Biomaterial Database

Mechanisms of the inhibition of human erythrocyte pyridoxal kinase by drugs. 1997

P Lainé-Cessac, and A Cailleux, and P Allain

Laboratoire de Pharmacologie Toxicologie, Centre Hospitalier Universitaire, Angers, France.

The aim of this study was to investigate the interaction between drugs chosen for their clinical neurotoxicity or chemical structure and vitamin B6 metabolism. After a preliminary screening of drugs to determine their potential inhibitory effect on erythrocyte nonpurified pyridoxal kinase (PLK) (EC 2.7.1.35), additional investigations, including kinetic studies and detection of chemical reactivity between the inhibiting drugs and pyridoxal (PL) or pyridoxal-5'-phosphate (PLP), using UV-visible spectrophotometry and mass analysis, were carried out to specify the mechanism of PLK inhibition. Depending on the results, the inhibiting drugs were divided into three groups. The first group included theophylline and progabide and inhibited PLK using either PL or pyridoxamine (PM) as substrate and thereby were true inhibitors. Moreover, they did not form covalent complexes with PL or PLP. The second group, which included cycloserine, dopamine, isoniazid, and thiamphenicol glycinate, inhibited PLK using PL, but not PM, as substrate. They were able to react with PL or PLP to form covalent complexes, and kinetic studies suggested that the observed PLK inhibition was due to these formed complexes. A third group, which consisted of levodopa, D-penicillamine, and muzolimine, inhibited PLK using PL, but not PM, as substrate. They formed, with PL or PLP, chemical derivatives that probably had no inhibitory effect on PLK. These results and the clinical consequences of such interactions are discussed and compared with results of previous studies.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D009156	Muzolimine	A pyrazole diuretic with long duration and high capacity of action. It was proposed for kidney failure and hypertension but was withdrawn worldwide because of severe neurological effects.	Bay G 2821,G 2821, Bay
D011730	Pyridoxal	The 4-carboxyaldehyde form of VITAMIN B 6 which is converted to PYRIDOXAL PHOSPHATE which is a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid.
D011731	Pyridoxal Kinase	An enzyme that catalyzes reversibly the phosphorylation of pyridoxal in the presence of ATP with the formation of pyridoxal 5-phosphate and ADP. Pyridoxine, pyridoxamine and various derivatives can also act as acceptors. EC 2.7.1.35.	Pyridoxamine Kinase,Pyridoxine Kinase,Pyridoxal Phosphokinase,Kinase, Pyridoxal,Kinase, Pyridoxamine,Kinase, Pyridoxine,Phosphokinase, Pyridoxal
D004347	Drug Interactions	The action of a drug that may affect the activity, metabolism, or toxicity of another drug.	Drug Interaction,Interaction, Drug,Interactions, Drug
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D004912	Erythrocytes	Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.	Blood Cells, Red,Blood Corpuscles, Red,Red Blood Cells,Red Blood Corpuscles,Blood Cell, Red,Blood Corpuscle, Red,Erythrocyte,Red Blood Cell,Red Blood Corpuscle
D005680	gamma-Aminobutyric Acid	The most common inhibitory neurotransmitter in the central nervous system.	4-Aminobutyric Acid,GABA,4-Aminobutanoic Acid,Aminalon,Aminalone,Gammalon,Lithium GABA,gamma-Aminobutyric Acid, Calcium Salt (2:1),gamma-Aminobutyric Acid, Hydrochloride,gamma-Aminobutyric Acid, Monolithium Salt,gamma-Aminobutyric Acid, Monosodium Salt,gamma-Aminobutyric Acid, Zinc Salt (2:1),4 Aminobutanoic Acid,4 Aminobutyric Acid,Acid, Hydrochloride gamma-Aminobutyric,GABA, Lithium,Hydrochloride gamma-Aminobutyric Acid,gamma Aminobutyric Acid,gamma Aminobutyric Acid, Hydrochloride,gamma Aminobutyric Acid, Monolithium Salt,gamma Aminobutyric Acid, Monosodium Salt
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013056	Spectrophotometry, Ultraviolet	Determination of the spectra of ultraviolet absorption by specific molecules in gases or liquids, for example Cl2, SO2, NO2, CS2, ozone, mercury vapor, and various unsaturated compounds. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)	Ultraviolet Spectrophotometry