Role of ATP II Flashcards
(11 cards)
Role of pyruvate in metabolism
- Lactate
- Oxaloacetate
- Acetyl-CoA
- Alanine
Transport of pyruvate into the mitochondrion
- In aerobic conditions, occurs via specific carrier proteins embedded in the mitochondrial membrane
- Pyruvate undergoes oxidative decarboxylation by the pyruvate dehydrogenase complex to from Acetyl CoA
- Pyruvate + CoA + NAD+ -> Acetyl CoA + CO2 + NADH + H+
- Reaction is irreversible and is the link between glycolysis and citric acid cycle
Pyruvate dehydrogenase complex
• 3 different enzymes & 5 different coenzymes
◦ Thiamine pyrophosphate (TPP), NAD+, CoA, Flavine adenine dinucleotide (FAD) and lipoic acid
• 4 different vitamins are vital to this complex in humans
◦ Thiamine (TPP), Riboflavin (FAD), Niacin (NAD) and Pantothenate (CoA)
Tricarboxylic acid (TCA) cycle
- Also known as citric acid or krebs cycle
- Final common pathway for the oxidation of fuel molecules
- In 8 steps, acetyl residues (CH3-CO-) are oxidised to CO2
- Reducing equivalents transferred to NAD+ or ubiquinone and from there to the respiratory chain
Nine enzymatic steps in the cycle
- Condensation - Citrate synthase
- Dehydration - Aconitase
- Hydration - Aconitase
- Oxidative decarboxylation - Isocitrate dehydrogenase
- Oxidative decarboxylation - Alpha-Ketoglutarate dehydrogenase
- Substrate-level phosphorylation - Succinyl-CoA-Synthase
- Dehydrogenation - Succinate dehydrogenase
- Hydration - Fumarase
- Dehydrogenation - Malate dehydrogenase
Regulation of the TCA cycle
Flow of carbon atoms from pyruvate into and through the TCA cycle is tightly regulated at 2 levels:
• Conversion of pyruvate to acetyl-CoA (PDH reaction)
• Entry of acetyl-CoA into the TCA cycle (Citrate synthase reaction)
Also regulated at isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase reactions
Fatty acids and amino acids can be sources of Acetyl-CoA
Products of TCA Cycle
Energy released from oxidation is conserved in the reduction of 3 NADH, 1 FADH2, 1 GTP (ATP)
2 CO2 also produced
Products of glycolysis and TCA cycle
Glycolysis: Pyruvate and NADH
TCA cycle: 3 NADH, 1 FADH2, 1 GTP (ATP)
BUT:
• The inner mitochondrial membrane is impermeable to NADH
• There is no carrier in the membrane to transport it across
Shuttles
NADH is not transported but its 2 electrons enter by shuttles
There are 2 shuttles:
• The gylcerol-3-phosphate shuttle, especially prevalent in brain and muscle
• The malate-aspartate shuttle, in liver and heart
Both shuttles act to regenerate NAD+ and make 1.5 or 2.5 moles of ATP
Electron transport chain
• Comprises 4 large multi-unit proteins intrinsic to the inner mitochondrial membrane
• Catalyse a seroes of reactions:
◦ NADH + H+ + 1/2 O2 = NAD+ + H2O
• Energy released from this reaction not released as heat but tightly coupled to production of ATP
Electron transport chain - 4 complexes
- Linked by 2 soluble proteins
- Ubiquinone (coenzyme Q) - lipid soluble benzoquinone with a long isoprenoid tail
- Cytochrome C - free to move in membrane by diffusion (not part of complexes)
