Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

5-Aminolevulinic acid (ALA), a heme precursor accumulated during the clinical expression of acute intermittent porphyria, lead poisoning, and tyrosinosis, has been hypothesized to act as an endogenous source of oxyradicals. We now report oxidative effects on brain tissue of rats submitted to ALA treatment. Upon acute treatment (40 mg/kg body weight) increased total nonheme iron in the cortex (20%) was observed. After prolonged ALA administration (40 mg/kg body weight on alternate days during 2 weeks), the following indicators of oxidative stress were found to be significantly increased: CuZnSOD activity (67%) in total brain homogenate, total iron (68%) and ferritin (71%) in the cortex, ferritin in striatum (44%), protein carbonyls in homogenate of cerebral cortex (threefold) and 45Ca2+ uptake by cortical synaptosomes (45%). In addition, synaptic membranes prepared from whole brain assayed with the radioligand 3H-muscimol, revealed increased Kd values (twofold) of the high-affinity GABAergic receptor binding and formation of protein carbonyl groups, thiobarbituric acid reactive products, and conjugated dienes. In vitro, ALA produced similar effects upon the high affinity 3H-muscimol binding. No apparent alteration of either dopaminergic or serotonergic [3H]-ligand binding was observed. These results argue in favor of ALA-triggered oxidative stress in brain accompanied by iron metabolism alterations and GABAergic receptor damage, which may be implicated in the neuropsychiatric manifestations of the aforementioned porphyrias.
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PMID:The prooxidant effect of 5-aminolevulinic acid in the brain tissue of rats: implications in neuropsychiatric manifestations in porphyrias. 872 Aug 99

Highly reactive oxyradicals can be generated in vitro by iron-catalyzed aerobic oxidation of synthetic and naturally occurring substances capable of enolization in aqueous medium. Of biological interest are alpha-hydroxy- and alpha-aminocarbonyls such as carbohydrates, 5-aminolevulinic acid, and aminoacetone which tautomerize to the corresponding enediols and enolamines and yield oxyradicals initiated by electron transfer to dioxygen. Free radicals have been implicated in several normal and pathological processes. We briefly review our hypothesis of an in vivo prooxidant role of 5-aminolevulinic acid (ALA), the heme precursor accumulated in several porphyric disorders (e.g., lead poisoning, acute intermittent porphyria (AIP), tyrosinosis). Accordingly, i) ALA undergoes transition metal-catalyzed oxidation to give O-2, H2O2 and HO.; ii) ALA induces iron release from ferritin, lipid peroxidation of cardiolipin-rich vesicles, single strand breaks in plasmid DNA, and guanosine oxidation in calf thymus DNA; iii) ALA causes Ca(2+)-mediated rat liver mitochondria permeabilization; iv) rats chronically treated with ALA exhibit increased glycolytic metabolism; v) brain extracts of ALA-treated rats reveal increased levels of thiobarbituric acid reactive substances, direct chemiluminescence intensity, carbonyl proteins, ferritin, and "free iron" and gamma-aminobutyric acid-receptor dissociation constant, and vi) patients with AIP and lead-exposed workers present augmented erythrocytic levels of the antioxidant enzymes superoxide dismutase and glutathione peroxidase. These data indicate the involvement of ALA-generated reactive species in the clinical manifestations (neuropathy, mental changes, muscle weakness, hepatoma) shared by the aforementioned inherited and acquired porphyric diseases.
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PMID:Oxidative stress in acute intermittent porphyria and lead poisoning may be triggered by 5-aminolevulinic acid. 907 Mar 73

Amino metabolites with potential prooxidant properties, particularly alpha-aminocarbonyls, are the focus of this review. Among them we emphasize 5-aminolevulinic acid (a heme precursor formed from succinyl-CoA and glycine), aminoacetone (a threonine and glycine metabolite), and hexosamines and hexosimines, formed by Schiff condensation of hexoses with basic amino acid residues of proteins. All these metabolites were shown, in vitro, to undergo enolization and subsequent aerobic oxidation, yielding oxyradicals and highly cyto- and genotoxic alpha-oxoaldehydes. Their metabolic roles in health and disease are examined here and compared in humans and experimental animals, including rats, quail, and octopus. In the past two decades, we have concentrated on two endogenous alpha-aminoketones: (i) 5-aminolevulinic acid (ALA), accumulated in acquired (e.g., lead poisoning) and inborn (e.g., intermittent acute porphyria) porphyric disorders, and (ii) aminoacetone (AA), putatively overproduced in diabetes mellitus and cri-du-chat syndrome. ALA and AA have been implicated as contributing sources of oxyradicals and oxidative stress in these diseases. The end product of ALA oxidation, 4,5-dioxovaleric acid (DOVA), is able to alkylate DNA guanine moieties, promote protein cross-linking, and damage GABAergic receptors of rat brain synaptosome preparations. In turn, methylglyoxal (MG), the end product of AA oxidation, is also highly cytotoxic and able to release iron from ferritin and copper from ceruloplasmin, and to aggregate proteins. This review covers chemical and biochemical aspects of these alpha-aminoketones and their putative roles in the oxidative stress associated with porphyrias, tyrosinosis, diabetes, and cri-du-chat. In addition, we comment briefly on a side prooxidant behaviour of hexosamines, that are known to constitute building blocks of several glycoproteins and to be involved in Schiff base-mediated enzymatic reactions.
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PMID:The dual face of endogenous alpha-aminoketones: pro-oxidizing metabolic weapons. 1692 Apr 3