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Biomedicine & Pharmacotherapy =... Feb 2017Ornithine is a non-essential amino acid produced as an intermediate molecule in urea cycle. It is a key substrate for the synthesis of proline, polyamines and... (Review)
Review
Ornithine is a non-essential amino acid produced as an intermediate molecule in urea cycle. It is a key substrate for the synthesis of proline, polyamines and citrulline. Ornithine also plays an important role in the regulation of several metabolic processes leading to diseases like hyperorithinemia, hyperammonemia, gyrate atrophy and cancer in humans. However, the mechanism of action behind the multi-faceted roles of ornithine is yet to be unraveled completely. Several types of cancers are also characterized by excessive polyamine synthesis from ornithine by different rate limiting enzymes. Hence, in this review we aim to provide extensive insights on potential roles of ornithine in many of the disease related cellular processes and also on the structural features of ornithine interacting proteins, enabling development of therapeutic modalities.
Topics: Animals; Humans; Metabolic Diseases; Ornithine; Polyamines; Proline; Protein Binding; Protein Structure, Secondary
PubMed: 27978498
DOI: 10.1016/j.biopha.2016.12.024 -
FEMS Microbiology Letters Oct 2012Ornithine lipids (OLs) are phosphorus-free membrane lipids that are widespread in eubacteria, but absent from archaea and eukaryotes. They contain a 3-hydroxy fatty acyl... (Review)
Review
Ornithine lipids (OLs) are phosphorus-free membrane lipids that are widespread in eubacteria, but absent from archaea and eukaryotes. They contain a 3-hydroxy fatty acyl group attached in amide linkage to the α-amino group of the amino acid ornithine. A second fatty acyl group is ester-linked to the 3-hydroxy position of the first fatty acid. About 25% of the bacterial species whose genomes have been sequenced are predicted to have the capacity to form OLs. Distinct OL hydroxylations have been described in the ester-linked fatty acid, the amide-linked fatty acid, and the ornithine moiety. These modifications often seem to form part of a bacterial stress response to changing environmental conditions, allowing the bacteria to adjust membrane properties by simply modifying already existing membrane lipids without the need to synthesize new lipids.
Topics: Bacteria; Bacterial Proteins; Biological Transport; Lipids; Ornithine
PubMed: 22724388
DOI: 10.1111/j.1574-6968.2012.02623.x -
Nutrition (Burbank, Los Angeles County,... 1998
Review
Topics: Amino Acids; Humans; Immunity, Cellular; Nutritional Support; Ornithine; Wounds and Injuries
PubMed: 9834933
DOI: 10.1016/s0899-9007(98)00118-x -
Current Drug Targets Sep 2000Ornithine-delta-aminotransferase (OAT) (EC 2.6.1.13) is a pyridoxal-5' phosphate dependent mitochondrial matrix enzyme. It controls the L-ornithine (Orn) level in... (Review)
Review
Ornithine-delta-aminotransferase (OAT) (EC 2.6.1.13) is a pyridoxal-5' phosphate dependent mitochondrial matrix enzyme. It controls the L-ornithine (Orn) level in tissues by catalysing the transfer of the delta-amino group of Orn to 2-oxoglutarate. The products of this reaction are L-glutamate-gamma-semialdehyde and L-glutamate. Among the compounds known to inhibit (or inactivate) OAT, only L-canaline and (SS)-5-(fluoromethyl)ornithine [(SS)-5FMOrn] are selective for OAT. Treatment of laboratory animals with 5FMOrn causes a dramatic accumulation of Orn in most tissues and organs, and the enhanced formation of urea due to saturation of ornithine:carbamoyltransferase with its substrate. The enhancement of urea formation by increased endogenous levels of Orn is comparable with that produced by large doses of Orn and arginine, a treatment known to enhance the detoxification of ammonia. However, protection to lethal doses of ammonium salts by exogenous Orn is rapidly fading. In contrast, inactivation of OAT by a small dose of 5FMOrn renders a long-lasting protective effect against various forms of hyperammonemic states. Among these the reduction of ammonia concentrations in blood and tissues, and the reduction of the pathologic excretion of orotic acid to normal levels in mice with hereditary defects of the urea cycle, were most impressive. In human hereditary OAT deficiency the elevated intraocular concentrations of Orn are considered to be a cause of gyrate atrophy. This is presumably the reason, why OAT has not been considered as a therapeutically useful target. Chronic inactivation of OAT by repeated administration of 5FMOrn, caused elevated intraocular Orn concentrations, but this treatment had no effect on the function and histology of the visual system, or the behaviour of adult mice. The confirmation of this and related observations in higher species will show, whether OAT inactivation has potentials in the treatment of hyperammonemic states.
