scholarly journals Developmental and metabolic regulation of the Drosophila melanogaster 3-hydroxy-3-methylglutaryl coenzyme A reductase.

1988 ◽  
Vol 8 (7) ◽  
pp. 2713-2721 ◽  
Author(s):  
F B Gertler ◽  
C Y Chiu ◽  
L Richter-Mann ◽  
D J Chin
Keyword(s):  
Drosophila Melanogaster ◽  
Metabolic Regulation ◽  
Coenzyme A ◽  
Terminal Region ◽  
Cdna Clones ◽  
Posttranslational Regulation ◽  
Hmg Coa Reductase ◽  
Reading Frame ◽  
Reductase Gene ◽  
Coa Reductase

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase in Drosophila melanogaster synthesizes mevalonate for the production of nonsterol isoprenoids, which are essential for growth and differentiation. To understand the regulation and developmental role of HMG CoA reductase, we cloned the D. melanogaster HMG CoA reductase gene. The nucleotide sequence of the Drosophila HMG CoA reductase was determined from genomic and cDNA clones. A 2,748-base-pair open reading frame encoded a polypeptide of 916 amino acids (Mr, 98,165) that was similar to the hamster HMG CoA reductase. The C-terminal region had 56% identical residues and the N-terminal region had 7 potential transmembrane domains with 32 to 60% identical residues. In hamster HMG CoA reductase, the membrane regions were essential for posttranslational regulation. Since the Drosophila enzyme is not regulated by sterols, the strong N-terminal similarity was surprising. Two HMG CoA reductase mRNA transcripts, approximately 3.2 and 4 kilobases, were differentially expressed throughout Drosophila development. Mevalonate-fed Schneider cells showed a parallel reduction of both enzyme activity and abundance of the 4-kilobase mRNA transcript.

Developmental and metabolic regulation of the Drosophila melanogaster 3-hydroxy-3-methylglutaryl coenzyme A reductase

1988 ◽  
Vol 8 (7) ◽  
pp. 2713-2721
Author(s):  
F B Gertler ◽  
C Y Chiu ◽  
L Richter-Mann ◽  
D J Chin
Keyword(s):  
Drosophila Melanogaster ◽  
Metabolic Regulation ◽  
Coenzyme A ◽  
Terminal Region ◽  
Cdna Clones ◽  
Posttranslational Regulation ◽  
Hmg Coa Reductase ◽  
Reading Frame ◽  
Reductase Gene ◽  
Coa Reductase

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase in Drosophila melanogaster synthesizes mevalonate for the production of nonsterol isoprenoids, which are essential for growth and differentiation. To understand the regulation and developmental role of HMG CoA reductase, we cloned the D. melanogaster HMG CoA reductase gene. The nucleotide sequence of the Drosophila HMG CoA reductase was determined from genomic and cDNA clones. A 2,748-base-pair open reading frame encoded a polypeptide of 916 amino acids (Mr, 98,165) that was similar to the hamster HMG CoA reductase. The C-terminal region had 56% identical residues and the N-terminal region had 7 potential transmembrane domains with 32 to 60% identical residues. In hamster HMG CoA reductase, the membrane regions were essential for posttranslational regulation. Since the Drosophila enzyme is not regulated by sterols, the strong N-terminal similarity was surprising. Two HMG CoA reductase mRNA transcripts, approximately 3.2 and 4 kilobases, were differentially expressed throughout Drosophila development. Mevalonate-fed Schneider cells showed a parallel reduction of both enzyme activity and abundance of the 4-kilobase mRNA transcript.

scholarly journals The Promoter of the Rat 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Gene Contains a Tissue-Specific Estrogen-Responsive Region

1999 ◽  
Vol 13 (8) ◽  
pp. 1225-1236 ◽  
Author(s):  
Luciano Di Croce ◽  
Guillermo P. Vicent ◽  
Adali Pecci ◽  
Giovannella Bruscalupi ◽  
Anna Trentalance ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Cell Lines ◽  
Coenzyme A ◽  
Cholesterol Metabolism ◽  
Hmg Coa Reductase ◽  
Tissue Specific ◽  
Reductase Gene ◽  
Responsive Element ◽  
Coa Reductase ◽  
Mcf 7

Abstract The isoprenoid metabolic pathway is mainly regulated at the level of conversion of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) to mevalonate, catalyzed by HMG CoA reductase. As estrogens are known to influence cholesterol metabolism, we have explored the potential regulation of the HMG CoA reductase gene promoter by estrogens. The promoter contains an estrogen-responsive element-like sequence at position −93 (termed Red-ERE), which differs from the ERE consensus by one mismatch in each half of the palindrome. A Red-ERE oligonucleotide specifically bound estrogen receptor in vitro and conferred receptor-dependent estrogen responsiveness to a heterologous promoter in all cell lines tested. However, expression of a reporter driven by the rat HMG CoA reductase promoter was induced by estrogen treatment after transient transfection into the breast cancer cell line MCF-7 cells but not in hepatic cell lines expressing estrogen receptor. Estrogen induction in MCF-7 cells was dependent on the Red-ERE and was strongly inhibited by the antiestrogen ICI 164,384. A functional cAMP-responsive element is located immediately upstream of the Red-ERE, but cAMP and estrogens inhibit each other in terms of transactivation of the promoter. Similarly, induction by estrogens was inhibited by micromolar concentrations of cholesterol, likely acting via changes in occupancy of the sterol-responsive element located 70 bp upstream of the Red-ERE. Thus, within its natural context, Red-ERE is able to mediate hormonal regulation of the HMG CoA reductase gene in tissues that respond to estrogens with enhanced cell proliferation, while it is not operative in liver cells. We postulate that this tissue-specific regulation of HMG CoA reductase by estrogens could partially explain the protective effect of estrogens against heart disease.

