Carnitine shuttles long chain fatty acids into mitochondria for beta oxidation
Expansion
- Fatty acids are activated to acyl-CoA in the cytoplasm
- Long chain acyl-CoA requires the carnitine shuttle (CPT1 and CPT2) to enter the mitochondrion. Medium and short chain fatty acids diffuse in freely
- Beta oxidation removes two carbons per cycle, yielding acetyl-CoA, NADH and FADH2
- Acetyl-CoA enters the Krebs cycle, or in fasting is converted to ketone bodies
Fat yields far more energy per gram than carbohydrate (about 9 versus 4 kcal), but requires oxygen throughout and cannot support anaerobic work.
CPT1 is inhibited by malonyl-CoA, the first committed intermediate of fatty acid synthesis, which elegantly prevents simultaneous synthesis and breakdown.
Inborn errors illustrate the pathway. Medium chain acyl-CoA dehydrogenase deficiency (MCADD), the commonest, presents in infancy with hypoketotic hypoglycaemia, vomiting and encephalopathy during fasting or intercurrent illness. The paradox of hypoglycaemia without ketones is the diagnostic clue, since fat cannot be used to make ketones and glucose is therefore consumed rapidly. It is screened for on the newborn blood spot.