dehydrogenase confers an evolutionary advantage against...
malaria because the RBC can't stay alive long enough because it's reactive species defense mechanisms are non-existent
Transketolases use ______________ as a cofactor.
thiamine
The first NADPH in the pentose phosphate pathway is made when
glucose 6 phosphate is converted to 6-phosphogluconolactone via glucose 6 phosphate dehydrogenase
The 2nd and last NADPH in the pentose phsophate pathway is made when
6-phosphogluconate is converted to ribulose 5-phosphate via 6-phosphogluconate dehydrogenase (last step of the oxidative reactions in the pathway)