Glycogen, TCA Cycle and Mitochondria (Lecture 10)

Question 1

citric acid cycle

Answer 1

series of 8 enzymatic reactions that combine acetyl coa with oxaloacetate in order to generate CO2, NADH and FADH2 and regenerate the starting products of oxaloacetate

Question 2

CAC is part of

Answer 2

aerobic glycolysis but does directly consume O2

Question 3

how is CAC amphibolic

Answer 3

site of anabolism and catabolism

ANABOLISM:
CAC intermediates are the starting starting points of anabolic pathways (gluconeogenesis, FA synthesis, AA synthesis)

these are catapleyrotic reactions as for they deplete the pool of CAC intermediates

CATABOLISM:
CAC intermediates are the end point of catabolic pathways . the aerobic catabolism of carbohydrates, lipids and amino acids merge into the CAC (oxaloacetate from pyruvate carboxylase, AA degradation)

these are anapleurotic reaction, as for they replenish the depleted CAC intermediates

Question 4

3 main functions of CAC

Answer 4

produce reducing equivalents in the for of NADH and FADH2 (these are e- carrying molecules that can donate their e- to the ETC)

produce intermediates for the biosynthesis of:
citrate –> fatty acids
alpha keto glutarate –> amino acids

removed carbon form the metabolite

Question 5

does CAC generate energy

Answer 5

yes via reducing equivalents and 1 GTP is also formed

Question 6

overall reaction of CAC shows that it generates

Answer 6

3 NADH FADH2 GTP CO2 CoA

Question 7

what confers directionality

Answer 7

3 committing steps:

citrate synthase (acetyl coa–> citrate)

isocitrate dehydrogenase (isocitrate –> alpha KG)

alpha-KG dehydrogenase (alpha KG –> succinyl-coa)

Question 8

citrate synthase

Answer 8

oxaloacetate + acetyl coa –> citrate

condensation from a 2C (acetyl coa) and 4C (ox.) to generate a 6C

the thirster bind in acetyl coa is used to synthesize citrate

there is a negative free energy, thus making is irreversible

Question 9

aconitase

Answer 9

citrate to isocitrate

reversible isomérisation

Question 10

isocitrate dehydrogenase

Answer 10

isocitrate + NAD+ –> alpha KG + CO2 + NADH + H+

dehydrogenase reaction generates NADH and decarboxylation releases a carbon via CO2

CO2 is derived from oxaloacetate

Question 11

alpha KG dehydrogenase

Answer 11

alpha KG + CoA + NAD+ –> succinylcholine CoA + CO2 + NADH + H+

oxidative decarboxyaltion genres NADH and CO2, this provides the energy to generate the high energy intermediate: SUCCINYL COA

multi enzyme complex

Question 12

succinyl coa synthase

Answer 12

succinyl coa + GDP + Pi –> succinate + GTP

uses energy of succcinyl coa to generate gtp

Question 13

succinate dehydrogenase

Answer 13

succiante E-FAD –> E-FADH2 + fumarate

covalently bound to FAD

the succinate DH-FAD is oxidized to form succinate DH- FADH2. FAD is then rested by funnelling its e- into the ETC

Question 14

where is FADH2 donated

Answer 14

the e- from FADH2 from succinate DH is donated to complex II to the ETC

Question 15

fumarase

Answer 15

fumarate + H2O –> malate

Question 16

malate dehydrogenase

Answer 16

malate + NAD= –> oxaloacetate + NADH + H+

final step of CAC

although its endergonic, the true delta G is 0 because :
- in vivo [malate]»> [oxalo]

the next reaction involving citrate synthase is highly exergonic, which allows the formation of citrate to be exergonic even at low [oxalo] (due to acetyl coats energy supplies by the thirster bond)

this implies that there is a coupling of both reactions to help CAC move forward

Question 17

CAC balance sheet

Answer 17

3 NADH x 2.5 = 7.5 ATP

FADH2 x 1.5 = 1.5 ATP

GTP =ATP

total of 10 ATP

total of CAC, glycolysis and PDC = (10x2 bc 2 acetyl coa/glu) + 7 + (2.5 x 2 pyruvate/glu) = 32 ATP/glucose

Question 18

regulation of citrate synthase

Answer 18

substrate availability of acetyl coa and oxaloacetate

in vivo acetyl coa and oxaloacetate do not saturate citrate synthase

the amount of acetyl coa is derived by PDC reaction

product inhibition via citrate the product of the reaction acts as a competitive inhibitor of oxaloacetate binding to the citrate synthase

competitive feedback, succinyl coa competes with acetyl coa to inhibit

allosteric inhibition via NADH (noty a product)

allosteric activation (ADP)

Question 19

regulation of isocitrate dehydrogenase

Answer 19

product inhibition via NADH

allosteric activation via ADP and Ca2+

when isocitrate DH is inhibited,, the amount of isocitrate will build and since the aconite reaction is reversible, citrate will be regenerated and released in the cytoplasm

citrate in the cytoplasm activates acetyl coa carboxylase , thus activating FA synthesis and this inhibits PFK thus inhibiting glycolysis

Question 20

surplus of citrate indicates

Answer 20

high energy

Question 21

regulation of alpha keto glutarate DH

Answer 21

product inhibition via NADH and succinyl coa

allosteric activation via Ca2+

Question 22

what does citrate also inhibit

Answer 22

PFK1 allosterically, which inhibits the conversion of F6P –> F1,6BP

the committing step to glucose metabolism

Question 23

PDC is switched off when

Answer 23

energy charge is high, product inhibition via acetyl coa and NADH.

this activates PDH kinase

Question 24

regulation of pyruvate carboxylase

Answer 24

one molecule of oxaloacetate required to run CAC

accumulation of acetyl via indicates that there e is a need for oxaloacetate in order to run CAC

Question 25

excess pyruvate is converted into

Answer 25

oxaloacetate when carrboxylated

Question 26

name the anabolic/catabolic processes of pyruvate

Answer 26

catabolic= synthesis of acetyl coa

anabolic = synthesis of oxaloacetate