Biochem Ch 21

Front 1

Three stages of catabolism

Back 1

1. production of Acetyl CoA via
fatty acids
lysine and leucine
carbohydrates (glucose -->
pyruvate --> acetyl CoA)

2. oxidation of Acetyl CoA to yield 3NADH and FADH2

3. e- transfer down electron transport chain and oxidative phosphorylation.(via phosphorylation of ADP --> ATP)

Front 2

Why the TCA cycle is the hub of metabolism.

Back 2

it is the point at which the metabolism of all major fuels converge.

Front 3

The three kinds of subunits of the pyruvate dehydrogenase complex: know how they participate in the reaction.

Back 3

Reaction 1 - pyruvate dehydrogenase-TPP --> decarboxylates pyruvate, yielding hydroxyethyl-TPP

Reaction 2 - pyruvate dehydrogenase-lipoic acid (covalently linked to Lys on E2 (lipoamide) - accepts hydroxyethyl from TPP in the form of an acetyl group forming acetyl-dihydrolipoamide

Reaction 3 - dihydrolipoyl transacetylase-CoA - accept acetyl group from acetyl-dihydrolipoamide generating acetyl CoA and dihydrolipoamide.

Reaction 4 - dihydrolipoyl dehydrogenase-FAD - reduced by dihydrolipoamide

Reaction 5 - dihydrodehydrogenase-NAD+ - reduced by FADH2

Front 4

How does a single lipollysyl arm carry out all the three reactions in which it participates

Back 4

A single lipollysyl arm on E2 cannot swing all the way between participating sites on E1 and E3. The problem is solved through the participation of at least two lipollysyl arms on each E2, with the transfer of the acetyl group from one arm to the next.

Front 5

Reasons why thioester bonds are high-energy bonds; the bond that is cleaved when a thioester participates in a nucleophillic displacement reaction.

Back 5

lack of resonance stabilization is the basis for the higher delta G of hydrolysis of thioesters, relative to that of ordinary esters.

Resonance stabilization of ordinary esters involves pi-electron overlap, giving partial double bond character to the C-O bond. In thioesters, the large atomic size of S reduces the pi-electron overlap between C and S, so that the C-S link does not contribute to the resonance stabilization. Thus, thioesters are destabilized relative to esters, so that the delta G of hydrolysis is increased. Furthermore, the lack of resonance stabilization makes the C-S bond weaker than the corresponding C-O bond, thus making R-S- a good leaving group in a nucleophillic displacement reactions.

Front 6

Which reactions of the TCA cycle are accompanied by large negative free energy changes?

Back 6

acetyl-CoA + oxaloacetate --> citrate

isocitrate --> alpha keto-glutarate

alpha-ketoglutarate --> succinyl-CoA

Front 7

Role of the iron-sulfur cluster of aconitase in catalysis

Back 7

The iron-sulfure center participates in dehydration and rehydration (see Figure 21-20 for details).

Front 8

Sum of the TCA cycle reactions

Back 8

Acetyl Co-A + 3NAD+ + FAD + 2 H2O + GDP + Pi --> 2CO2 + 3 NADH + FADH2 + 2H+ + GTP + CoA

Front 9

Pathways that utilize TCA cycle intermediates

Back 9

a. gluconeogenesis utilizes malate that has been transported across the mitochondrial membrane into the cytosol.

b. lipid biosynthesis utilizes cytosolic Acetyl CoA which is generated by the breakdown of citrate (which can cross the mitochondrial membrane).

c. alpha ketoglutarate used to synthesize glutamate. oxaloacetate used to synthesize aspartate.

d. Porphyrin biosynthesis utilizes succinyl CoA as a starting material.

Front 10

Reactions that replenish TCA cycle intermediates; which one is the most important?

Back 10

pyruvate + CO2 + ATP + H2O --> oxaloacetate + ADP + Pi (most important)

transamination and deamination of most amino acids leads to the production of alpha-ketoglutarate and oxaloacetate.

breakdown of some amino acids leads to the production of succinyl CoA

oxidation of some odd-chain fatty acids leads to the production of succinyl CoA (occurring in the mitochondria).

in plants, yeast, and bacteria, PEP is converted to oxaloacetate by PEP carboxylase

PEP + HCO3 --> oxaloacetate + Pi

NOTE: neither an energy cofactor nor biotin is required b/c PEP is an energy-rich compound

Reductive carboxylation of pyruvate by malic enzyme to yield L-malate (occurring in the cytosol)

pyruvate + HCO3 + NADPH + H+ --> reductive carboxylation) --> L-malate + NADP+

Front 11

why is citrate a prochiral molecule? How does aconitase distinguish b/w the two symmetrical methylcarboxyl groups of citrate?

Back 11

It is prochiral so that it can bind to an asymmetric enzyme (even though the molecule itself is symmetric).

the enzyme can distinguish b/w the two methylcarboxyl groups b/c they are sterically non-equivalent even though they are stereochemically equivalent. see textbook.