Question

If a patient experiences a mitochondrial PEP carboxy kinase deficiency, which therapy could best allow gluconeogenesis to continue? Please explain why

a.Lactate supplementation

b.Amino acid supplementation

c.Malate supplementation

d.Fattyacidsupplementation

Answer 1

d. Fatty acids supplementation

The glycerol part of fat is phosphorylated by glycerol kinase in the liver cytosol by ATP to glycerol-3-phosphate. It is then oxidized to dihydroxyacetone phosphate (DHAP) by an NAD+ dependent glycerol-3-phosphate dehydrogenase. This DHAP is converted to glyceraldehyde-3-phosphate and enters the gluconeogenic pathway.

Lactate get converted to pyruvate and then to oxaloacetate. Due to PEP carboxykinase deficiency, oxaloacetate is not converted to PEP.

Aminoacids that are transaminated to corresponding carbon skeletons enter the TCA cycle and get converted to oxaloacetate, but due to PEP caroxykinase deficiency does not get converted to PEP.

Malate get converted to oxaloacetate in TCA cycle, but due to PEP carboxykinase deficiency does not get converted to PEP.