Search PubMed⌕ Search

Biomedical subjects

A Meister

Publications and source records attributed to A Meister.

At least 343 records · Page 19Linked to original sources
PubMed1971

Reversible dissociation of carbamyl phosphate synthetase into a regulated synthesis subunit and a subunit required for glutamine utilization.

Carbamyl phosphate synthetase (from Escherichia coli) consists of a 7.3S protomeric unit that contains one heavy polypeptide chain (molecular weight about 130,000) and one light chain (molecular weight about 42,000). The heavy and light chains were separated by gel filtration in the presence of 1 M potassium thiocyanate. In contrast to the native enzyme and the reconstituted enzyme (prepared by mixing the separated heavy and light chains), the heavy chain does not catalyze glutamine-dependent carbamyl phosphate synthesis, although it does catalyze the synthesis of carbamyl phosphate from ammonia. The heavy chain also catalyzes two of the partial reactions catalyzed by the intact enzyme; i.e., the bicarbonate-dependent cleavage of ATP and the synthesis of ATP from ADP and carbamyl phosphate. Both positive (ammonia, ornithine, IMP) and negative (UMP) allosteric regulatory sites are located on the heavy chain. The only catalytic activity exhibited by the light chain is the hydrolysis of glutamine. A model is presented according to which glutamine binds to the light chain, which is followed by release of nitrogen from the amide group for use by the heavy chain. The findings suggest that glutamine-dependent carbamyl phosphate synthetase (and perhaps other glutamine amidotransferases) arose in the course of evolution by a combination of a primitive ammonia-dependent synthetic enzyme and a glutaminase; this combination may have been associated with a change from ammonia to glutamine as the principal source of nitrogen.

Adenosine Diphosphate↗
PubMed1971

Enzymatic conversion of 5-oxo-L-proline (L-pyrrolidone carboxylate) to L-glutamate coupled with cleavage of adenosine triphosphate to adenosine diphosphate, a reaction in the -glutamyl cycle.

A new enzyme, 5-oxoprolinase, was found in rat kidney and in several other tissues; it catalyzes the conversion of 5-oxo-L-proline (L-5-oxo-pyrrolidine-2-carboxylic acid, L-2-pyrrolidone-5-carboxylic acid, L-pyroglutamic acid) to L-glutamic acid, with concomitant stoichiometric cleavage of ATP to ADP and orthophosphate. The reaction catalyzed by 5-oxoprolinase, in which 5-oxoproline formed from gamma-glutamyl amino acids by the action of gamma-glutamylcyclotransferase is converted to glutamate, appears to function in the gamma-glutamyl cycle. 5-Oxoprolinase requires Mg(++) (or Mn(++)) and K(+) (or NH(4) (+)) for activity. The equilibrium is markedly in favor of glutamate formation at pH 7.8.

Adenine Nucleotides↗
PubMed1971

Regulation of rat liver glutamine synthetase: activation by alpha-ketoglutarate and inhibition by glycine, alanine, and carbamyl phosphate.

Rat liver glutamine synthetase (s(20,w) 15.0 S; MW about 352,000) resembles ovine brain glutamine synthetase in that it (a) has 8 subunits, (b) acts on both L- and D-glutamate and certain glutamate analogs (e.g., beta-glutamate, cis-cycloglutamate, and alpha-methyl-L-glutamate), and (c) is irreversibly inhibited by L-methionine-S-sulfoximine. The liver enzyme (but not the brain enzyme) is (a) markedly activated by alpha-ketoglutarate and less so by citrate, and (b) inhibited noncumulatively by glycine and alanine, in the presence of Mn(++) but not Mg(++); inhibition increases with increasing concentrations of glutamate. These regulatory phenomena seem to be correlated with metabolically related enzymes, e.g., glutamine transaminase. Both liver and brain glutamine synthetases are inhibited by carbamyl phosphate (with Mn(++) but not with Mg(++)), which provides a means for controlling glutamine for pyrimidine biosynthesis. Addition of Mn(++) to the Mg(++)-synthetase system, even at Mg(++): Mn(++) ratios of 1000, markedly inhibits synthesis by both brain and liver enzymes. This finding, and the fact that Mn(++) promotes sensitivity to the negative effectors, indicates that Mn(++) plays a central role in the regulation of glutamine synthetase. Properties of the glutamine synthetases that have been isolated from mammalian, plant, and bacterial cells are compared. They are similar with respect to subunit size, substrate specificity, inhibition by methionine sulfoximine, and Mn(++)-sensitive inhibition by glycine, alanine, and carbamyl phosphate, but differ in certain other regulatory phenomena and in subunit structure.

Alanine↗
PubMed1971

Decrease of the 3,4-dihydroxyphenylalanine (DOPA) decarboxylase activities in human erythrocytes and mouse tissues after administration of DOPA.

Human erythrocytes have been found to contain appreciable amounts of DOPA decarboxylase (EC 4.1.1.26) activity. The enzyme activity in erythrocytes from patients with Parkinson's disease who were treated with DOPA was significantly lower than that of untreated patients and of normal individuals. Administration of the drug to mice led to a marked decrease of DOPA decarboxylase in liver and kidney, but not of the brain enzyme. The findings thus indicate that administration of DOPA leads to a decrease in peripheral DOPA decarboxylase, an effect that is expected to be of benefit in DOPA therapy of patients with Parkinson's disease. Peripheral DOPA decarboxylase concentration also decreases in mice after short periods of fasting; the findings suggest that the peripheral enzyme activities may be affected by various nutritional and perhaps hormonal influences, which may be partially responsible for the observed fluctuations in the motor abilities of Parkinsonian patients receiving constant doses of the drug. Study of DOPA decarboxylase activity in erythrocytes may be useful in following changes in patients receiving DOPA therapy and may also be of general interest and value in investigations of catecholamine metabolism in man.

Age Factors↗
PubMed1970

Identification of L-methionine-S-sulfoximine as the convulsant isomer of methionine sulfoximine.

The convulsant agent methionine sulfoximine inhibits brain glutamine synthetase irreversibly and the inhibitor becomes bound to the active site of the enzyme as methionine sulfoximine phosphate. Only one of the four isomers of methionine sulfoximine, L-methionine-S-sulfoximine, inhibits glutamine synthetase. In the present work, D-methionine-SR-sulfoximine, and highly purified preparations of L-methionine-S-sulfoximine and L-methionine-R-sulfoximine were tested in mice for convulsant activity; only L-methionine-S-sulfoximine produced convulsions. The finding that only one of the four optical isomers of methionine sulfoximine induces convulsions, and that only this same isomer inhibits glutamine synthetase, lends support to the conclusion that these two effects of methionine sulfoximine are closely connected.

Animals↗
PubMed1970

The gamma-glutamyl cycle: a possible transport system for amino acids.

Evidence is presented that rat kidney contains enzymes that catalyze the synthesis and utilization of glutathione; these reactions, which involve the uptake and release of amino acids from gamma-glutamyl linkage, constitute a cyclical process which is termed "the gamma-glutamyl cycle." The gamma-glutamyl cycle has properties that fulfill the requirements of an amino acid transport system. Thus, gamma-glutamyl transpeptidase may function in translocation and gamma-glutamylcysteine synthetase and glutathione synthetase may catalyze energy-requiring "recovery" steps in transport. These and other considerations suggest that glutathione serves a carrier function in amino acid transport.

Amino Acids↗