Topics: Ammonia; Animals; Biogenic Polyamines; Brain; Chorioretinitis; Enzyme Inhibitors; Humans; Hyperammonemia; Kidney; Liver; Mice; Ornithine; Ornithine-Oxo-Acid Transaminase; Thioacetamide; Urea
PubMed: 11465067
DOI: 10.2174/1389450003349254 -
The British Journal of Nutrition Sep 2011We reviewed the literature on ornithine supplementation and related topics. Nutritionists and physicians have reported that ornithine supplementation is useful.... (Review)
Review
We reviewed the literature on ornithine supplementation and related topics. Nutritionists and physicians have reported that ornithine supplementation is useful. Paediatricians and biochemists have reported that ornithine is supplemented for NH(3) detoxification in the hyperornithinaemia-hyperammonaemia-homocitrullinuria (HHH) syndrome. In contrast, ophthalmic researchers have reported retinotoxicity associated with high-dose ornithine. In vivo and in vitro experiments have shown that high concentrations of ornithine or its metabolites are toxic to the retinal pigment epithelial (RPE) cells. Long-term (exceeding a few years) and high concentrations (exceeding 600 μmol/l) of ornithine in the blood induce retinal toxicity in gyrate atrophy of the choroid and retina (GA). Intermittent high levels of ornithine do not lead to retinal lesions. Constant blood ornithine levels between 250 and 600 μmol/l do not induce retinal lesions or cause a very slowly progressive retinal degeneration. Blood ornithine levels below 250 μmol/l do not produce retinal alteration. We concluded that short-term, low-dose or transient high-dose ornithine intake is safe for the retina; its nutritional usefulness and effect on NH(3) detoxification are supported by many researchers, but the effect may be limited; and long-term, high-dose ornithine intake may be risky for the retina. Patients with GA should avoid taking ornithine; amino acid supplementation should be administered carefully for patients with the HHH syndrome, relatives of patients with GA (heterozygotes) and subjects with RPE lesions; and blood ornithine levels and retinal conditions should be evaluated in individuals taking long-term, high-dose ornithine.
Topics: Animals; Dietary Supplements; Dose-Response Relationship, Drug; Haplorhini; Heterozygote; Humans; Hyperammonemia; Mice; Models, Biological; Ornithine; Rats; Rats, Sprague-Dawley; Retina; Retinal Degeneration; Retinal Pigment Epithelium; Urea Cycle Disorders, Inborn
PubMed: 21767450
DOI: 10.1017/S0007114511003291 -
Advances in Enzyme Regulation 1985Ornithine decarboxylase is a key enzyme in polyamine synthesis and growth of mammalian cells. In this chapter I review recent reports on the purification and properties... (Review)
Review
Ornithine decarboxylase is a key enzyme in polyamine synthesis and growth of mammalian cells. In this chapter I review recent reports on the purification and properties of the pure enzyme, and on the localization, synthesis and regulation of the enzyme in the cell. The use of monospecific antibodies, radiolabeled irreversible inhibitors and cDNA clones for studying enzyme localization, turnover and regulation, is briefly described. This first part is meant to serve as a basis for the analysis of ornithine decarboxylase as a target of chemotherapy. A selection of the most potent inhibitors of ornithine decarboxylase is presented and the effects of some of these in cell culture, in animals and in the clinical setting are reviewed.
Topics: Animals; Antineoplastic Agents; Cells, Cultured; Cloning, Molecular; DNA; Drug Resistance; Eflornithine; Humans; Mice; Neoplasms; Ornithine; Ornithine Decarboxylase; Ornithine Decarboxylase Inhibitors; Protein Biosynthesis; Subcellular Fractions
PubMed: 3939094
DOI: 10.1016/0065-2571(85)90072-x -
International Journal of Molecular... Jan 2022Advanced glycation end products (AGEs) are associated with diabetes and its complications. AGEs are formed by the non-enzymatic reactions of proteins and reducing...
Advanced glycation end products (AGEs) are associated with diabetes and its complications. AGEs are formed by the non-enzymatic reactions of proteins and reducing sugars, such as glucose and ribose. Ribose is widely used in glycation research as it generates AGEs more rapidly than glucose. This study analyzed the AGE structures generated from ribose-modified protein by liquid chromatography-quadrupole time-of-flight mass spectrometry. Among these AGEs, -(5-hydro-5-methyl-4-imidazolone-2-yl)-ornithine (MG-H1) was the most abundant in ribose-glycated bovine serum albumin (ribated-BSA) among others, such as -(carboxymethyl) lysine, -(carboxyethyl) lysine, and -(carboxymethyl) arginine. Surprisingly, MG-H1 was produced by ribated-BSA in a time-dependent manner, whereas methylglyoxal levels (MG) were under the detectable level. In addition, Roxb. hot water extract (TBE) possesses several anti-oxidative compounds, such as ellagic acid, and has been reported to inhibit the formation of MG-H1 in vivo. Thus, we evaluated the inhibitory effects of TBE on MG-H1 formation using ribose- or MG-modified proteins. TBE inhibited MG-H1 formation in gelatin incubated with ribose and ribated-BSA, but not in MG-modified gelatin. Furthermore, MG-H1 formation was inhibited by diethylenetriaminepentaacetic acid. These results demonstrated that ribose reacts with proteins to generate Amadori compounds and form MG-H1 via oxidation.
