Lec 18/19 Harvesting electrons

pyruvate dehydrogenase complex,

oxidatively

decarboxylates pyruvate to form acetyl CoA

pyruvate dehydrogenase complex location

mitochondrial matrix enzyme

why convert pyruvate to acetyl CoA

to enter into the TCA cycle

During which conditions would pyruvate be converted to acetyl coA

Under aerobic conditions, where oxygen is available for cellular respiration.

Largest Multi-enzyme complex known (much bigger than ribosomes)

Pyruvate Dehydrogenase Complex

Activated Carriers

NADH/NADPH
FADH2FMNH2
Coenzyme A
Lipoamide
Thiamine pyrophosphate
Biotin

PDH uses which activated carriers

NADH
FADH2
COenzyme A
Lipoamide
Thiamine pyrophosphate

Thiamine deficiency

results in insufficient pyruvate dehydrogenase activity

Thiamine

essential

cofactor for a number of

enzymes including pyruvate

dehydrogenase

Arsenite and mercury can

poison PDH by covalent binding to the sulfhydryls on lipoamide

Pyruvate Dehydrogenase is regulated by

both product inhibition and phosphorylation

PDH product inhibition regulation

high levels of products: NADH, Acetyl-CoA and ATP
Indicating HIGH ENERGY CONDI TIONS

PDH phosphorylation regulation

PDH-kinase phosphorylates PDH to inactivate

How is phosphorylation inactivation of PDH reversed

by dephosphorylation mediated by PDH-phosphatase.

What is an example of a condition where PDH-kinase would want to inactivate PDH

hypoxia

The formation of acetyl CoA from pyruvate is

considered

irreversible

Why is formation of acetyl CoA from pyruvate irreversible in humans

we cant make glucose from lipids to back track

glyoxylate cycle

fund in some organisms to turn lipids back into glucose (HUMANS CANT)

two key functions of the citric acid cycle are:

• To harvest high-energy electrons from carbon

fuels in the form of NADH and FADH2.

• To provide carbon skeletons for the

biosynthesis of other molecules

Acetyl CoA enters the citric acid cycle

where

electrons are harvested for oxidative

phosphorylation

first stage of the citric acid

cycle

two carbons are introduced

into the cycle by combining an

acetyl group with a four-carbon

compound, oxaloacetate.

What happens after 2 carbons are combined with 4-C oxaloacetate

is the formation of citrate (6 carbon)

What happens after citrate is formed

undergoes two oxidative

decarboxylations, generating two

molecules of CO2

Second stage of citric acid cycle

oxaloacetate

Citrate Synthase

catalyzes reaction of oxaloacetate (4C) with acetyl CoA

(2C) to make citrate (6C)

Significance of citrate synthase

Only step in TCA cycle that involves the formation of a C-C bond

Aconitase

turns Citrate into Isocitrate

Isocitrate Dehydrogenase

oxidative decarboxylation of isocitrate to alpha-ketoglutarate forming 1st CO2 and NADH

alpha -Ketoglutarate Dehydrogenase

catalyzes the conversion of alpha-ketoglutarate to succinyl-CoA, releasing the second CO2 and producing NADH.

Succinyl-CoA Synthetase

catalyzes the conversion of succinyl-CoA to succinate, generating GTP
SUBSTRATE LEVEL PHOSPHORYLATION

Succinyl-CoA Synthetase utilizes a

phospho-His intermediate to transfer a P

Succinate Dehydrogenase

is an enzyme that catalyzes the oxidation of succinate to fumarate while reducing FAD to FADH2 in mitochondrial inner membrane

Succinate dehydrogenase

participates in both

TCA cycle AND in the

mitochondrial electron

transport chain

Malate

Dehydrogenase

is an enzyme that catalyzes the conversion of malate to oxaloacetate, while reducing NAD+ to NADH

Within TCA, when does substrate level phosphorylation occur

by succinyl CoA synthetase

Within TCA, when does direct transfer of electrons occur

through succinate dehydrogenase

ATP yield from complete oxidation of glucose

30-32

The TCA cycle is a source of

biosynthetic precursors like aspartate and glutamate

But, if citric acid cycle components are utilized for

biosynthesis,

intermediates must be replaced through anaplerotic reactions

A prominent anaplerotic

reaction

is catalyzed by

pyruvate carboxylase.