Metabolism

aerobic metabolism:
32 ATP via malate-aspartate shuttle (heart and liver)

30 ATP via glycerol-3-phosphate shuttle (muscle)

Anaerobic:
2 ATP per glucoes

ATP

NADH, NADPH, FADH2

NAD+: catabolic processes to carry reducing equivalens away as NADH

NADPH: anabolic processes (steroid and FA synthesis) to supply reducing equivalents

used in:
GARP those reducing equivalents!:
Glutathione reductase (antioxidant)
Anabolic
Respiratory burst (macs)
P450

CoA, lipoamide

biotin

tetrahydrofolates

SAM

TPP

1st step in glycolysis and glycogen synthesis (in liver)
**phosphorylation of glucose --> G6P

Hexokinase: ubiquitous
high affinity (low Km), low capacity (low Vmax); uninduced by insulin
-feedback inhibition by G6P

GLucokinase:
Liver and beta cells of pancreas
Low affinity (high Km)
High capacity (high Vmax)
**so liver only STORES extra glucose
-induced by insulin
GLUcokinase is a GLUtton

Inhibitory:
G6P
ATP
Citrate
Alanine
NADH
Acetyl-CoA

Stimulatory:
AMP
F26BP
F16BP

Fed State:
Insulin --> decreased cAMP --> decreased PKA --> activate PFK2 (inactivate FBPase2)

PFK2 makes F26BP, which stimulates PFK1 to make F16BP for GLYCOLYSIS

Fasting state:
Glucagon --> increase cAMP --> increase PKA --> activate FBPase2 (inactive PFK2)

increases F6P for use in GLUCONEOGENSIS

Converts Pyruvate --> Acetyl-CoA for TCA cycle

Requires 5 cofactors: TLC for No one
TPP (thiamine pyrophosphate)
Lipoic acid (inhibited by Arsenic)
CoA
FAD
NAD

*makes 1NADH + CO2
*activated by exercise:
ADP, Ca, NAD > NADH

**alpha-ketoglutarate DH complex has same cofactors
-converts alpha-ketoglutarate --> succinyl-CoA (TCA cycle)

per acetyl-CoA: 12ATP (24ATP per glucose)
3 NADH
1 FADH2
2 CO2
1 GTP

NADH electrons enter mitochondria via malate-aspartate (heart & liver) or glycerol-3-phosphate shuttle (muscle)

delta G = delta H - T*delta S

Gibbs free energy = change in heat(energy) - temp*entropy

Endergonic rxn: takes in energy
Exergonic rxn: releases energy (favorable, spontaneous)

Level of exergonicity:
PEP: -62kJ/mol
ATP: -31
AMP: -14

TCA - ICA
1. Citrate synthase
2. Isocitrate DH (rate-limiting)
3. alpha-KG DH

makes ATP in electron transport chain
1NADH --> 3ATP
1 FADH2 --> 2 ATP bc enters complex II, which is succinate DH) (lower energy level than NADH- complex I)

ARM A CAtCH
Complex I:
Amytal
Rotenone (insecticide)
MPP (MPTP deriv)

Complex III:
1. antimycin A (fish poison)

Complex IV:
CO
Azide: N3-
CN-
H2S

Increases proton gradient, but electron transport stops, so no ATP is produced

Oligomycin:
macrolide made by streptomyces

Take 2 Aspirin for my fever (thermogenin)

Increase permeability of membrane, causing drop in proton gradient and increased O2 consumption
ATP synthesis stops but electron transport continues
*produces heat

2,4-Dinitrophenylhydralazine (DNP) = wood preservative

Aspirin
Thermogenin

PPFG:
mito, cytosol, cytosol, ER
1. Pyruvate carboxylase: mito
-req. biotin, ATP; activated by acetyl-CoA
2. PEP carboxykinase: cytosol
-req GTP
3. F16BPase: cytosol
4. Glucose-6-phosphatase: ER
(def: VonGierke's)

