Metabolic limitation – Why can animals not convert even-chain fatty acids into net glucose via standard central metabolic pathways?

Introduction / Context:
Textbook biochemistry emphasizes that animals cannot generate net glucose from even-chain fatty acids. The biochemical reason rests on carbon accounting and reaction irreversibility. This question asks you to identify the key metabolic block that prevents acetyl-CoA carbons from reappearing as glucose in animals.

Given Data / Assumptions:

• Even-chain fatty acids degrade by beta-oxidation to acetyl-CoA units.
• Pyruvate dehydrogenase converts pyruvate to acetyl-CoA irreversibly.
• Animals do not have the glyoxylate cycle (isocitrate lyase and malate synthase), which would bypass CO2-releasing steps.

Concept / Approach:
In the tricarboxylic acid cycle, acetyl-CoA carbons enter and equivalent carbons leave as CO2 over turns of the cycle, yielding no net gain of oxaloacetate for gluconeogenesis. Because pyruvate dehydrogenase is irreversible, acetyl-CoA cannot be converted upstream to pyruvate or oxaloacetate. Plants, fungi, and bacteria use the glyoxylate cycle to conserve carbons for gluconeogenesis, but animals lack this shunt.

Step-by-Step Solution:

Verification / Alternative check:
Tracer studies show acetyl-CoA carbons do not accumulate in gluconeogenic intermediates in animals; odd-chain fatty acids can contribute via propionyl-CoA → succinyl-CoA → oxaloacetate, highlighting the exception that proves the rule.

Why Other Options Are Wrong:

• Lack of pyruvate carboxylase: false; this enzyme is present and essential for gluconeogenesis.
• Beta-oxidation produces acetyl-CoA, not lactate.
• Glycolysis is active in liver; the issue is directionality and carbon balance, not pathway absence.
• Malate–aspartate shuttle exists in animals; it transfers reducing equivalents.

Common Pitfalls:
Forgetting about the glyoxylate cycle in microbes/plants and assuming acetyl-CoA can be “pulled back” to pyruvate; the PDH step blocks this.

Final Answer:
Acetyl-CoA cannot be converted back to pyruvate in animals (pyruvate dehydrogenase step is irreversible)