BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 14. LIPID METABOLISM

14.9. Ketone Body Metabolism

Ketone Bodies, which include acetoacetate, β-hydroxybutyrate, and acetone, are synthesized in the Liver from acetyl-CoA, one of the three principal intermediate metabolites generated during The breakdown of CARBOHYDRATES, ketogenic Amino Acids, and Fatty acids.

The precursor for Ketone Body Synthesis is 3-hydroxy-3-methylglutaryl-CoA, a central intermediate product of Cholesterol Biosynthesis. During ketone body formation, 3-hydroxy-3-methylglutaryl-CoA is cleaved by hydroxymethylglutaryl-CoA lyase into acetoacetate and acetyl-CoA. Reduction of acetoacetate by the action of β-hydroxybutyrate dehydrogenase yields β-hydroxybutyrate, whereas spontaneous non-enzymatic decarboxylation of acetoacetate produces acetone (Fig. 14.12).

In the liver of a healthy individual, a small amount of acetoacetate and β-hydroxybutyrate (with the latter predominating) is synthesized daily, released into the bloodstream, and transported to peripheral Tissues. Ketone bodies are utilized in cardiac and skeletal Muscles, as well as in the Kidneys, by oxidizing β-hydroxybutyrate to acetoacetate and subsequently cleaving the latter into two molecules of acetyl-CoA, which are oxidized in The Tricarboxylic Acid Cycle. Consequently, ketone bodies, which are continuously produced in the liver, do not function as intermediate metabolites of lipid turnover, but rather as an end product and an additional energy source for peripheral

tissues. Under conditions of prolonged total fasting, ketone bodies—the products of Fatty acid oxidation—become the sole energy source even for Brain Cells.

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Fig. 14.12. Scheme of ketone body Synthesis and degradation in animal and human tissues

During prolonged fasting or diabetes, a decrease in mitochondrial oxaloacetate levels triggers enhanced synthesis of ketone bodies, leading to their elevated concentration in the Blood (ketonemia), which results in acidosis and Ketosis. Under these conditions, acetoacetate undergoes decarboxylation to form acetone, which cannot be utilized by tissues and is excreted via urine and exhaled air.