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G Srivastava

Publications and source records attributed to G Srivastava.

At least 145 records · Page 8Linked to original sources
PubMed1986

Control of 5-aminolevulinate synthase in animals.

The proposed mechanism by which hepatic ALV-synthase mitochondrial levels are regulated is outlined in Fig. 2. ALV-synthase catalyzes the first and rate-limiting step in the heme pathway and is normally present in low amounts. A cytosolic, regulatory free heme pool tightly controls the amount of ALV-synthase in two ways. In the primary mechanism of regulation, heme is proposed to inhibit the synthesis of ALV-synthase mRNA. Most likely this would be mediated through the action of specific heme-binding protein(s) which recognize regulatory control regions of the ALV-synthase gene. Gene activity therefore is significantly repressed most of the time. When there is an increased demand for heme by newly synthesized cellular hemoproteins, the free heme pool is reduced, leading to a derepression of ALV-synthase mRNA synthesis. Once the need for increased heme synthesis is satisfied, inhibitory heme levels build up again. When drugs such as phenobarbital are administered to animals, there is a rapid induction in the liver of both cytochrome P-450 and ALV-synthase. It is proposed that the heme pool governing ALV-synthase levels is lowered by the increased heme demand due to cytochrome P-450 apoprotein formation. The primary event in the drug induction of ALV-synthase is therefore the increased synthesis of cytochrome P-450 apoprotein. However, the mechanism by which this occurs is unknown, although drugs do increase the synthesis of mRNA for cytochrome P-450 (Fig. 2). (There is evidence that for the aromatic hydrocarbons a specific cytosolic receptor exists.) In the acute hepatic porphyria diseases, uncontrolled synthesis of hepatic ALV-synthase occurs. The various forms are characterized by reduced levels of one of the heme pathway enzymes other than ALV-synthase. Attacks of the disease are commonly precipitated by drugs which induce cytochrome P-450, and the uncontrolled accumulation of ALV-synthase which accompanies these attacks results from the combined action of the block in the heme pathway and the increased cytochrome P-450 levels. A major challenge which now exists is to understand at the molecular level how the genes for ALV-synthase and cytochrome P-450 are regulated in the liver and other tissues.(ABSTRACT TRUNCATED AT 400 WORDS)

5-Aminolevulinate Synthetase↗
PubMed1986

Exfoliative dermatitis. A prospective study of 80 patients.

A prospective study in 80 exfoliative dermatitis patients over a period of 5 years establishes 41.9 years as its mean age at onset. The disease affected both males and females, with a preponderance of the former. The clinical features were identical, irrespective of the etiology. The onset of the disease was usually insidious except in staphylococcal scalled skin syndrome and drug-induced erythroderma, where it was abrupt and florid. Microcytic hypochromic anemia, elevated erythrocyte sedimentation rate, eosinophilia, low serum proteins and electrolytes were salient laboratory features. Histopathology was largely unrewarding; only in 12 patients, a good clinicohistologic correlation was present. Preexisting dermatoses, namely psoriasis, air-borne contact dermatitis, phytophotodermatitis, photosensitive and seborrheic dermatitis, and other dermatoses constituted the major etiology. Antituberculous drugs were responsible for a substantial proportion of drug-induced erythroderma. No lymphomas were found. This study outlines that some salient features of exfoliative dermatitis may show geographic variations.

Adult↗
PubMed1985

Complete nucleotide sequence of hepatic 5-aminolaevulinate synthase precursor.

Chick embryo liver mitochondrial matrix protein, 5-aminolaevulinate synthase, is synthesised initially as a larger cytosolic precursor. In this report we present the complete nucleotide sequence of a cDNA clone coding for the precursor together with corresponding confirmatory amino acid sequence of peptides derived from purified mature mitochondrial enzyme. The deduced amino acid sequence shows that the precursor consists of mature enzyme of 579 amino acids and an N-terminal extension of 56 amino acids. The latter presequence is highly basic in character as found with other mitochondrial preproteins.

5-Aminolevulinate Synthetase↗
PubMed1985

Histoid leprosy.

