Metabolism

Question 1

Ethanol metabolism

Answer 1

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: ƒ
Pyruvate -> lactate (lactic acidosis) ƒ
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)

Question 2

Mitochondria

Answer 2

Fatty acid oxidation (β-oxidation), acetylCoA production, TCA cycle, oxidative phosphorylation, ketogenesis

Question 3

Cytoplasm

Answer 3

Glycolysis, HMP shunt, and synthesis of steroids (SER), proteins (ribosomes, RER), fatty acids, cholesterol, and nucleotides

Question 4

Mitochondria & Cytoplasm

Answer 4

Heme synthesis, Urea cycle, Gluconeogenesis

HUGs take two (ie, both

Question 5

Kinase

Answer 5

Catalyzes transfer of a phosphate group from a high-energy molecule (usually ATP) to a substrate (eg, phosphofructokinase).

Question 6

Phosphorylase

Answer 6

Adds inorganic phosphate onto substrate without using ATP (eg, glycogen phosphorylase)

Question 7

Phosphatase

Answer 7

Removes phosphate group from substrate (eg, fructose-1,6-bisphosphatase)

Question 8

Dehydrogenase

Answer 8

Catalyzes oxidation-reduction reactions (eg, pyruvate dehydrogenase)

Question 9

Hydroxylase

Answer 9

Adds hydroxyl group (−OH) onto substrate (eg, tyrosine hydroxylase)

Question 10

Carboxylase

Answer 10

Transfers CO2 groups with the help of biotin (eg, pyruvate carboxylase)

Question 11

Mutase

Answer 11

Relocates a functional group within a molecule (eg, vitamin B12–dependent methylmalonyl-CoA mutase).

Question 12

Synthase/synthetase

Answer 12

Combines 2 molecules into 1 (condensation reaction) either using an energy source (synthase, eg, glycogen synthase) or not (synthetase, eg, PRPP synthetase)

Question 13

Glycolysis

Answer 13

CONTROL ENZYME:
Phosphofructokinase-1 (PFK-1)

REGULATORS:
AMP ⊕, fructose-2,6-bisphosphate ⊕
ATP ⊝, citrate⊝

Question 14

Gluconeogenesis

Answer 14

CONTROL ENZYME:
Fructose-1,6-bisphosphatase

REGULATORS:
Citrate ⊕
AMP ⊝, fructose-2,6-bisphosphate ⊝

Question 15

TCA cycle

Answer 15

CONTROL ENZYME:
Isocitrate dehydrogenase

REGULATORS:
ADP ⊕
ATP ⊝, NADH ⊝

Question 16

Glycogenesis

Answer 16

CONTROL ENZYME:
Glycogen synthase

REGULATORS:
Glucose-6-phosphate ⊕, insulin ⊕, cortisol ⊕
Epinephrine ⊝, glucagon⊝

Question 17

Glycogenolysis

Answer 17

CONTROL ENZYME:
Glycogen phosphorylase

REGULATORS:
Epinephrine ⊕, glucagon ⊕, AMP ⊕
Glucose-6-phosphate ⊝, insulin⊝, ATP ⊝

Question 18

HMP shunt

Answer 18

CONTROL ENZYME:
Glucose-6-phosphate dehydrogenase (G6PD)

REGULATORS:
NADP+ ⊕
NADPH ⊝

Question 19

De novo pyrimidine synthesis

Answer 19

CONTROL ENZYME:
Carbamoyl phosphate synthetase II

REGULATORS:
ATP ⊕, PRPP ⊕
UTP ⊝

Question 20

De novo purine synthesis

Answer 20

CONTROL ENZYME:
Glutamine-phosphoribosylpyrophosphate (PRPP) amidotransferase

REGULATORS:
AMP ⊝, inosine monophosphate (IMP) ⊝, GMP ⊝

Question 21

Urea cycle

Answer 21

CONTROL ENZYME:
Carbamoyl phosphate synthetase I

REGULATORS:
N-acetylglutamate ⊕

Question 22

Fatty acid synthesis

Answer 22

CONTROL ENZYME:
Acetyl-CoA carboxylase (ACC)

REGULATORS:
Insulin ⊕, citrate ⊕
Glucagon ⊝, palmitoyl-CoA ⊝

Question 23

Fatty acid oxidation

Answer 23

CONTROL ENZYME:
Carnitine acyltransferase I

REGULATORS:
Malonyl-CoA ⊝

Question 24

Ketogenesis

Answer 24

CONTROL ENZYME:

HMG-CoA synthase

Question 25

Cholesterol synthesis

Answer 25

CONTROL ENZYME: HMG-CoA reductase REGULATORS: Insulin ⊕, thyroxine ⊕ Glucagon ⊝, cholesterol ⊝

Question 26

ATP production

Answer 26

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.

Question 27

Activated carriers

Answer 27

ATP -> Phosphoryl groups NADH, NADPH, FADH2 -> Electrons CoA, lipoamide -> Acyl groups Biotin -> CO2 Tetrahydrofolates -> 1-carbon units S-adenosylmethionine (SAM) -> CH3 groups TPP -> Aldehydes

Question 28

Universal electron acceptors

Answer 28

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: ƒ Anabolic processes Respiratory burst Cytochrome P-450 system Glutathione reductase ```

Question 29

Hexokinase vs glucokinase

Answer 29

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