Carbohydrate Metabolism

⚡ The Complete Respiration Masterclass

Every Step, Every Enzyme: Glycolysis to TCA Cycle

1. Glycolysis (EMP Pathway): All 10 Steps

Glycolysis occurs in the cytosol and is universally conserved. It consists of a Preparatory (Investment) Phase (Steps 1-5) and a Payoff Phase (Steps 6-10).

🔥 High-Yield Facts & Inhibitors:

• Irreversible Steps: 1, 3, and 10. These are the regulatory checkpoints.
• Iodoacetate / Heavy Metals: Strictly inhibits GAPDH (Step 6) by binding to its active site sulfhydryl (-SH) group.
• Fluoride: A potent competitive inhibitor of Enolase (Step 9). Fluoride is added to blood collection tubes to prevent RBCs from metabolizing glucose before lab testing.

2. Metabolic Shifts

Pasteur Effect: The sharp decrease in glucose consumption when oxygen is introduced. Oxygen allows the TCA cycle and ETC to run, producing 32 ATP per glucose, so the cell slows down glycolysis (by inhibiting PFK-1 via high ATP/Citrate).

Warburg Effect (Cancer): Cancer cells bypass the Pasteur effect. They aggressively perform glycolysis and convert pyruvate to lactate even in the presence of abundant oxygen (Aerobic Glycolysis). This provides rapid building blocks for tumor growth.

3. Link Reaction (PDH Complex)

Pyruvate enters the mitochondrial matrix and is converted to Acetyl-CoA by the Pyruvate Dehydrogenase (PDH) Mega-complex.

Pyruvate + CoA + NAD⁺ → Acetyl-CoA + CO₂ + NADH

• E1: Pyruvate Dehydrogenase (requires TPP)
• E2: Transacetylase (requires Lipoic Acid, CoA)
• E3: Dehydrogenase (requires FAD, NAD⁺)

4. The TCA Cycle (Krebs Cycle): All 8 Steps

Occurs in the mitochondrial matrix. It is the final oxidative pathway for carbohydrates, fats, and proteins.

🔥 Critical Exam Facts:

• Succinate Dehydrogenase (Step 6): The ONLY TCA enzyme embedded in the inner mitochondrial membrane. It also acts as Complex II of the Electron Transport Chain.
• Substrate-Level Phosphorylation: Occurs only at Step 5 (Succinyl-CoA Synthetase), generating 1 GTP (which converts to ATP).
• Mnemonic for Substrates: "Citrate Is Krebs' Starting Substrate For Making Oxaloacetate." (Citrate, Isocitrate, α-KG, Succinyl-CoA, Succinate, Fumarate, Malate, Oxaloacetate).