04: TCA Cycle and PDH Complex Overview

Glycolysis occurs in the _____

cytoplasm

Citric acid cycle occurs in the _____

mitochondrial matrix

Oxidative phosphorylation occurs in the_______ of the mitochondria.

inner membrane

succinate dehydrogenase is located in the _____ of the mitochondria

inner membrane

Conversion of Pyruvate to Acetyl-CoA

• Overall Reaction

  • oxidative decarboxylation of pyruvate to form acetyl CoA

  • first carbons of glucose to be fully oxidized

acetyl CoA

Conversion of Pyruvate to Acetyl-CoA

• Catalyzed by the _____

pyruvate dehydrogenase complex

Conversion of Pyruvate to Acetyl-CoA requires 5 coenzymes

• prosthetic groups

TPP, lipoyl-lysine, and FAD

Conversion of Pyruvate to Acetyl-CoA requires 5 coenzymes

• co-substrates

NAD+ and CoA-SH

The function of CoA:

accept and carry acetyl groups

The lipoic acid is covalently linked to the enzyme via a ____ residue

lysine (lys,K)

Pyruvate dehydrogenase (PDH) complex

• E1

pyruvate dehydrogenase

Pyruvate dehydrogenase (PDH) complex

• E2

dihydrolipoyl transacetylase

Pyruvate dehydrogenase (PDH) complex

• E3

dihydrolipoyl dehydrogenase

two regulatory enzymes of PDH complex

Pyruvate dehydrogenase kinase, Pyruvate dehydrogenase phosphatase

PDH E1 COfactor

Thiamine Pyrophosphate (TPP)

PDH E2 COfactor

Lipoic acid and Coenzyme A (CoA)

PDH E3 COfactor

FAD and NAD+

Regulatory enzymes alternately activate and inactivate E1

• PDH kinase phosphorylates E1 and makes it _____

• PDH phosphatase dephosphorylates E1 and makes it ______

inactive, active

High levels of Pyruvate _____ the PDH complex

activate

High levels of ATP, Acetyl CoA, and NADH ______ the PDH complex

inhibit

From ONE molecule of pyruvate, in the TCA cycle: ________ are produced

3 NADH, 1 FADH2, and 1 GTP

NADH = ____ ATP

3

FADH2 =_____ATP

2

Citrate synthase is also inhibited by ____



α-Ketoglutarate is an important branch point for amino acid metabolism.



Succinyl-CoA communicates flow at this branch point to the start of the cycle.

succinyl-CoA.citrate

Regulation of -_____controls citrate levels.



Aconitase is reversible.



Inhibition of IDH leads to accumulation of isocitrate and reverses acconitase.



Accumulated citrate leaves mitochondria and inhibits phosphofructokinase (PFK-1) in glycolysis.

isocitrate dehydrogenase (IDH)