Lysine oxidation

In addition, the concept of linear responses to graded levels of nutrient input is not consistent with the kinetics of enzymes or enzyme systems. A curved response for individual animals would be expected just as a Michaelis-Menton relationship is expected with increasing substrate concentration for an enzyme. Curved responses have been observed when lysine a-ketoglutarate reductase activity (a simple enzyme system) and lysine oxidation to CO2 (a more complicated pathway) were measured (Blemings et al, 1994). Lysine metabolism in liver homogenates may not be directly related to whole animal responses (an animal is not a big enzyme). An animal is a system of pools and fluxes, however, and there does not appear to be a set of discrete on/off switches. 

Goodman, S.I. and Frerman, F.E. (1995) Organic acidemias due to defects in lysine oxidation 2-ketoadipic acidemia and glutaric acidemia, in The Metabolic and Molecular Bases of Inherited Disease (eds C.R. Scriver, A.L. Beaudet, W.S. Sly and D. Valle), McGraw-Hill, New York, pp. 2195-2240. 

Sundower Seed. Compared to the FAO/WHO/UNU recommendations for essential amino acids, sunflower proteins are low in lysine, leucine, and threonine for 2 to 5-year-olds but meet all the requirements for adults (see Table 3). There are no principal antinutritional factors known to exist in raw sunflower seed (35). However, moist heat treatment increases the growth rate of rats, thereby suggesting the presence of heat-sensitive material responsible for growth inhibitions in raw meal (72). Oxidation of chlorogenic acid may involve reaction with the S-amino group of lysine, thus further reducing the amount of available lysine. 

Ascorbic acid is involved in carnitine biosynthesis. Carnitine (y-amino-P-hydroxybutyric acid, trimethylbetaine) (30) is a component of heart muscle, skeletal tissue, Uver and other tissues. It is involved in the transport of fatty acids into mitochondria, where they are oxidized to provide energy for the ceU and animal. It is synthesized in animals from lysine and methionine by two hydroxylases, both containing ferrous iron and L-ascorbic acid. Ascorbic acid donates electrons to the enzymes involved in the metabohsm of L-tyrosine, cholesterol, and histamine (128). 

A -Pyrroline has been prepared in low yield by oxidation of proline with sodium hypochlorite (71), persulfate (102), and periodate (103). A -Pyrroline and A -piperideine are products of enzymic oxidation via deamination of putrescine and cadaverine or ornithine and lysine, respectively (104,105). This process plays an important part in metabolism and in the biosynthesis of various heterocyclic compounds, especially of alkaloids. 

Lipoic acid exists as a mixture of two structures a closed-ring disulfide form and an open-chain reduced form (Figure 18.33). Oxidation-reduction cycles interconvert these two species. As is the case for biotin, lipoic acid does not often occur free in nature, but rather is covalently attached in amide linkage with lysine residues on enzymes. The enzyme that catalyzes the formation of the lipoamide nk.2Lg c requires ATP and produces lipoamide-enzyme conjugates, AMP, and pyrophosphate as products of the reaction. 

FIGURE 18.33 The oxidized and reduced forms of lipoic acid and the structure of the lipoic acid-lysine conjugate. 

H2/Pd-C. If hydrogenation is carried out in the presence of (B0C)20, the released amine is directly converted to the BOC derivative. The formation of A-methylated lysines during the hydrogenolysis of a Z group has been observed with MeOH/DMF as the solvent. Formaldehyde derived oxidatively from methanol is the source of the methyl carbon. ... 

Figure 2. Mechanism of PDH. The three different subunits of the PDH complex in the mitochondrial matrix (E, pyruvate decarboxylase E2, dihydrolipoamide acyltrans-ferase Ej, dihydrolipoamide dehydrogenase) catalyze the oxidative decarboxylation of pyruvate to acetyl-CoA and CO2. E, decarboxylates pyruvate and transfers the acetyl-group to lipoamide. Lipoamide is linked to the group of a lysine residue to E2 to form a flexible chain which rotates between the active sites of E, E2, and E3. E2 then transfers the acetyl-group from lipoamide to CoASH leaving the lipoamide in the reduced form. This in turn is oxidized by E3, which is an NAD-dependent (low potential) flavoprotein, completing the catalytic cycle. PDH activity is controlled in two ways by product inhibition by NADH and acetyl-CoA formed from pyruvate (or by P-oxidation), and by inactivation by phosphorylation of Ej by a specific ATP-de-pendent protein kinase associated with the complex, or activation by dephosphorylation by a specific phosphoprotein phosphatase. The phosphatase is activated by increases in the concentration of Ca in the matrix. The combination of insulin with its cell surface receptor activates PDH by activating the phosphatase by an unknown mechanism.

