Protein modification by methylglyoxal: chemical nature and synthetic mechanism of a major fluorescent adduct.

The nonenzymatic Maillard reaction of proteins, initiated by the addition of sugars and other aldehydes and ketones, is thought to be an important mechanism in aging and the pathogenesis of diabetic complications. The alpha-dicarbonyl compounds are considered to be key intermediates in this reaction. Methylglyoxal (MG) (pyruvaldehyde), a physiological alpha-dicarbonyl compound, has been shown to modify proteins both in vitro and in vivo.

Protein cross-linking by the Maillard reaction. Isolation, characterization, and in vivo detection of a lysine-lysine cross-link derived from methylglyoxal.

The Maillard reaction, initiated by nonenzymatic glycosylation of amino groups on proteins by reducing sugars, has been studied for its potential role in aging and the complications of diabetes. One of the major consequences of the advanced Maillard reaction in proteins is the formation of covalently cross-linked aggregates. The chemical nature of the cross-linking structures is largely unknown.

Heat treatment of Corynebacterium ammoniagenes leads to aeration dependent accumulation of 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate.

2-C-methyl-D-erythritol-2,4-cyclopyrophosphate (MEC) identified as a new bacterial oxidative stress substance (Ostrovsky D. et al. (1993) Biochem.

1H and 13C NMR study of the molecular interaction mechanism between chloramphenicol and human serum albumin.

Molecular mechanism of the interaction between human serum albumin and cloramphenicol was studied by 1H and 13C NMR-spectroscopy. It was found that the main role belongs to [formula: see text] groups of chloramphenicol. A schematic model of the complex-formation between serum albumin and chloramphenicol was proposed.

Bacterial oxidative stress substance spontaneously recyclizes to form 2-methylbutane-1,2,3,4-tetraol-1,2-cyclophospho-4-phosphate.

The cells of Corynebacterium (Brevibacterium) ammonia-genes cultivated in a medium supplemented with diquat or benzylviologen accumulate 2-methylbutane-1,2,3,4-tetraol-2,4- cyclopyrophosphate as revealed by 31P-NMR spectroscopy. On heating at 120 degrees C for 30 min the cells still maintain a substantial portion of this compound and acquire new cyclic phosphates characterized by 31P-NMR chemical shifts of +17.3 and +20 p.

Bacteria and pesticides: a new aspect of interaction--involvement of a new biofactor.

Positively charged hydrophobic pesticides of the dipyridyl family [diquat, paraquat, benzylviologen (BV++), etc.] were shown to provoke accumulation of 2-methylbutane-1,2,3,4-tetraol-2,4- cyclopyrophosphate in the cells Corynebacterium (Brevibacterium) ammoniagenes while neutral dipyridyls were not. Hydrophobicity was also an important factor in this phenomenon.

The ability of bacteria to synthesize a new cyclopyrophosphate correlates with their tolerance to redox-cycling drugs: on a crossroad of chemotherapy, environmental toxicology and immunobiochemical problems.

Many redox-cyclers were recently shown to induce, in some bacterial species, large-scale biosynthesis of a new 2-methylbutan-1,2,3,4-tetraol-2,4-cyclopyrophosphate believed to be involved in anti-stress reactions. In the present study Mycobacterium smegmatis, Micrococcus luteus and Brevibacterium ammoniagenes were shown to begin synthesis of the new cyclopyrophosphate when cultivated in a medium containing furacilin or furadonin (widely used nitrofuran antibacterial drugs) and to maintain close to normal growth rates, whereas Staphylococcus aureus, Bacillus subtilis and Escherichia coli were inhibited by the drugs and were unable to synthesize the cyclopyrophosphate compound. Preferential binding of Mg2+ and Cd2+ with one or other phosphoryl groups of the cyclopyrophosphate, which was indicated by selective changes of 31P-NMR chemical shifts and intramolecular hydrogen bonding, is suggested as a reason for this selectivity.

Synthesis of a new organic pyrophosphate in large quantities is induced in some bacteria by oxidative stress.

Brevibacterium ammoniagenes and Micrococcus luteus were shown to synthesize up to 50 mM of a novel substance, 2-methylbutan-1,2,3,4-tetraol 2,4-cyclopyrophosphate, in response to oxidative stress created by benzyl viologen and other redox mediators under aerobic conditions. The substance, which represents greater than 50% of the extractable phosphorus, is suggested to play a role as a bacterial antistressor and is thought to be a product of condensation of two molecules of phosphoenolpyruvate whose accumulation is prompted by conversion of intracellular NADPH into an oxidized form.

A new cyclopyrophosphate as a bacterial antistressor?

In a number of bacteria an unusual glycosyl pyrophosphate (31P NMR signal chemical shift at about -15 ppm) was detected when the cells were subjected to oxidative stress. This substance from Brevibacterium ammoniagenes has now been identified as 2-methyl-butan-1,2,3,4,-tetraol-2,4-cyclopyrophosphate, which is accumulated in the cell under certain conditions in concentrations of of about 50 mM. It is now suggested that this compound is the long sought after bacterial antistressor.