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Two very hyperketotic children

acacBHObIn a series of experiments using isolated rat cardiomyocytes (heart muscle cells), the consumption of oxygen was measured when various substrates were added. The figures below show the consumption of oxygen when the cells were provided with 10 µmol /L acetoacetate or beta-hydroxybutyrate as substrates (mean ± sd for 5 x replicate incubations).

substrate
nmol oxygen consumed /min /mg protein
acetoacetate
240 ± 4
beta-hydroxybutyrate
270 ± 3

 

What conclusions can you draw from these results?

bHBdHIf more oxygen is consumed in the metabolism of beta-hydroxybutyrate than of acetoacetate, this suggests that it is likely that the first step in metabolism of beta-hydroxybutyrate involves its oxidation, presumably to acetoacetate, the reverse of the reaction in the liver, in which acetoacetate is reduced to beta-hydroxybutyrate:

We have already seen (in the exercise on Two boys with profound fasting hypoglycaemia and no ketone bodies) that the advantage of reducing acetoacetate to beta-hydroxybutyrate in the liver is that acetoacetate is unstable, and undergoes non-enzymic decarboxylation to acetone, which is metabolically more or less useless. Reduction to beta-hydroxybutyrate thus prevents loss of metabolic fuel in fasting and starvation.

What do you think is the advantage to extra-hepatic tissues of receiving beta-hydroxybutyrate rather than acetoacetate?

See the answer