The Jing group investigated their poly(L-lysine)-6-poly(L-phenylalanine) vesicles for the development of synthetic blood, since PEG-lipid vesicles were previously used to encapsulate hemoglobin to protect it from oxidation and to increase circulation time. They extended this concept and demonstrated that functional hemoglobin could be encapsulated into their vesicles. The same polypeptide material was also used to complex DNA, which caused the vesicles to lose their... 

Figure 17-5. Oxidative decarboxylation of pyruvate by the pyruvate dehydrogenase complex. Lipoic acid is joined by an amide link to a lysine residue of the transacetylase component of the enzyme complex. It forms a long flexible arm, allowing the lipoic acid prosthetic group to rotate sequentially between the active sites of each of the enzymes of the complex. (NAD nicotinamide adenine dinucleotide FAD, flavin adenine dinucleotide TDP, thiamin diphosphate.)...

After secretion from the cell, certain lysyl residues of tropoelastin are oxidatively deaminated to aldehydes by lysyl oxidase, the same enzyme involved in this process in collagen. However, the major cross-links formed in elastin are the desmosines, which result from the condensation of three of these lysine-derived aldehydes with an unmodified lysine to form a tetrafunctional cross-hnk unique to elastin. Once cross-linked in its mature, extracellular form, elastin is highly insoluble and extremely stable and has a very low turnover rate. Elastin exhibits a variety of random coil conformations that permit the protein to stretch and subsequently recoil during the performance of its physiologic functions. 

Yoshioka T, JA Krauser, FP Guengerich (2002) Tetrachloroethylene oxide hydrolytic products and reactions with phosphate and lysine. Chem Res Toxicol 15 1096-1105. 

The reactions described so far do not require the involvement of the apo-B protein, neither would they necessarily result in a significant amount of protein modification. However, the peroxyl radical can attack the fatty acid to which it is attached to cause scission of the chain with the concomitant formation of aldehydes such as malondialdehyde and 4-hydroxynonenal (Esterbauer et al., 1991). Indeed, complex mixtures of aldehydes have been detected during the oxidation of LDL and it is clear that they are capable of reacting with lysine residues on the surface of the apo-B molecule to convert the molecule to a ligand for the scavenger receptor (Haberland etal., 1984 Steinbrecher et al., 1989). In addition, the lipid-derived radical may react directly with the protein to cause fragmentation and modification of amino acids. 

Steinbrecher, U.P. (1987). Oxidation of human low density lipoprotein results in derivatisation of lysine residues of apolipoprotein B by lipid peroxidation decomposition products. J. Biol. Chem. 262, 3603-3608. 

Materials and Purification. Chemicals were purchased from Aldrich chemical company and used as received unless otherwise noted 1,1,1,3,3,3-hexamethyl disilazane, ethylene glycol, triphosgene, poly(ethylene oxide) (MW = 600), poly(tetramethylene oxide) (MW = 1000), poly(caprolactonediol) (MW = 530), toluene diisocyanate (TDI), anhydrous ethanol (Barker Analyzed), L-lysine monohydride (Sigma) and methylene bis-4-phenyl isocyanate (MDI) (Kodak). Ethyl ether (Barker Analyzer), triethylamine and dimethyl acetamide were respectively dried with sodium, calcium hydride and barium oxide overnight, and then distilled. Thionyl chloride and diethylphosphite were distilled before use. 

Interestingly, the nucleophilic addition of water in the sequence of events giving rise to 41 represents a relevant model system for investigating the mechanism of the generation of DNA-protein cross-links under radical-mediated oxidative conditions [80, 81]. Thus, it was shown that lysine tethered to dGuo via the 5 -hydroxyl group is able to participate in an intramolecular cyclization reaction with the purine base at C-8, subsequent to one electron oxidation [81]. 

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