Ketone body metabolism

Note that only two of the ketone bodies are in fact ketones, and that acetone is an unintentional breakdown product resulting from the instability of acetoacetate at body temperature. Acetone is not available as fuel to any significant extent, and is thus a waste product. 

CNS tissues can use ketone bodies any time, the problem is the normally very low concentrations ( 0.3 mM) compared to glucose (about 4 mM). Since the Km s for both are similar, the CNS doesn t begin to use ketone bodies in preference to glucose until their concentration exceed s the concentration of glucose in the serum. 

Occurs in liver when acetyl CoA production exceeds the limits of its oxidation in the citric acid cycle--------------- starvation or uncontrolled diabetes. 

Mobilization of free fatty acids from fat depots 

Increased delivery of free fatty acids to the liver 

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Because glucose is the preferred fuel for the brain, an individual who experiences a rapid fall in glucose concentration leading to acute neuroglycopenia will initially feel confusion and may progress to coma and even death. In the event that the person survives 3-4 days, the brain can adapt its metabolism to utilize ketone bodies, metabolically derived from acetyl-CoA (see Figure 6.17), as a source of energy. 

Mitchell GA, Kassovska-Bratinova S, Boukaftane Y, Robert MF, Wang SP, Ashmarina L, Lambert M, Lapierre P, Potier E (1995) Medical aspects of ketone body metabolism. Clin Invest Med 18 193-216... 

Nosadini, R., Avogaro, A., Doria, A., Fioretto, P., Trevisan, R., Morocutti, A. (1989) Ketone body metabolism a physiological and clinical overview. Diabetes Metab. Rev. 5, 299-319. 

Source Data from Fenselau, A. Ketone body metabolism in normal and diabetic man. In Brownlee M, ed. Diabetes mellitus, Vol. III. New York Garland STPM Press, 1981, p. 145. 

Crabtree, B., Taylor, D.J., Coombs, J.E., Smith, R.A., Templer, S.P., Smith, G.H. 1981. The activities and intracellular distributions of enzymes of carbohydrate, lipid and ketone-body metabolism in lactating mammary glands from ruminants and non-ruminants. Biochem. 1. 196, 747-756. 

Mitchell GA, Fukao T Inborn errors of ketone body metabolism, in Scriver CR, Sly WS, et al. (eds) The Metabolic and Molecular Bases of Inherited Disease. 8th ed. McGraw-Hill, New York, 2001, pp. 2327-2356. 

Engel, F.L., Hewson, K., Cole, B.T. (1954). Carbohydrate and ketone body metabolism in the sodium fiuoroacetate poisoned rats. SFA diabetes. J. Am. Phys. 179 325-32. 

FIGURE 4,65 Synthesis, circulation, and de adatiun of ketone bodies. Ketone body metabolism involves synthesis in the mitochondria of the fiver, distribution via the bloodstream, and oxidation by the Krebs cycle in various organs, such as ihe brain and muscle,... 

Fery, F., and Balasse, E. O. (1966). Response of ketone body metabolism to eKcrdse during tran.sition from postabsorptive to fasted state. Am. I. Physiol. 250, E495-E501. 

Niacin is a water-soluble vitamin. The RDA of niacin for the adult man is 19 mg. Niacin is converted in the bi>dy to the cofactor nicotinamide adenine dinucleotide (NAD). NAD also exists in a phosphorylated form, NADP The phosphate group occurs on the 2-hydrr>xyl group of the AMP half of the coenzyme, NAD and NADP are used in the catalysis of oxidation and reduction reactions. These reactions are called redox reactions. NAD cycles between the oxidized form, NAD, and the reduced form, NADH + H. The coenzyme functions to accept and donate electrons. NADP behaves in a similar fashion. It occurs as NADP and NADPH + HT The utilization of NAD is illustrated in the sections on glycolysis, the malatc-aspartate shuttle, ketone body metabolism, and fatty acid oxidation. The utilization of NADP is illustrated in the sectirrns concerning fatty acid synthesis and the pentose phosphate pathway. 

The utilization of NAD is illustrated in the sections on glycolysis, the malate-aspartate shuttle, ketone body metabolism, and fatty acid oxidation. The utilization of NADP is illustrated in the sections concerning fatty acid synthesis and the pentose phosphate pathway. 

A deficiency purely in pantothenic acid has probably never occurred, except in controlled studies. Persons suffering from severe malnutrition would be expected to be deficient in the vitamin. Studies with animals have shown that consumption of a diet deficient in the vitamin results in a loss of appetite, slow growth, skin lesions, ulceration of the intestines, weakness, and eventually death. Pantothenic acid deficiency also results in the production of gray fur in animals whose fur is colored. Biochemical studies with deficient animals have revealed severe decreases in pantothenic acid levels in a variety of tissues, but only moderate declines in the levels of coenzyme A in liver and kidney and maintenance of coenz)nne A levels in the brain (Smith et ah, 1987). Some striking defects in glycogen and ketone body metabolism have been noted in pantothenic acid-deficient animals. 

J2. Jacobson, B. E., Blanchaer, M. C., and Wrogemann, K., Defective respiration and oxidative phosphorylation in muscle mitochondria of hamsters in the late stages of hereditary muscular dystrophy. Can. J. Biochem. 48, 1037-1042 (1970), J3. Jenkins, K. J., Ketone body metabolism in nutritional myopathy. Can. J. Biochem. 42, 1153-1160 (1964). 

Effect of increased fatty-acid availability on muscle metabolism. The effect of fatty acids and ketone-body metabolism on glucose metabolism in the muscle is shown above. The major effect is a decrease of glucose utilization by the muscle. Negative aspects on this metabolism are shown in purple (for more detail, see the text). 

Acetyl-CoA is an "activated" two carbon compound found in many central metabolic pathways, including the citric acid cycle, the glyoxylate cycle, fatty acid synthesis, fatty acid oxidation, isoprene metabolism, amino sugar metabolism, ketone body metabolism, and cholesterol biosynthesis. The term "activated" used to describe the compound comes partly from the nature of the high energy... 

Acetoacetyl-CoA is an intermediate in fatty acid oxidation, cholesterol biosynthesis and ketone body metabolism (ketogenesis) participating in the following reactions ... 

Acetoacetate + NADH + H+ <=> / -Hydroxybutyrate + NAD The reaction is important in ketone body metabolism. 

Acetone is produced in the body as a product of ketone body metabolism. 

The heart uses a variety of fuels-mainly fatty acids but also glucose, lactate, and ketone bodies. Metabolism of heart muscle differs from that of skeletal muscle in three important respects. 

Fukao, T., G. D. Lopaschuk, and G. A. Mitchell. 2004. Pathways and control of ketone body metabolism On the fringes of lipid metabolism. Prostaglandins Leukotrienes and Essential Fatty Acids 70 243-251. 

Zammit, V.A. (1994) Diabetes Rev. 2, 132-155. Regulation of ketone body metabolism. A cellular perspective. 

S0vik O. Mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency an inborn error of isoleudne and ketone body metabolism. J Inherit Metab Dis. 1993 16(l) 46-54. 

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