Disease relevance of Oat

• Ornithine aminotransferase (OAT), a mitochondrial matrix enzyme, is deficient in patients with gyrate atrophy of the choroid and retina [1].
• We found that an arginine-restricted diet substantially reduces plasma ornithine levels and completely prevents retinal degeneration in Oat(-/-) [2].
• This is evidenced by the activity of sensitive, biochemical markers of renal hypertrophy, namely arginase and ornithine aminotransferase (OAT), that responded with the increase and decrease of activities to testosterone treatment, respectively [3].
• The protective effects of combinations of 5-fluoromethylornithine (5FMOrn), a selective inhibitor of ornithine aminotransferase, and of compounds known to antagonize ammonia toxicity, were studied in acute, lethal ammonia intoxication in mice [4].
• Administration of 5-fluoromethylornithine (5FMOrn), a selective inactivator of ornithine aminotransferase (OAT), significantly reduced mortality, and it ameliorated most of the TAA-induced pathologic symptoms, such as hypothermia, decreased locomotor and exploratory behavior, pathologic liver function and amino acid patterns [5].

High impact information on Oat

• Colocalization in pericentral hepatocytes in adult mice and similarity in developmental expression pattern of ornithine aminotransferase and glutamine synthetase mRNA [6].
• In addition, we have used a panel of Chinese hamster-mouse hybrids to assign the murine Oat structural gene to mouse chromosome 7 [7].
• Gyrate atrophy of the choroid and retina is an autosomal recessive, blinding human disease caused by a deficiency of the mitochondrial matrix enzyme ornithine aminotransferase (OAT) [7].
• In H4Flox liver, GS, ornithine aminotransferase (OAT) and thyroid hormone-receptor beta1 (TRbeta1) were exclusively expressed in pericentral hepatocytes [8].
• A heritable variant of mouse liver ornithine aminotransferase (EC 2.6.1.13) induced by ethylnitrosourea [9].

Chemical compound and disease context of Oat

• To determine whether chronic, systemic reduction of ornithine can prevent this form of retinal degeneration, we used an arginine-restricted diet to maintain long term reduction of ornithine in a mouse model of OAT-deficiency (Oat(-/-)) produced by gene targeting [2].
• The specific activity of only ornithine aminotransferase (OAT), the rate-limiting enzyme in the conversion of ornithine to proline, increased in 2 weeks of hypertrophy [10].

Biological context of Oat

• Mapping of ornithine aminotransferase gene sequences to mouse chromosomes 7, X, and 3 [1].
• Others have shown that the expression of ornithine aminotransferase (OAT) rapidly decreases in the intestine at the same age when the AI-deficient animals die, indicating that this enzyme is critical to the maintenance of ornithine homeostasis, at least at this early stage of mouse development [11].
• Sequence of the promoter region of the mouse gene encoding ornithine aminotransferase [12].
• Localization of the ornithine aminotransferase gene and related sequences on two human chromosomes [13].
• Ornithine aminotransferase-related sequences map to two nonadjacent intervals on the human X chromosome short arm [14].

Anatomical context of Oat

• Evidence that interaction of hepatocytes with the collecting (hepatic) veins triggers position-specific transcription of the glutamine synthetase and ornithine aminotransferase genes in the mouse liver [15].
• A variant of ornithine aminotransferase from mouse small intestine [16].

Associations of Oat with chemical compounds

• Testosterone down-regulates ornithine aminotransferase gene and up-regulates arginase II and ornithine decarboxylase genes for polyamines synthesis in the murine kidney [17].
• We tried to find out whether testosterone treatment affects also the renal activities of enzymes participating in the formation and utilization of ornithine, specifically arginase and ornithine aminotransferase, and whether they are dependent on putrescine level [18].
• We established the developmental profile of the two intestinal mitochondrial enzymes, pyrroline 5-carboxylate synthase and ornithine aminotransferase, responsible for the conversion of glutamate to ornithine [19].
• Selective inactivation of ornithine aminotransferase (OAT) by 5-fluoromethylornithine raises endogenous ornithine concentrations so that citrulline formation is effectively catalysed by the aberrant OCT, in spite of its low affinity for ornithine [20].
• Finally, in the PST of females, L-arginine-derived ornithine may be a precursor for the renal production of L -glutamate and L-glutamine because high levels of AII, ornithine aminotransferase and glutamine synthetase are expressed in this nephron segment [21].

Other interactions of Oat

• Aberrations of ammonia metabolism in ornithine carbamoyltransferase-deficient spf-ash mice and their prevention by treatment with urea cycle intermediate amino acids and an ornithine aminotransferase inactivator [22].
• Phosphate deprivation of Hyp mice resulted in a 3-fold increase in the maximum velocity for 24-hydroxylase (n = 5; P < 0.001) accompanied by an increase in 24-hydroxylase immunoreactive protein relative to the level of ornithine aminotransferase [23].
• Interrelationships between ornithine, glutamate, and GABA. II. Consequences of inhibition of GABA-T and ornithine aminotransferase in brain [24].
• Protein profiles of amino acid metabolic enzymes suggest that accumulation of glutamine and glutamate in tissues of the aged SAMP8 may be due to hyperexpression of ornithine aminotransferase and/or glutamate dehydrogenase [25].

References