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Aged↗
PubMed1984

Electron microscopic studies on liver 5-aminolaevulinate synthase.

The structure of chick embryo liver 5-aminolaevulinate synthase has been examined by electron microscopic studies using negative staining. From the different projections of the enzyme particles observed in electron micrographs, a model for the enzyme molecule has been proposed. In this model, an enzyme molecule consists of two curved and identical subunits associated in opposite polarities. From the dimensions of an enzyme molecule subunit measured from electron micrographs, the relative molecular mass of each subunit is estimated to be 70 000.

5-Aminolevulinate Synthetase↗
PubMed1984

Molecular cloning of hepatic 5-aminolevulinate synthase.

Hepatic 5-aminolevulinate synthase was induced in chick embryos by administration of the porphyrinogenic drugs 2-allyl-2-isopropylacetamide and 3,5-diethoxycarbonyl-1,4-dihydrocollidine. A cDNA library was constructed from drug-induced liver mRNA and clones containing sequences coding for 5-aminolevulinate synthase were identified by hybrid-selected translation. The identity of these clones was confirmed by comparing DNA sequence data with the amino acid sequence of peptides from purified 5-aminolevulinate synthase. From Northern blot analysis the size of the mRNA for 5-aminolevulinate synthase was estimated to be 2800 base pairs, approximately 600 base pairs more than that required to code for the primary translation product of relative molecular mass 74000.

5-Aminolevulinate Synthetase↗
PubMed1984

Effect of lead ions on chick-embryo liver mitochondrial delta-aminolaevulinate synthase.

Pb2+ activated native chick-embryo liver mitochondrial delta-aminoaevulinate synthase (EC 2.3.1.37). This result contradicted with the inhibitory effect observed by earlier workers who used degraded enzyme preparations. Enzyme activation was biphasic. An initial activation phase was observed with Pb2+ concentrations up to 200 microM, and a secondary phase with concentrations from 200 microM to at least 2mM. Maximum primary activation was 2.5-fold at 200 microM-Pb2+, with a further 2-fold activation observed at 2mM-Pb2+. Primary activation was not affected by a 10-fold molar excess of dithioerythritol, but the secondary activation was abolished by dithioerythritol. Secondary-phase activation was lost upon increasing time of incubation of the enzyme with Pb2+. The implications of these findings are discussed with reference to lead poisoning and the mechanism of delta-aminolaevulinate synthase.

5-Aminolevulinate Synthetase↗
PubMed1984

Interaction of substance P with dispersed pancreatic acinar cells from the guinea pig. Relationships between structure, binding and biological activity.

Binding of 125I-[Tyr8]-SP to isolated pancreatic acinar cells was inhibited in a concentration-dependent way by SP, [Tyr8]-SP and longer C-terminal fragments of SP. SP6-11 was the shortest sequence to bind significantly to SP-receptors as well as to stimulate amylase release from dispersed pancreatic acini. SP7-11 and shorter fragments did not inhibit binding of 125I-[Tyr8]-SP and did not stimulate secretion of amylase significantly. SP augmented the stimulatory effect of cholecystokinin on amylase release. Two SP-antagonists, [D-Pro2, D-Trp7,9]-SP and [D-Pro2,4, D-Lys3, D-Gln5,6, D-Trp7,9]-SP inhibited binding of 125I-[Tyr8]-SP in a concentration dependent manner and tended at a high concentration to reduce release of amylase evoked by submaximal concentrations of SP.

Amylases↗
PubMed1983

Hemin inhibits transfer of pre-delta-aminolevulinate synthase into chick embryo liver mitochondria.

Pulse labelling studies in chick embryo livers show that hemin prevents the transfer of drug induced pre-delta-aminolevulinate synthase from the cytosol into the mitochondria, leading to an accumulation of precursor in the cytosol. No effect of hemin was observed on the transfer of pre-pyruvate carboxylase into mitochondria. These results eliminated a general toxic effect of hemin on mitochondrial import of proteins and are consistent with the view that hemin specifically inhibits the transfer of ALA synthase.

