Krebs Cycle and Oxidative Decarboxylation

Oxidative Decarboxylation of Pyruvic Acid

• Occurs in the mitochondria and is irreversible.
• Catalyzed by a complex of 3 enzymes and requires 5 coenzymes: TPP, lipoic acid, COASH, FAD, and NAD+.

Krebs Cycle

• Final common pathway for the complete oxidation of acetyl-CoA.
• Acetyl-CoA can be produced from the partial oxidation of carbohydrates, lipids, and protein.
• Located in the mitochondria of every cell.

Regulation of Krebs Cycle

• Rate is determined by cellular ATP demand.
• Low ATP and high ADP/AMP and NAD+ signal increased Krebs cycle activity leading to higher ATP production.
• High ATP and NADH signal inhibition of the Krebs cycle reducing ATP production.

Importance of Krebs Cycle

• Major source of energy, oxidizing acetyl-CoA produces 12 ATP.
• Provides succinyl-CoA (active succinate) for:
  • Hemoglobin synthesis
  • Ketolysis
  • Detoxification
• Supplies the body with precursors to amino acids:
  • Alanine from pyruvic acid.
  • Glutamic acid from α-ketoglutaric acid.
  • Aspartic acid from oxaloacetic acid.

Energy from Glucose Oxidation

• In the absence of oxygen, only anaerobic glycolysis occurs, generating 2 ATP.
• When oxygen is present, a complete oxidation of glucose generates 38 ATP:
  • Glycolysis: 2 ATP + 2 NADH + 2 Pyruvate = 8 ATP
  • 2 Pyruvate → 2 Acetyl-CoA + 2 NADH = 6 ATP
  • 2 Acetyl-CoA: 6 NADH + 2 FADH + 2 ATP = 24 ATP

Hexose Monophosphate Shunt (HMP Shunt)

• Alternative pathway for glucose oxidation that generates pentoses as intermediates.
• Occurs in the cytosol of cells requiring NADPH:
  • Liver, adipose tissue, lactating mammary gland (fatty acid synthesis).
  • Adrenal cortex, gonads, placenta (steroid synthesis).
  • Red blood cells (maintains ferrous iron in hemoglobin and membrane resistance to hemolysis).
  • Retina, cornea, lens (reduction of retinal to retinol).

Functions of HMP Shunt

• Produces NADPH + H+ (reduced coenzyme II) used for:
  • Synthesis of fatty acids.
  • Synthesis of cholesterol.
  • Synthesis of certain steroid hormones.
• Produces pentoses-5-phosphate (ribulose, xylulose, and ribose 5-P) necessary for:
  • Formation of nucleosides (base-pentose).
  • Formation of nucleotides (base-pentose-phosphate).
  • Formation of nucleic acids and nucleoproteins.

Uronic Acid Pathway

• Occurs in the cytosol.