Metabolism Flashcards
Ethanol metabolism
FOMEpizole—inhibits alcohol dehydrogenase and is an antidote For Overdoses of Methanol or Ethylene glycol.
Disulfiram—inhibits acetaldehyde dehydrogenase (acetaldehyde accumulates, contributing to hangover symptoms), discouraging drinking.
NAD+ is the limiting reagent.
Alcohol dehydrogenase operates via zero-order kinetics.
Ethanol metabolism increase NADH/NAD+ ratio in liver, causing:
Pyruvate -> lactate (lactic acidosis)
Oxaloacetate -> malate (prevents gluconeogenesis -> fasting hypoglycemia)
Dihydroxyacetone phosphate -> glycerol3-phosphate (combines with fatty acids to make triglycerides -> hepatosteatosis)
End result is clinical picture seen in chronic alcoholism.
Additionally, increased NADH/NAD+ ratio disfavors TCA production of NADH ->increased utilization of acetyl-CoA for ketogenesis (for ketoacidosis) and lipogenesis (for hepatosteatosis)
Mitochondria
Fatty acid oxidation (β-oxidation), acetylCoA production, TCA cycle, oxidative phosphorylation, ketogenesis
Cytoplasm
Glycolysis, HMP shunt, and synthesis of steroids (SER), proteins (ribosomes, RER), fatty acids, cholesterol, and nucleotides
Mitochondria & Cytoplasm
Heme synthesis, Urea cycle, Gluconeogenesis
HUGs take two (ie, both
Kinase
Catalyzes transfer of a phosphate group from a high-energy molecule (usually ATP) to a substrate (eg, phosphofructokinase).
Phosphorylase
Adds inorganic phosphate onto substrate without using ATP (eg, glycogen phosphorylase)
Phosphatase
Removes phosphate group from substrate (eg, fructose-1,6-bisphosphatase)
Dehydrogenase
Catalyzes oxidation-reduction reactions (eg, pyruvate dehydrogenase)
Hydroxylase
Adds hydroxyl group (−OH) onto substrate (eg, tyrosine hydroxylase)
Carboxylase
Transfers CO2 groups with the help of biotin (eg, pyruvate carboxylase)
Mutase
Relocates a functional group within a molecule (eg, vitamin B12–dependent methylmalonyl-CoA mutase).
Synthase/synthetase
Combines 2 molecules into 1 (condensation reaction) either using an energy source (synthase, eg, glycogen synthase) or not (synthetase, eg, PRPP synthetase)
Glycolysis
CONTROL ENZYME:
Phosphofructokinase-1 (PFK-1)
REGULATORS:
AMP ⊕, fructose-2,6-bisphosphate ⊕
ATP ⊝, citrate⊝
Gluconeogenesis
CONTROL ENZYME:
Fructose-1,6-bisphosphatase
REGULATORS:
Citrate ⊕
AMP ⊝, fructose-2,6-bisphosphate ⊝
TCA cycle
CONTROL ENZYME:
Isocitrate dehydrogenase
REGULATORS:
ADP ⊕
ATP ⊝, NADH ⊝
Glycogenesis
CONTROL ENZYME:
Glycogen synthase
REGULATORS:
Glucose-6-phosphate ⊕, insulin ⊕, cortisol ⊕
Epinephrine ⊝, glucagon⊝
Glycogenolysis
CONTROL ENZYME:
Glycogen phosphorylase
REGULATORS:
Epinephrine ⊕, glucagon ⊕, AMP ⊕
Glucose-6-phosphate ⊝, insulin⊝, ATP ⊝
HMP shunt
CONTROL ENZYME:
Glucose-6-phosphate dehydrogenase (G6PD)
REGULATORS:
NADP+ ⊕
NADPH ⊝
De novo pyrimidine synthesis
CONTROL ENZYME:
Carbamoyl phosphate synthetase II
REGULATORS:
ATP ⊕, PRPP ⊕
UTP ⊝
De novo purine synthesis
CONTROL ENZYME:
Glutamine-phosphoribosylpyrophosphate (PRPP) amidotransferase
REGULATORS:
AMP ⊝, inosine monophosphate (IMP) ⊝, GMP ⊝
Urea cycle
CONTROL ENZYME:
Carbamoyl phosphate synthetase I
REGULATORS:
N-acetylglutamate ⊕
Fatty acid synthesis
CONTROL ENZYME:
Acetyl-CoA carboxylase (ACC)
REGULATORS:
Insulin ⊕, citrate ⊕
Glucagon ⊝, palmitoyl-CoA ⊝
Fatty acid oxidation
CONTROL ENZYME:
Carnitine acyltransferase I
REGULATORS:
Malonyl-CoA ⊝
Ketogenesis
CONTROL ENZYME:
HMG-CoA synthase
Cholesterol synthesis
CONTROL ENZYME:
HMG-CoA reductase
REGULATORS:
Insulin ⊕, thyroxine ⊕
Glucagon ⊝, cholesterol⊝
ATP production
Aerobic metabolism of glucose produces 32 net ATP via malate-aspartate shuttle (heart and liver), 30 net ATP via glycerol-3-phosphate shuttle (muscle).
Anaerobic glycolysis produces only 2 net ATP per glucose molecule.
ATP hydrolysis can be coupled to energetically unfavorable reactions.
Arsenic causes glycolysis to produce zero net ATP.
Activated carriers
ATP -> Phosphoryl groups
NADH, NADPH, FADH2 -> Electrons
CoA, lipoamide -> Acyl groups
Biotin -> CO2
Tetrahydrofolates -> 1-carbon units
S-adenosylmethionine (SAM) -> CH3 groups
TPP -> Aldehydes
Universal electron acceptors
Nicotinamides (NAD+ from vitamin B3, NADP+) and flavin nucleotides (FAD+ from vitamin B2).
NAD+ is generally used in catabolic processes to carry reducing equivalents away as NADH.
NADPH is used in anabolic processes (steroid and fatty acid synthesis) as a supply of reducing equivalents.
NADPH is a product of the HMP shunt.
NADPH is used in: Anabolic processes Respiratory burst Cytochrome P-450 system Glutathione reductase
Hexokinase vs glucokinase
HEXOKINASE
- Most tissues, except liver and pancreatic β cells
- low Km (high affinity)
- low Vmax (low capacity)
- not induced by insulin
- feedback inhibited by G6P
GLUCOKINASE
- Liver, β cells of pancreas
- high Km (low affinity)
- high Vmax (high capacity)
- induced by insulin
- feedback not inhibited by G6P