5-Aminolevulinate Synthetase↗
PubMed1983

Evidence that 2-allyl-2-isopropylacetamide, phenobarbital and 3,5-diethoxycarbonyl-1,4-dihydrocollidine induce the same cytochrome P450 mRNA in chick embryo liver.

The induction of cytochrome P450 in chick embryo liver has been studied using three different porphyrinogenic drugs, 2-allyl-2-isopropylacetamide, 3,5-diethoxycarbonyl-1,4-dihydrocollidine and phenobarbital. Pulse-labelling studies have shown that for each drug the cytochrome P450 synthesized either in ovo or in a wheat germ translation system reacted immunologically with antibody raised against the purified 2-allyl-2-isopropylacetamide-induced enzyme (Mr = 50000). To investigate whether this is due to the three drugs inducing the same protein or different proteins with common immunological determinants, nucleic acid hybridization studies have been carried out using a recently characterised 2-allyl-2-isopropylacetamide-induced cytochrome P450 cloned cDNA probe [Brooker, J. D. et al. (1982) Eur. J. Biochem. 129, 325-333]. It has been shown that the mRNA induced by each drug hybridizes with this probe and all are of similar size. The melting profile of the mRNA . cDNA hybrids indicates that the mRNAs induced by the three drugs have at least 98% homology with the cDNA probe. Restriction endonuclease digestions of total chick embryo genomal DNA and a chick cytochrome P450 genomal clone indicates that the cytochrome P450 gene homologous with the cDNA probe is represented in the genome only once. These results strongly suggest that the three drugs cause increased levels of the same cytochrome P450 mRNA, possibly due to enhanced expression of the same gene. Results are also presented which show that other cytochrome-P450-inducing drugs, 3-methylcholanthrene, beta-naphthoflavone or pregnenolone-16 alpha-carbonitrile do not increase the level of the 2-allyl-2-isopropylacetamide-inducible mRNA but rather reduce it to a level which was lower than that of the untreated controls.

Acetamides↗
PubMed1983

Evidence for a cytosolic precursor of chick embryo liver mitochondrial delta-aminolevulinate synthase.

Following the recent demonstration [Borthwick, I.A., Srivastava, G., Brooker, J.D., May, B.K. and Elliott, W.H. (1982) Eur. J. Biochem. in press] that chick embryo liver mitochondrial delta-aminolevulinate synthase has a minimum molecular weight of 68,000 (rather than the hitherto accepted value of 49,000), we have shown that the primary translation product of delta-aminolevulinate synthase mRNA is a protein of molecular weight 74,000. This protein has for the first time been shown to occur in the cytosol fraction of drug-treated chick embryo livers. This form does not occur in mitochondria nor does the smaller mitochondrial form occur in the cytosol. It is concluded that the 74,000 molecular weight protein is a precursor which is processed during transport into the mitochondria. In vivo labelling experiments are consistent with this conclusion.

5-Aminolevulinate Synthetase↗
PubMed1983

Purification of 5-aminolaevulinate synthase from liver mitochondria of chick embryo.

5-Aminolaevulinate synthase from chick-embryo liver mitochondria has, for the first time, been purified to homogeneity in its native non-degraded form by molecular sieve chromatography, chromatofocusing and affinity chromatography. The enzyme has a minimum molecular weight of 68000 as determined by sodium dodecylsulphate/polyacrylamide gel electrophoresis and a specific activity of 35000 units/mg of protein. This result conflicts with the previous report of Whiting, M.J. and Granick, G. [(1976) J. Biol. Chem. 251, 1340-1346] that the chick embryo enzyme has a molecular weight of 49000. We show here that the purified form can be degraded proteolytically to a smaller form of molecular weight around 50000 while retaining full enzymatic activity. It seem evident, therefore, that the enzyme isolated by Whiting & Granick (1976) was degraded. We have further established by pulse-labelling studies and immunoprecipitation that the enzyme isolated by our new and rapid procedure has the same minimum molecular weight as that which exists in vivo.

5-Aminolevulinate Synthetase↗