Chapter_19_biochem_q

Chapter 19: The Citric Acid Cycle

Learning Objectives

  • Differentiate anaerobic and aerobic metabolism via electron flow in catabolism.

  • Draw and label mitochondrial structure: outer and inner membrane, intermembrane space, matrix. Show entry of carbohydrates and lipids. Locate PDC and citric acid cycle.

  • Explain the amphibolic nature of the citric acid cycle.

  • Write net reactions for PDC and citric acid cycle.

  • Describe chemistry of each step in PDC and differentiate roles of coenzymes: thiamine pyrophosphate, CoASH, and lipoic acid.

  • For citric acid cycle:

    • Know metabolites, enzyme names, and their chemistry.

    • Recognize names with structures.

    • Identify reactions/enzymes that produce/consume GTP/GDP, NAD+/NADH, FAD/FADH2.

  • List regulatory enzymes (PDH, CS, ICDH, aKGDH) with their activators/inhibitors (ATP/ADP, NADH/NAD+ ratios).

  • Describe glyoxylate cycle’s importance and differentiate from the citric acid cycle: List two unique enzymes, recognize overall net reaction.

  • Discuss citric acid cycle's central role in catabolism of carbohydrates/lipids/proteins.

  • Explore citric acid cycle's role in anabolism: list intermediates used for biosynthesis.

  • Define anaplerotic reactions and list involved metabolites/enzyme.

  • Summarize aerobic metabolism energy production post-citric acid cycle (ATP).

PDC & Citric Acid Cycle Cheat Sheet

  • Presented on quizzes and exams for quick reference.

Central Role of the Citric Acid Cycle in Metabolism

  • Evolution of aerobic metabolism allows for increased energy extraction from nutrients.

  • Ultimate electron acceptor in catabolism: O2.

  • Pathways involved in anaerobic and aerobic metabolism identified.

The Overall Pathway of the Citric Acid Cycle

  • Aerobic metabolism occurs in the mitochondrial matrix.

  • Precursors for the citric acid cycle include Acetyl-CoA.

  • Carbon fate in Acetyl-CoA upon entering the citric acid cycle is outlined.

  • Electron acceptors and high-energy compounds produced by the cycle.

Key Features of the Citric Acid Cycle

  • Amphibolic role as it both builds and breaks down molecules (anabolic & catabolic).

  • Carbon sources for citric acid cycle noted (no biological examples of direct C–C bond cleavage in two-carbon compounds).

  • Chemical feasibility of cleaving two-carbon compounds to CO2 through the citric acid cycle.

Conversion of Pyruvate to Acetyl CoA

  • Pyruvate Dehydrogenase Complex (PDC)

    • Large multienzyme complex with three enzymes and five coenzymes.

    • Enzymes: Pyruvate decarboxylase, dihydrolipoyl transacetylase, dihydroxylipoxl dehydrogenase.

    • Regulatory Proteins: Pyruvate dehydrogenase kinase, pyruvate dehydrogenase phosphatase.

    • Overall net reaction for PDC will include loss of CO2, oxidation and formation of thioester.

Mechanism of the Pyruvate Dehydrogenase Complex

  • Stepwise conversion of pyruvate to acetyl-CoA includes:

    1. Decarboxylation (loss of CO2).

    2. Oxidation of keto group on C2.

    3. CoA activation via thioester bond formation.

    4. Lipoic acid oxidation and transfer of electrons to NAD+.

Coenzymes in the Pyruvate Dehydrogenase Complex

  • Coenzymes:

    • Thiamine Pyrophosphate (TPP)

    • Coenzyme A (CoA)

    • Lipoic Acid

Individual Reactions of the Citric Acid Cycle

  • Citric Acid Cycle (TCA Cycle, Krebs Cycle) breaks down two carbons from acetyl-CoA into CO2.

  • Location of citric acid cycle operation in cellular components.

  • Overall net reaction of the citric acid cycle written out.

Steps of the Citric Acid Cycle

  • Citric acid cycle steps characterized by:

    1. Citrate Synthase (CS) - C–C bond formation.

    2. Aconitase (AC) - Isomerization.

    3. Isocitrate Dehydrogenase (ICDH) - Oxidative decarboxylation.

    4. a-Ketoglutarate Dehydrogenase (aKGDH) - Oxidative decarboxylation.

    5. Succinyl-CoA Synthetase (SCoAS) - Substrate-level phosphorylation to make GTP.

    6. Succinate Dehydrogenase (SDH) - Oxidation.

    7. Fumarase (F) - Hydration.

    8. Malate Dehydrogenase (MDH) - Oxidation.

Summary of the Citric Acid Cycle

  • Enzymes that produce CO2: CDH, KGDH, PDC.

    • KGDH catalyzes a reaction similar to PDC.

  • Yield from citric acid cycle per acetyl-CoA:

    • NADH: 10 ATP (4NADH total).

    • FADH2: 1.5 ATP.

    • GTP production by SCoAS.

Energetics & Control of the Citric Acid Cycle

  • Regulatory control linked to the organism's metabolic state:

    • Resting state: High ATP/ADP, high NADH/NAD+.

    • Active state: Low ATP/ADP, low NADH/NAD+.

Regulation Sites of PDC & Citric Acid Cycle

  • Enzyme names involved in regulation indicated.

  • Product inhibition: Citrate (CS), PDC, KGDH.

  • Feedback inhibition: CS.

    • Importance of acetyl-CoA levels disabling PDC highlighted.

Glyoxylate Cycle: A Related Pathway

  • Glyoxylate cycle uses acetate for synthesizing four-carbon units and glucose in plants/bacteria.

  • Glyoxylate cycle bypasses some citric acid cycle reactions.

  • Identifies conditions when the glyoxylate cycle is utilized and specifies the organelle (glyoxysome).

Citric Acid Cycle in Catabolism

  • Citric acid cycle's central role in degrading polysaccharides, lipids, and proteins:

    • Path from starch/lipids to citric acid cycle traced.

    • Enzymes defined: Amylases (sugars), Proteases (proteins), Lipases (lipids).

    • Amino acid catabolism pathways noted for citric acid cycle entry.

Citric Acid Cycle in Anabolism

  • Key biosynthetic precursors sourced from citric acid cycle: glucose, amino acids, lipids, nitrogenous bases.

  • Metabolites directly used in anabolism specified (e.g. Oxaloacetate, α-KG).

Anaplerotic Reactions of the Citric Acid Cycle

  • Anaplerotic reactions replenish metabolites exhausted during anabolism.

  • Metabolites and enzymes in these reactions identified (Oxaloacetate via pyruvate).

  • Importance of pyruvate-to-oxaloacetate conversion for lipid degradation emphasized.

The Link to Oxygen

  • Citric acid cycle as a bridge linking nutrient energy to ATP:

    • Overall net reaction for aerobic catabolism of glucose outlined.

    • NADH/FADH2 as key biomolecules linking citric acid cycle with oxidative phosphorylation.

    • Effects of oxygen shortage on aerobic catabolism described.