-occurs in liver (a little in kidney, intestine)
-Def --> hypoglycemia

yield 1 propionyl-CoA --> Methylmalonyl-CoA --> Succinyl-CoA

*enters TCA cycle and can be used for gluconeogenesis

*even chain: yield acetyl-CoA (so no GNG)

per acetyl-CoA: 12ATP (24ATP per glucose)
3 NADH
1 FADH2
2 CO2
1 GTP

NADH electrons enter mitochondria via malate-aspartate (heart & liver) or glycerol-3-phosphate shuttle (muscle)

delta G = delta H - T*delta S

Gibbs free energy = change in heat(energy) - temp*entropy

Endergonic rxn: takes in energy
Exergonic rxn: releases energy (favorable, spontaneous)

Level of exergonicity:
PEP: -62kJ/mol
ATP: -31
AMP: -14

TCA - ICA
1. Citrate synthase
2. Isocitrate DH (rate-limiting)
3. alpha-KG DH

makes ATP in electron transport chain
1NADH --> 3ATP
1 FADH2 --> 2 ATP bc enters complex II, which is succinate DH) (lower energy level than NADH- complex I)

ARM A CAtCH
Complex I:
Amytal
Rotenone (insecticide)
MPP (MPTP deriv)

Complex III:
1. antimycin A (fish poison)

Complex IV:
CO
Azide: N3-
CN-
H2S

Increases proton gradient, but electron transport stops, so no ATP is produced

Oligomycin:
macrolide made by streptomyces

Take 2 Aspirin for my fever (thermogenin)

Increase permeability of membrane, causing drop in proton gradient and increased O2 consumption
ATP synthesis stops but electron transport continues
*produces heat

2,4-Dinitrophenylhydralazine (DNP) = wood preservative

Aspirin
Thermogenin

PPFG:
mito, cytosol, cytosol, ER
1. Pyruvate carboxylase: mito
-req. biotin, ATP; activated by acetyl-CoA
2. PEP carboxykinase: cytosol
-req GTP
3. F16BPase: cytosol
4. Glucose-6-phosphatase: ER
(def: VonGierke's)

-occurs in liver (a little in kidney, intestine)
-Def --> hypoglycemia

yield 1 propionyl-CoA --> Methylmalonyl-CoA --> Succinyl-CoA

*enters TCA cycle and can be used for gluconeogenesis

*even chain: yield acetyl-CoA (so no GNG)

Provide a source of NADPH from abundantly available G6P
-used for reductive reactions, esp in RBCs

sites: aLARM
Liver
Adrenal cortex
RBCs
Mammary glands
(sites of FA and steroid synthesis, where NADPH is needed for anabolic rxn)

Oxidative: irreversible
G6P ---G6PD---> 2NADPH, CO2, Ribulose-5-P (PRPP precursor for nucletide synthesis)

Nonoxidative: reversible
RIbulose-5-P ---transketolases, B1 ----> Ribose-5-P, G3P, F6P

Activation of membrane-bound NADPH oxidase (pmns, macs) --> rapid release of ROIs for immune response

bypasses rate-limiting step of glycolysis (PFK)

-creates DHAP & Glyceraldehyde --> G3P --> Glycolysis

beta-galactosidase

lactose = galactosyl beta-1,4-glucose

Traps glucose in cell by converting it to sorbitol

Converts sorbitol to Fructose

*schwann cells, lens, retina, kidneys don't have this, so accumulate sorbitol --> osmotic damage

sxs: cataracts, retinopathy, peripheral neuropathy see in DM

**liver, ovaries, seminal vesicles have both enzymes

Excess nitrogen converted to urea and excreted by kidneys

Urea: CO2 + NH4 + nitrogen from Aspartate

CPS1: to make carbamoyl phosphate

Ornithine transcarbamoylase: makes citrulline from carbamoyl phosphate and ornithine

By Alanine, glutamate (and glutamine)

alpha-ketoglutarate accepts NH3 from amino acids --> glutamate