Chapter 19 Flashcards
(18 cards)
Overview of the Citric Acid Cycle
- Receives and delivers compounds
- Key role in oxidation of fuels
- convert fuels into acetyl-CoA
- acetyl-CoA for cycle entry
- oxidation reactions in the cycle generate high
energy electrons, which are captured as FADH2 and NADH - used to make ATP in oxidative
phosphorylation - 1 ATP also generated in citric acid cycle
Citric Acid Cycle - First Stage of Cellular Respiration
- Receives Acetyl-CoA from glucose, fatty acid or amino acid metabolism
- Generates high energy electrons for oxidative phosphorylation
- Occurs in the mitochondria
Citric Acid Cycle: 2-parts
- Oxidize carbon atoms to CO2
- Regenerate oxaloacetate
- Oxidize carbon atoms to CO2
- Involves joining 2-C acetyl to 4-C oxaloacetate to form 6-C citrate
- Followed by oxidative decarboxylation
- Back to 4-C compound
- 2 CO2, 2 NADH produced
- Regenerate oxaloacetate
- Rearrangement of 4-C compounds
- Harvest energy as ATP, NADH, and FADH2
Stage 1: Citrate Synthase
- catalyzes the condensation of acetyl-CoA and oxaloacetate to form citrate.
- Relies on thioester hydrolysis to drive the reaction
- Thioester hydrolysis is specific to Citryl-CoA through “induced fit” into the enzyme active site
- Acetyl-CoA active site not generated until oxaloacetate binds
Stage 1: Citrate Isomerization
- Aconitase catalyzes the formation of isocitrate from citrate
- Acontinase moves the hydroxyl from central carbon closer to terminal carbon by dehydration and hydration reactions
Stage 1: Oxidative Decarboxylation
- Isocitrate dehydrogenase converts isocitrate into alpha-ketoglutarate
- oxidative decarboxylation reaction
- electrons (proton) captured by NAD+ to form NADH
- Oxalosuccinate is unstable: central caboxyl group leaves as CO2
Stage 1: Succinyl CoA formed from α-ketoglutarate
α-ketoglutarate dehydrogenase (KD) complex
- Homologous to PDH complex (pyruvate dehydrogenase complex))
- PDH: pyruvate (3-C) + NAD+ → acetyl CoA (2-C) + CO2 + NADH
- α-KD: α-ketoglutarate (5-C) + NAD+ → succinyl CoA (4-C) + CO2 + NADH
- Oxidative decarboxylation
- electrons captured by NADH
- thioester formed with high energy transfer potential is formed
Stage 2: High Energy Transfer from Succinyl CoA
- Succinyl CoA synthetase catalyzes the cleavage of a thioester linkage (-33.5 kJ/mol)
- Energy is used in the phosphorylation of a purine dinucleotide:
- ADP to ATP (muscle)
- GDP to GTP (liver)
Stage 2: High Energy Transfer from Succinyl CoA (2)
Substrate-level phosphorylation
1. Succinyl phosphate is formed
2. Phosphate transferred from histidine (enzyme) to ADP (purine dinucleotide)
Stage 2: Oxidation of Succinate to Oxaloacetate
- Oxidation reaction catalysed by succinate dehydrogenase
- enzyme located on inner mitochondrial membrane
- FADH2 that is generated feeds directly in the electron transport chain - Hydration by fumarase
- Another Oxidation reaction catalysed by malate dehydrogenase
- Reaction is unfavourable (+29.7 kJ/mol) but driven by use of products
- Rapid use of NADH and oxaloacetate shifts the reaction equilibrium
The Citric Acid Cycle
- Carbons: 2-C in (acetyl CoA) and 2-C out (2 CO2)
- Hydrogens/electrons: 4 pairs: 3-NADH (each will generate 2.5 ATP), 1-FADH2 (each will generate 1.5 ATP)
- Water: 2 molecules
- 1-cycle:
3-NADH = 7.5-ATP
1 FADH2 = 1.5-ATP
+ 1-ATP = 10-ATP / turn of the citric acid cycle - aerobic conditions
Regulation of the Citric Acid Cycle (entry of Acetyl CoA)
- regulation of pyruvate dehydrogenase complex (PDH)
- regulation of fatty acid oxidation
Regulation of Citric Acid Cycle (Controls within cycle)
- Isocitrate dehydrogenase
- Activated by ADP
- Inhibited by NADH and ATP - α-ketoglutarate dehydrogenase (α-KD)
- Inhibited by NADH, ATP and succinyl CoA
Synthesis of Metabolic Precursors
- Compounds in citric acid cycle are used as precursors for biosynthesis
Replenishing the Citric Acid Cycle
- CAC intermediates must be replenished if they leave the
cycle to serve as biosynthetic precursors - Pyruvate carboxylase: Anaplerotic (“to fill up”) reaction
- Generates oxaloacetate to feed CAC intermediates
- Regulation: requires acetyl-CoA to activate
- Fate of oxaloacetate
- High energy state → gluconeogenesis
- Low energy state → replenish CAC
Glyoxylate Cycle
enables plants and bacteria to convert fats into carbohydrates
- isocitrate converted to: glyoxylate (2-C), succinate (4-C)
- malate synthase – combine acetyl CoA and glyoxylate to form malate
- result is 2 acetyl CoAs, used to make oxaloacetate (gluconeogenic)
