Fate of PyruvateFate of Pyruvate& Citric Acid Cycle& Citric Acid Cycle

Introduction of Glucose Metabolism Introduction of Glucose Metabolism Lecture-3Lecture-3

Fate of pyruvateFate of pyruvate

1- LactateLactate (in cytosol)(in cytosol) Enzyme: lactate dehyrogenase (LDH)Enzyme: lactate dehyrogenase (LDH) in anaerobic glycolysis

2- Acetyl CoAAcetyl CoA in mitochondriain mitochondria Enzyme: Enzyme: pyruvate dehydrogenasepyruvate dehydrogenase occurs in aerobic glycolysis Acetyl CoA is required for citric acid cycle (CAC)

3- OxalacetateOxalacetate in mitochondriain mitochondria EnzymeEnzyme: : pyruvate carboxylase pyruvate carboxylase Oxalacetate is required for: 1- Citric acid cycle (condenses with acetyl CoA): to yield energy ATP OR 2-Gluconeogenesis (to synthesize glucose)

LACTATELACTATE

Oxygen&

Mitochondria

No OxygenNo Mitochondria

OR BOTH

GlucoseGlucose

PYRUVATEPYRUVATE

ACETYL CoAACETYL CoA

CITRIC ACID CYCLECITRIC ACID CYCLE

OXALACETATEOXALACETATE

Fate ofFate of PyruvatePyruvate

glycolysisGluconeogenesis

mitochondria

LACTATE DEHYDROGENASELACTATE DEHYDROGENASE

FATES OF PYRUVATEFATES OF PYRUVATE

OXIDATIVE DECARBOXYLATION OF PYRUVATEOXIDATIVE DECARBOXYLATION OF PYRUVATE

Allosteric Regulation

Formation of acetyl CoA from pyruvateFormation of acetyl CoA from pyruvate

• Pyruvate (end product of aerobic glycolysis) is transported into the mitochondria.

• In the mitochondrial matrixmitochondrial matrix, pyruvate is converted to acetyl CoA acetyl CoA by pyruvate dehydrogenase complex pyruvate dehydrogenase complex (multienzyme complex) This reaction is irreversible

• Pyruvate dehydrogenase complex Pyruvate dehydrogenase complex is composed of three enzymes & five coenzymes

• Coenzymes of the complex Coenzymes of the complex are derived from water soluble vitamins:

1- Thiamine pyruphosphate, TPP Thiamine pyruphosphate, TPP (derived from thiamine, vitamin B1) 2- NAD+NAD+ (derived from niacin) 3- FAD FAD (derived from riboflavin) 4- Lipoic acidLipoic acid 5- Coenzyme ACoenzyme A (derived from pantothenic acid)

Pyruvate dehydrogenase Pyruvate dehydrogenase complexcomplex

PYRUVATEPYRUVATEACETYL CoAACETYL CoA

Citric acid cycle Citric acid cycle or,(Krebs cycle)(Krebs cycle)

Citric Acid CycleCitric Acid Cycle

Citric acid cycleCitric acid cycle is the final pathway where the oxidative metabolism of

CarbohydratesCarbohydrates (as glucose), proteinsproteins (amino acids) & lipidslipids (fatty acids) to yield energy (ATPATP)

Acetyl CoA Acetyl CoA is the end product for oxidation of carbohydrates, lipids & proteinsAcetyl CoA Acetyl CoA condenses with oxalacetate oxalacetate to form citrate (first reaction of the cycle)

3 NADH are produced = 3 X 3 = 9 ATP (by oxidative phosphorylation)9 ATP (by oxidative phosphorylation)One FADH2 is produced = 1 X 2 = 2 ATP (by oxidative phosphorylation)2 ATP (by oxidative phosphorylation)

One ATP One ATP is produced (by substrate level phosphorylationby substrate level phosphorylation)Net = 12 ATP / one acetyl CoANet = 12 ATP / one acetyl CoA

Citric Acid Cycle CYCLE - SUMMARYCitric Acid Cycle CYCLE - SUMMARY

Acetyl CoA3 NAD

3 NADH + H

1 FAD

1 FADH2

1 ADP1 ATP

2 CO2

KREBS CYCLE REACTIONS (1)KREBS CYCLE REACTIONS (1)

KREBS CYCLE REACTIONS (2)KREBS CYCLE REACTIONS (2)

Succinate Succinate ThiokinaseThiokinase

Substrate-LevelPhosphorylation

KREBS CYCLE REACTIONS (3)KREBS CYCLE REACTIONS (3)

KREBS CYCLE: ENERGY YIELDKREBS CYCLE: ENERGY YIELD

Citric acid cycle Citric acid cycle or,(Krebs cycle)(Krebs cycle)