Reactions of cysteamine and other amine metabolites with glyoxylate and oxygen catalyzed by mammalian D-amino acid oxidase.

Abstract

, and Lcysteine ethyl ester. Notable physiological amines that do not support a rapid 02 reaction under the above conditions include histamine, serotonin, epinephrine, norepinephrine, spermidine, spermine, and cadaverine. A more detailed kinetic investigation of the reactions involving the first four reactive amines listed above indicated that the cysteamine reaction proceeds at a rapid rate even when cysteamine and glyoxylate are present at less than millimolar concentrations, but greater than millimolar concentrations are needed in the other amine reactions in order to observe a reasonable rate. At low concentrations and pH 7.4, the cysteamine-glyoxylate substrate (presumably thiazolidine-2-carboxylic acid) reacts an order of magnitude faster than any other known D-amino acid oxidase substrate. Considerable circumstantial evidence suggests that the reaction involving cysteamine is occurring physiologically, but the reactions of other amines would be occurring in the cell at a very low rate, if at all. It is proposed that the product of the enzymic reaction may be a metabolic effector that can modify the reactivity of proteins or nucleic acids by covalent attachment. Although the presence of D-amino acid oxidase [D-aminoacid:oxygen oxidoreductase (deaminating), EC 1.4.3.3; D-AA oxidase] activity in mammalian tissues has been known (1, 2) since the early 1930s, the physiological function of the enzyme has remained unknown. The specific reaction catalyzed (3) by the oxidase is the transhydrogenation shown in Eq. I.

Thiamine Deficiency and Glyoxylic Acid

“…Al though we found that high concentrations of glyoxylate (in the mM range) inhibit the oxi dation of several substrates [see also 8,9,18] and the synaptosomal uptake and release of several neurotransmitters, there were no con sistent effects observed when the glyoxylate levels were lowered toward those reported by Liang [3] to occur in thiamine-deficient rats (in the ]iM range). Studies on in vivo effects of glyoxylate are hampered by the fact that there are no reliable methods for estimating low levels of glyoxylate in tissue samples [16,19,20],…”

“…Glyoxylate can inhibit several enzyme activities [10,18], but the levels of glyoxylate required for signifi cant effects are much greater than even the highest levels reported for thiamine-deficient tissues [3][4][5], There is also the major problem of simply defining the cellular glyoxylate pool. Glyoxylate is a chemically highly reac tive species which can form covalent com pounds with several types of metabolites commonly found in cells, such as sulfhydryl, amino and guanido compounds and keto acids [18,20,[35][36][37][38], There arc various methods for measuring free glyoxylate in aqueous solvents [16,26,[39][40][41][42]], but it is unclear how many of the glyoxylate addition products react in these systems. If free labeled glyoxylate is added to urine samples, several unidentified labeled compounds are formed in some but not all cases [ 16,26], These com plications render the chemical or enzymic estimation of glyoxylate in biological materi als extremely difficult if not impossible [16,19,26,40],…”

Physiological functions of D-amino acid oxidases: from yeast to humans

“…Rat -Regulation of intracellular levels of oxalate acting on D-thiazolinidine-2-carboxylic acid [127,128] -Elimination of D-amino acids in kidney -DAAO could be involved in D-Ser-induced nephrotoxicity [121,122,146] Mouse -Modulation of NMDA receptor functionality via D-Ser metabolism -A number of information have been gathered using mutant mice lacking of DAAO activity [142,152] Human -Component of an antibacterial system in neutrophilic leukocytes [89] -Elimination of D-amino acids in kidney -Modulation of D-Ser in brain and thus of NMDA receptors functionality -An hyperactivity of DAAO in the brain (e.g., by pLG72 binding) may result in a local decrease of D-Ser and give a predisposition to schizophrenia [20] Cell. Mol.…”

Effects of Glyoxylate on Photosynthesis by Intact Chloroplasts

“…Fructose-P2 phosphatase is also activated by thioredoxin-dependent reduction (4) and inhibited by H202 oxidation of the sensitive sulfhydryl groups of the enzyme (5). Glyoxylate is amines (8), and might also inhibit fructose-P2 phosphatase directly or by interfering with thioredoxin-dependent activation. However …”