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Beta Oxidation Pathway

  • Step 1: Oxidation by FAD forms double bond between α and β carbons of fatty acyl CoA.

  • Step 2: Hydration of the alkene forms an alcohol at beta carbon.

  • Step 3: Oxidation of alcohol by NAD+ converts to β-Ketoacyl-CoA (producing NADH).

  • Step 4: Thiolysis cleaves bond between α and β carbons, yielding Acetyl-CoA.

  • Each round produces Acetyl-CoA and shortens the fatty acid chain by two carbons.

  • Complete oxidation of palmitic acid (C16) produces 8 Acetyl-CoA, requires 7 cycles of beta oxidation, yielding 7 NADH and 7 FADH2.

Stoichiometry

  • Total reaction:
    Palmitoyl CoA+7CoASH+7FAD+7NAD++7H<em>2O→8Acetyl CoA+7FADH</em>2+7(NADH + H+)\text{Palmitoyl CoA} + 7 \text{CoASH} + 7 \text{FAD} + 7 \text{NAD}^+ + 7 \text{H}<em>2\text{O} \rightarrow 8 \text{Acetyl CoA} + 7 \text{FADH}</em>2 + 7 \text{(NADH + H}^+)

  • Complete beta oxidation of a 20-carbon fatty acid yields either:
    A. 8 Acetyl CoA, 7 FADH2, 7 NADH
    B. 10 Acetyl CoA, 9 FADH2, 9 NADH
    C. 9 Acetyl CoA, 10 FADH2, 10 NADH
    D. 20 Acetyl CoA, 20 FADH2, 20 NADH

Glycolysis Overview

  • Glycolysis consists of 10 steps, occurring in the cytosol.

  • First five reactions (Preparatory Phase): ATP is used to phosphorylate and activate glucose.

  • Next five reactions (Payoff Phase): net ATP generation occurs.

Phosphorylation of Glucose

  • Hexokinase has 4 isozymes; Hexokinase IV (glucokinase) differs in KM for glucose.

  • Phosphohexose isomerase converts Glucose 6-phosphate to Fructose 6-phosphate.

  • Two triose molecules (G3P) are used for every glucose molecule.

Payoff Phase of Glycolysis

  • Glyceraldehyde 3-phosphate dehydrogenase catalyzes oxidation and phosphorylation, generating NADH.

  • Substrate level phosphorylation produces 2 ATP from 1,3-Bisphosphoglycerate.

  • Hydration and conversion of 2-phosphoglycerate to phosphoenolpyruvate (PEP) precedes second substrate-level phosphorylation.

    • PEP to Pyruvate reaction strongly favored by tautomerization.

Inhibitor Impact

  • In the presence of HKB99 (a phosphoglycerate mutase inhibitor), potential accumulations include glucose-6-phosphate, phosphoenolpyruvate, 3-phosphoglycerate, 2-phosphoglycerate, or Glyceraldehyde 3-phosphate.