Biomaterial Database

Glutamate decarboxylase inhibition and vitamin B6 metabolism in brain of cirrhotic rats chronically treated with carbon tetrachloride. 1988

M Díaz-Muñoz, and R Tapia

Departamento de Neurociencias, Instituto de Fisiología Celular, Univerisdad Nacional Autónoma de México, D.F.

In a previous work we found that the activity of glutamate decarboxylase (GAD), the enzyme responsible for the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), is decreased in comatose cirrhotic rats after chronic treatment with CCl4. In the present report we studied the participation of pyridoxal phosphate in the inhibition of GAD, as well as the concentration of this coenzyme and the activity of its synthesizing enzyme, pyridoxal kinase, in the brain of the cirrhotic rats. Furthermore, cirrhotic animals were treated with three inhibitors of GAD, and the effects of such treatment were compared to those of ammonium. Liver failure resulted in a 25% inhibition of GAD activity when measured in the absence of added pyridoxal phosphate. Treatment with the GAD inhibitors thiosemicarbazide or 3-mercaptopropionic acid enhanced this inhibition and produced convulsions at a dose that had no behavioral effects in control rats. Treatment with ammonia resulted in a comatose state and in a 25-40% inhibition of GAD. Both pyridoxal kinase activity and pyridoxal phosphate levels were found to be decreased by 15-20% in the brain of the cirrhotic rats. We concluded that chronic liver failure results in a decreased pyridoxal phosphate and GABA synthesis in brain, with a consequent diminished efficiency of GABAergic neurotransmission; these effects are probably related to the manifestations of neuronal hyperexcitability that are frequently seen in human hepatic encephalopathy.

UI	MeSH Term	Description	Entries
D008106	Liver Cirrhosis, Experimental	Experimentally induced chronic injuries to the parenchymal cells in the liver to achieve a model for LIVER CIRRHOSIS.	Hepatic Cirrhosis, Experimental,Cirrhoses, Experimental Liver,Cirrhosis, Experimental Liver,Experimental Liver Cirrhoses,Experimental Liver Cirrhosis,Liver Cirrhoses, Experimental,Experimental Hepatic Cirrhosis
D008297	Male		Males
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
D011732	Pyridoxal Phosphate	This is the active form of VITAMIN B 6 serving as a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. During transamination of amino acids, pyridoxal phosphate is transiently converted into pyridoxamine phosphate (PYRIDOXAMINE).	Pyridoxal 5-Phosphate,Pyridoxal-P,Phosphate, Pyridoxal,Pyridoxal 5 Phosphate,Pyridoxal P
D011736	Pyridoxine	The 4-methanol 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. Although pyridoxine and Vitamin B 6 are still frequently used as synonyms, especially by medical researchers, this practice is erroneous and sometimes misleading (EE Snell; Ann NY Acad Sci, vol 585 pg 1, 1990).	Pyridoxin,Pyridoxine Hydrochloride,Pyridoxol,Pyridoxol Hydrochloride,Rodex
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D002251	Carbon Tetrachloride	A solvent for oils, fats, lacquers, varnishes, rubber waxes, and resins, and a starting material in the manufacturing of organic compounds. Poisoning by inhalation, ingestion or skin absorption is possible and may be fatal. (Merck Index, 11th ed)	Tetrachloromethane,Tetrachloride, Carbon
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
D005968	Glutamate Decarboxylase	A pyridoxal-phosphate protein that catalyzes the alpha-decarboxylation of L-glutamic acid to form gamma-aminobutyric acid and carbon dioxide. The enzyme is found in bacteria and in invertebrate and vertebrate nervous systems. It is the rate-limiting enzyme in determining GAMMA-AMINOBUTYRIC ACID levels in normal nervous tissues. The brain enzyme also acts on L-cysteate, L-cysteine sulfinate, and L-aspartate. EC 4.1.1.15.	Glutamate Carboxy-Lyase,Glutamic Acid Decarboxylase,Acid Decarboxylase, Glutamic,Carboxy-Lyase, Glutamate,Decarboxylase, Glutamate,Decarboxylase, Glutamic Acid,Glutamate Carboxy Lyase
D000085	Acetates	Derivatives of ACETIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxymethane structure.	Acetate,Acetic Acid Esters,Acetic Acids,Acids, Acetic,Esters, Acetic Acid