Formation of Ketone Bodies

It is well established that in humans and other mammals the only organ that contributes significant amounts of ketone bodies to the blood is the liver; this organ, unlike peripheral tissues, is unable to utilize ketone bodies to any appreciable extent. More recently it has been found that during the suckling period (high-fat diet) the intestine also has the capacity (about 10% of the liver) to produce ketone bodies. Whether ketone bodies are used in situ or are transported via the portal blood to supplement the existing hyperketonemia is an open question.

The main blood-borne substrates for the synthesis of ketone bodies (ketogenesis) are the nonesterified fatty acids; others of lesser importance are the branched-chain amino acids, leucine and isoleucine. In addition, acetate (sources: intestinal fermentation, in vinegar or an oxidation product of ethanol) is a ketogenic substrate.

Long-chain fatty acids contained in dietary lipids do not enter the portal blood directly but are esterified in the intestinal cells, packaged with proteins and phos-pholipids to form chylomicrons (large lipoproteins), and transported via the lymphatic system to the thoracic duct where they enter the blood. In contrast, the short- and medium-chain fatty acids (below Ci4) contained in dairy products or in clinical medium-chain triacylglycerol preparations are directly absorbed as the respective fatty acids and are transported to the liver via the portal blood (Figure 1). The long-chain

Figure 1 Intertissue fluxes of substrates in the suckling neonate. Thickness of line denotes rate of flux.

fatty acids in the plasma are bound to albumin and are released from adipose tissue triacylglycerol stores by the process of lipolysis.

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