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.