1-5 Tricarboxylic Acid Cycle

Question 1

Tricarboxylic Acid cycle overview

Answer 1

Accoutns for 2/3 of ATP produciton from fuel oxidation

Utilizes acetyl coA from glucose, FA, AA, acetate, ketone bodies

Occurs in mito matrix

Activity tighty coordinated with rate of ETC and oxidative phosphrylation by feedback regulation

Question 2

Soures of acetyl coA

Answer 2

palmitate, acetoacetate, glucose, pyruvate, ethanol, alanine

Question 3

Pyruvate to Acetyl CoA

Answer 3

In mitochondria

Pyruvate oxidized to acetyl coA by enzyme: pyruvate dehydrogenase complex (composed of thiaminePP, lipoate, FAD)

NAD+ CoASH + pyruvate ->NADH + H+ +Acetyl-CoA

Creates high energy thioester bond

Question 4

Regulation of pyruvate dehydrogenase complex

Answer 4

PDC phosphorylated by a kinase to INACTIVE form
Direct negative regulators of this kinase: Acetyl CoA, NADH
Indirect positive regulators of this kinase: pyruvate, ADP

Phosphatase removes PDC-p to active form PDC
Positive regulator of phosphatase: Ca+2 (because muscles cells produce much Ca when working therefore they need more ATP produced)

Question 5

Largest free energy changes in TCA

Answer 5

Isocitrate +NAD+ -> a-Ketoglutarate + NADH + H+ +CO2

a-Ketoglutarate + NAD+ -> Succinyl CoA + NADH + H+ + CO2

Question 6

Key regulator of TCA cycle

Answer 6

Isocitrate dehydrogenase: catalyzes
isocitrate + NAD+ -> a-ketoglutarate + NADH + H+ + CO2

Enzyme + regulated by: ADP(allosteric, shifts curve from sigmoidal up to hyperbolic), Ca+2

Enzyme - regulated by: NADH

Question 7

Three main regulators of TCA cycle

Answer 7

1. Isocitrate dehydrogenase: isocitrate->a-ketogularate
2. a-ketoglutarate dehydrogenase: a-ketoglutarate -> succinyl CoA
3. malate dehydrogenase: malate->oxaloacetate

Question 8

Energy yield from TCA cycle

Answer 8

Per mole of Acetyl CoA:
3 NADH = 7.5 ATP
1 FAD(2H) = 1.5 ATP
1 GTP

Question 9

Intermediates of TCA used for biosynthesis

Answer 9

Acteyl CoA
Citrate- FA synth
Isocitrate
a-ketoglutarate-AA synth
Succinyl CoA- Heme synth
Malate- gluconeogenesis
Oxaloacetate- AA synth

Question 10

Anaplerotic rxns to replenish carbon skeletons of TCA

Answer 10

AA->pyruvate

pyruvate + CO2(biotin carrier) + Acetyl CoA + ATP via pyruvate carboxylase ->oxaloacetate + ADP +Pi

Valine, isoleucine, odd chain FA->propionyl CoA

propionyl CoA via pyriodozyl phosphate -> succinyl coA

AA->glutamate

Glutamate vis transaminase(TA)-> a-ketoglutarate

Question 11

Glutaminolysis

Answer 11

glutamine is lysed to glutamate, aspartate, CO2, pyruvate, lactate, alanine and citrate

Active in most proliferation and especially tumor cells, ROS species produced which inhibit TCA step of citrate to isocitrate, glutamine enters the cell and remaining TCA enzymes produce (above)

glutamine most abundant AA in plasma

glutamate and FA are immunosupressive and help tumor live