Ketone body catabolism

DNA replication, RNA, genes, exons, introns, cloning Transcription and translation Gene regulation, mutation, recombinant DNA Cells, mitochondria, common catabolic pathway Phosphorylation, energy yield, conversion Glycosis, energy yield, catabolism Ketone bodies, catabolism Fourth hour exam... 

One suggestion to explain this discrepancy is that two pathways of fat catabolism are available and that ketone body formation is the resultant of only one type of breakdown.177 This latter type, also called the indirect fat utilization, 182 occurs in the liver the catabolism of fat in the muscle, called the -direct method, either involves no ketogenesis or the ketone bodies are immediately utilized and no accumulation occurs. 

Acetyl-CoA is at the product of fatty acid catabolism and may be derived from amino acids and carbohydrates (via pyruvate). Acetyl-CoA is the precursor of fatty acids, cholesterol and ketone bodies. 

In the brain, when ketones are metabolized to acetyl CoA, pyruvate dehydrogenase is inhibited. Glycolysis and subsequently glucose uptake in brain decreases. This important switch spares body protein (which otherwise would be catabolized to form glucose by gluconeogenesis in the liver) by allowing the brain to indirectly metabolize fetty acids as ketone bodies. 

The carbon skeletons of six amino acids are converted in whole or in part to pyruvate. The pyruvate can then be converted to either acetyl-CoA (a ketone body precursor) or oxaloacetate (a precursor for gluconeogenesis). Thus amino acids catabolized to pyruvate are both ke-togenic and glucogenic. The six are alanine, tryptophan, cysteine, serine, glycine, and threonine (Fig. 18-19). Alanine yields pyruvate directly on transamination with... 

FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin. Insulin stimulates conversion of dietary carbohydrates and proteins to fat. Individuals with diabetes mellitus lack insulin in uncontrolled disease, this results in diminished fatty acid synthesis, and the acetyl-CoA arising from catabolism of carbohydrates and proteins is shunted instead to ketone body production. People in severe ketosis smell of acetone, so the condition is sometimes mistaken for drunkenness (p. 909). 

When the blood glucose level falls and the liver s glycogen reserves are also exhausted, the liver still has the capacity to synthesize glucose via gluconeogenesis from amino acids that are supplied from protein breakdown. Under starvation conditions the liver forms increasing amounts of ketone bodies (see fig. 18.7). This is due to elevated concentrations of acetyl-CoA, which favor the formation of ketone bodies. The ketone bodies are secreted and used as a source of energy by other tissues, especially those tissues like the brain that cannot catabolize fatty acids directly. 

Excess acetate (C2) can be converted to the mobile ketone body energy source aceto-acetate (C4) and thence its reduced form hydroxybutyrate (C,) for transport throughout the body. Excess acetate can be carboxylated (via acetylCoA carboxylase) to form malonylCoA (C3), the donor for further C2 additions (with C02 elimination) in the anabolic synthesis of long chain fatty acids. Fatty acids are components of the phospholipids of cellular membranes and are also stored as triacylglycerols (triglycerides) for subsequent hydrolysis and catabolic fatty acid oxidation to yield reduced coenzymes and thence ATP (see Chapter 2). 

Amino acids can be classified as glycogenic or ketogenic- This classification refers to the products of catabolism (breakdown) of the amino acid in the body. Glycogenic amino acids can be converted to glucose, whereas ketogenic amino acids form ketone bodies. This classification is discussed in the Protein chapter. 

The starting material for kotonc body synthesis and catabolism, shown in Figure 4.65, is acctyl-CoA. Ketogenesis occurs in the mitochondria of the liver. Hence, ketone body synthesis is, for acetyl-CoA, an alternate fate to immediate oxidation in the Krebs cycle, Tiais pathway results in the formation of acetoacetate and p-hydroxybutyrate. Both appear in the bloodstream (the latter at higher concentrations) and are taken up by various organs, such as the brain and muscle. Here, they are converted back to acetyKloAand then oxidized in the Krebs cycle. 

NAD tends to be an electron acceptor in catabolic reactions involving the degradation of carbohydrates, fatty acids, ketone bodies, amino acids, and alcohol. NAD is used in energy-producing reactions. NADP, which is cytosolic, tends to be involved in biosynthetic reactions. Reduced NADP is generated by the pentose phosphate pathway (cytosolic) and used by cytosolic pathways, such as fatty acid biosynthesis and cholesterol synthesis, and by ribonucleotide reductase. The niacin coenzymes are used for two-electron transfer reactions. The oxidized form of NAD is NAD". There is a positive charge on the cofactor because the aromatic amino group is a quaternary amine. A quaternary amine participates in four... 

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