Lysine metabolic role

Flodin NW. The metabolic roles, pharmacology, and toxicology of lysine. J Am Coll Nutr 1997 16 7-21. 

Pyridoxal phosphate (4) is the most important coenzyme in amino acid metabolism. Its role in transamination reactions is discussed in detail on p. 178. Pyridoxal phosphate is also involved in other reactions involving amino acids, such as decarboxylations and dehydrations. The aldehyde form of pyridoxal phosphate shown here (left) is not generally found in free form. In the absence of substrates, the aldehyde group is covalently bound to the e-amino group of a lysine residue as aldimine ( Schiffs base ). Pyridoxamine phosphate (right) is an intermediate of transamination reactions. It reverts to the aldehyde form by reacting with 2-oxoacids (see p. 178). 

Carnitine, L-3-hydroxy-4-(trimethylammonium)butyrate, is a water-soluble, tri-methylammonium derivative of y-amino-jS-hydroxybutyric acid, which is formed from trimethyllysine via y-butyrobetaine [40]. About 75% of carnitine is obtained from dietary intake of meat, fish, and dairy products containing proteins with trimethyllysine residues. Under normal conditions, endogenous synthesis from lysine and methionine plays a minor role, but can be stimulated by a diet low in carnitine. Carnitine is not further metabolized and is excreted in urine and bile as free carnitine or as conjugated carnitine esters [1, 41, 42]. Adequate intracellular levels of carnitine are therefore maintained by mechanisms that modulate dietary intake, endogenous synthesis, reabsorption, and cellular uptake. 

Eight enzyme-catalyzed reactions are involved in the conversion of acetyl-CoA into fatty acids. The first reaction is catalyzed by acetyl-CoA carboxylase and requires ATP. This is the reaction that supplies the energy that drives the biosynthesis of fatty acids. The properties of acetyl-CoA carboxylase are similar to those of pyruvate carboxylase, which is important in the gluconeogenesis pathway (see chapter 12). Both enzymes contain the coenzyme biotin covalently linked to a lysine residue of the protein via its e-amino group. In the last section of this chapter we show that the activity of acetyl-CoA carboxylase plays an important role in the control of fatty acid biosynthesis in animals. Regulation of the first enzyme in a biosynthetic pathway is a strategy widely used in metabolism. 

Alkaloid metabolism in lupine was proved by Wink and Hartmann to be associated with chloroplasts (34). A series of enzymes involved in the biosynthesis of lupine alkaloids were localized in chloroplasts isolated from leaves of Lupinus polyphylls and seedlings of L. albus by differential centrifugation. They proposed a pathway for the biosynthesis of lupanine via conversion of exogenous 17-oxosparteine to lupanine with intact chloroplasts. The biosynthetic pathway of lupinine was also studied by Wink and Hartmann (35). Two enzymes involved in the biosynthesis of alkaloids, namely, lysine decarboxylase and 17-oxosparteine synthetase, were found in the chloroplast stoma. The activities of the two enzymes were as low as one-thousandth that of diaminopimelate decarboxylase, an enzyme involved in the biosynthetic pathway from lysine to diaminopimelate. It was suggested that these differences are not caused by substrate availability (e,g., lysine concentration) as a critical factor in the synthesis of alkaloids. Feedback inhibition would play a major role in the regulation of amino acid biosynthesis but not in the control of alkaloid formation. 

Biochemical Functions. Ascorbic acid has various biochemical fimctions, involving, for example, coUagen synthesis, immune fimction, drug metabohsm, folate metabolism, cholesterol catabolism, iron metabolism, and carnitine biosynthesis. Clear-cut evidence for its biochemical role is available only with respect to coUagen biosynthesis (hydroxylation of prolin and lysine). In addition, ascorbic acid can act as a reducing agent and as an effective antioxidant. Ascorbic acid also interferes with nitrosamine formation by reacting directly with nitrites, and consequently may potentially reduce cancer risk. 

Feedback Regulation. Feedback regulation also appears to play a role in secondary metabolism. It was shown many years ago that chloramphenicol inhibits its own production at concentrations nontoxic for growth of Streptomyces venezuelae (Legator and Gottlieb, 1953). Addition of 6-methylsalicylic acid to idiophase mycelium of P. urticae inhibits its own synthesis (Bu Lock and Shepherd, 1968). Stimulation of carotenoid overproduction by )8-ionone in Phycomyces blakesleeanus appears to be due to its ability to interfere with normal feedback inhibition (Reyes et al, 1964). The inhibition of penicillin production by lysine (Demain, 1957) seems to be due to feedback regulation by the amino acid of a branched pathway (Fig. 6) leading to both lysine and... 

Dichloroacetylated mitochondrial and cytosolic proteins (7V -[dichloroacetyl]-L-lysine) detected in the kidneys of tetrachloroethylene-treated Wistar rats suggests that the glutathione, -lyase pathway may have a role in the renal toxicity of tetrachloroethylene (Bimer et al. 1994). How the differences in tetrachloroethylene metabolism between humans, rats, and mice affect toxicity is discussed in Section 2.4.2. 

Biosynthesis metabolism Asp is formed from oxaloacetic acid by aspartate aminotransferase (EC 2.6.1.1) and serves as starting material in the biosyntheses of threonine, methionine, and lysine. The first step is catalysed by aspartate kinase (EC 2.7.24) which only occurs in plants and microorganisms. This enzyme exists as 3 isozymes in Escherichia coli and exhibits a typical example of feedback regulation. Asp plays a central role in the biosyntheses of pyrimidines and purines. In the urea cycle Asp condenses with " citrulline to aigininosuccinate, a stimulating neuro-transmitter. ... 

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