Topics: Animals; Cattle; Gelatin; Glycosylation; Imidazoles; Ornithine; Oxidation-Reduction; Protein Processing, Post-Translational; Pyruvaldehyde; Ribose; Serum Albumin, Bovine
PubMed: 35163152
DOI: 10.3390/ijms23031224 -
Nutrition Reviews Apr 1995Ornithine oxoglutarate (OGO) has been previously demonstrated to improve nutrition status in burn and trauma patients. Recently, OGO supplementation was shown to improve... (Review)
Review
Ornithine oxoglutarate (OGO) has been previously demonstrated to improve nutrition status in burn and trauma patients. Recently, OGO supplementation was shown to improve nutrition status, ameliorate quality of life, and reduce health care costs when given to elderly patients soon after discharge from the hospital.
Topics: Aged; Aging; Burns; Humans; Nutritional Status; Ornithine; Wounds and Injuries
PubMed: 7624064
DOI: 10.1111/j.1753-4887.1995.tb01527.x -
The Journal of Nutrition Oct 2004Ornithine alpha-ketoglutarate (OKG) is a salt formed of 2 molecules of ornithine and 1 alpha-ketoglutarate. Its administration improves nutritional status in chronically... (Review)
Review
Ornithine alpha-ketoglutarate (OKG) is a salt formed of 2 molecules of ornithine and 1 alpha-ketoglutarate. Its administration improves nutritional status in chronically malnourished (e.g., elderly) and acutely malnourished patients (especially burn and trauma patients). There is evidence that OKG activity is not the simple addition of the effects of ornithine (Orn) and alpha-ketoglutarate (alphaKG), because the presence of both moieties is required to induce the generation of key metabolites such as glutamine, proline, and arginine (Arg), whereas this does not occur when one or the other is given separately. This observation is related to the fact that the main feature of Orn at the whole-body level is to be metabolized through the Orn aminotransferase-dependent pathway, whereas the simultaneous administration of Orn and alphaKG saturates this pathway, diverting Orn toward metabolism into Arg. For years, OKG activity has been associated with its ability to induce the secretion of anabolic hormones, such as insulin and growth hormone, and to increase glutamine and polyamine synthesis. Recent studies using chemical inhibitors of nitric oxide synthase (NOS) suggest that nitric oxide derived from Arg could be partly involved in OKG activity. The use of genetically modified animals (i.e., knockout for NOS expression) is required to confirm this hypothesis.
Topics: Animals; Arginine; Humans; Nitric Oxide; Ornithine; Prodrugs
PubMed: 15465801
DOI: 10.1093/jn/134.10.2858s -
Metabolic Brain Disease Sep 1993The vertebrate brain has the machinery to transport arginine and ornithine, and to form within nerve endings from these amino acids glutamate and GABA, the major... (Review)
Review
The vertebrate brain has the machinery to transport arginine and ornithine, and to form within nerve endings from these amino acids glutamate and GABA, the major excitatory and inhibitory neurotransmitters. Ornithine aminotransferase is a key enzyme of the Arg-->Orn-->Glu-->GABA pathway; the physiological significance of this pathway is still unclear. With 5-fluoromethylornithine, a selective inactivator of ornithine aminotransferase, a tool is in our hands that allows us to study biochemical and behavioral consequences of elevated tissue ornithine concentrations. Increase of the rate of hepatic urea formation, and of ornithine decarboxylation are the most important changes in vertebrates following inactivation of ornithine aminotransferase. Administration of 5-fluoromethylornithine prevented the accumulation of lethal concentrations of ammonia in brain, and ameliorated pathological consequences of thioacetamide intoxication. Inhibition of ornithine catabolism has, therefore, potentials in the therapy of those hyperammonemic states which are characterized by a conditional deficiency of ornithine. The enhancement of polyamine formation due to elevated ornithine concentrations may allow us to favorably affect tissue regeneration following injury.
Topics: Ammonia; Animals; Brain; Brain Diseases; Humans; Ornithine; Ornithine-Oxo-Acid Transaminase; Polyamines; gamma-Aminobutyric Acid
PubMed: 8272027
DOI: 10.1007/BF00996928