Ketogenesis

Enzymes catalyze the formation of acetoninic substances, such as acetoacetate, β-hydroxybutyrate, and acetone, in the mitochondria of liver cells. Acetoacetyl-CoA serves as the initial compound for ketogenesis, with other acetoninic substances forming from this compound. The liver is the only organ where ketogenesis occurs in all animals except ruminants. In other tissues, such as the brain, acetoninic substances function as an energy source.

The level of acetoninic substances in the blood, not in the urine, indicates the difficulty of ketogenesis. β-hydroxybutyrate predominates during this process. The ratio of β-hydroxybutyrate to acetoacetate in the blood ranges from 1:1 to 10:1. During fasting or in type I diabetes, the levels of acetoninic substances increase in the blood (ketoemia) and urine (ketonuria) because the liver produces more than peripheral tissues use; the brain adapts to using acetoacetate as an energy source. During ketoemia, the concentration of acetoninic substances in the blood can reach 20 mM/l or higher.

The causes of ketoemia include:

• Activation of lipolysis and release of fatty acids
• Intense oxidation of fatty acids in cells
• Inhibition of lipid synthesis
• Inhibition of acetyl-CoA oxidation in hepatocytes
• Intensification of ketogenesis

When ketoemia begins, ketonuria usually follows, as the kidneys filter acetoninic substances well, leading to a hundredfold increase in their concentration in the urine.