Structural and functional conservation between yeast and human 3-hydroxy-3-methylglutaryl coenzyme A reductases, the rate-limiting enzyme of sterol biosynthesis

1988 ◽  
Vol 8 (9) ◽  
pp. 3797-3808
Author(s):  
M E Basson ◽  
M Thorsness ◽  
J Finer-Moore ◽  
R M Stroud ◽  
J Rine
Keyword(s):  
Coenzyme A ◽  
Sterol Biosynthesis ◽  
New Drugs ◽  
Yeast Cells ◽  
Cdna Clones ◽  
Hmg Coa Reductase ◽  
Functional Conservation ◽  
Mammalian Enzyme ◽  
Coa Reductase ◽  
Rate Limiting

The pathway of sterol biosynthesis is highly conserved in all eucaryotic cells. We demonstrated structural and functional conservation of the rate-limiting enzyme of the mammalian pathway, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoA reductase), between the yeast Saccharomyces cerevisiae and humans. The amino acid sequence of the two yeast HMG-CoA reductase isozymes was deduced from DNA sequence analysis of the HMG1 and HMG2 genes. Extensive sequence similarity existed between the region of the mammalian enzyme encoding the active site and the corresponding region of the two yeast isozymes. Moreover, each of the yeast isozymes, like the mammalian enzyme, contained seven potential membrane-spanning domains in the NH2-terminal region of the protein. Expression of cDNA clones encoding either hamster or human HMG-CoA reductase rescued the viability of hmg1 hmg2 yeast cells lacking this enzyme. Thus, mammalian HMG-CoA reductase can provide sufficient catalytic function to replace both yeast isozymes in vivo. The availability of yeast cells whose growth depends on human HMG-CoA reductase may provide a microbial screen to identify new drugs that can modulate cholesterol biosynthesis.

Design and Synthesis of Seco-oxysterol Analogs as Potential Inhibitors of 3-Hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) Reductase Gene Transcription

1994 ◽  
Vol 37 (15) ◽  
pp. 2343-2351 ◽  
Author(s):  
Scott D. Larsen ◽  
Charles H. Spilman ◽  
Yoshi Yagi ◽  
Dac M. Dinh ◽  
Karen L. Hart ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Coenzyme A ◽  
Hmg Coa Reductase ◽  
Design And Synthesis ◽  
Reductase Gene ◽  
Coa Reductase ◽  
Potential Inhibitors

scholarly journals Structural and functional conservation between yeast and human 3-hydroxy-3-methylglutaryl coenzyme A reductases, the rate-limiting enzyme of sterol biosynthesis.

1988 ◽  
Vol 8 (9) ◽  
pp. 3797-3808 ◽  
Author(s):  
M E Basson ◽  
M Thorsness ◽  
J Finer-Moore ◽  
R M Stroud ◽  
J Rine
Keyword(s):  
Coenzyme A ◽  
Sterol Biosynthesis ◽  
New Drugs ◽  
Yeast Cells ◽  
Cdna Clones ◽  
Hmg Coa Reductase ◽  
Functional Conservation ◽  
Mammalian Enzyme ◽  
Coa Reductase ◽  
Rate Limiting

The pathway of sterol biosynthesis is highly conserved in all eucaryotic cells. We demonstrated structural and functional conservation of the rate-limiting enzyme of the mammalian pathway, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoA reductase), between the yeast Saccharomyces cerevisiae and humans. The amino acid sequence of the two yeast HMG-CoA reductase isozymes was deduced from DNA sequence analysis of the HMG1 and HMG2 genes. Extensive sequence similarity existed between the region of the mammalian enzyme encoding the active site and the corresponding region of the two yeast isozymes. Moreover, each of the yeast isozymes, like the mammalian enzyme, contained seven potential membrane-spanning domains in the NH2-terminal region of the protein. Expression of cDNA clones encoding either hamster or human HMG-CoA reductase rescued the viability of hmg1 hmg2 yeast cells lacking this enzyme. Thus, mammalian HMG-CoA reductase can provide sufficient catalytic function to replace both yeast isozymes in vivo. The availability of yeast cells whose growth depends on human HMG-CoA reductase may provide a microbial screen to identify new drugs that can modulate cholesterol biosynthesis.

Triazole resistant Aspergillus fumigatus in an Israeli patient with Chronic Cavitary Pulmonary Aspergillosis due to a novel E306K Substitution in Hmg1

2021 ◽  
Author(s):  
Mariana Handelman ◽  
Alma Morogovsky ◽  
Wei Liu ◽  
Ronen Ben-Ami ◽  
Nir Osherov
Keyword(s):  
Aspergillus Fumigatus ◽  
Coenzyme A ◽  
Pulmonary Aspergillosis ◽  
Hmg Coa Reductase ◽  
Therapeutic Challenge ◽  
Reductase Gene ◽  
Coa Reductase

Triazole resistance in the pathogenic mold Aspergillus fumigatus has increased worldwide, posing a growing therapeutic challenge. Recently, mutations in the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase gene ( hmg1 ) have been associated with triazole resistance. Here, we describe a novel E306K triazole resistance-conferring mutation in the HMG-CoA reductase gene from an Israeli patient with chronic cavitary pulmonary aspergillosis (CCPA).

scholarly journals Dietary modification of the activation state of intestinal 3-hydroxy-3-methylglutaryl coenzyme a (HMG-CoA) reductase.

1984 ◽  
Vol 48 (11) ◽  
pp. 2745-2751
Author(s):  
Hirosuke OKU ◽  
Akira MORITA ◽  
Takashi IDE ◽  
Michihiro SUGANO
Keyword(s):  
Coenzyme A ◽  
Dietary Modification ◽  
Hmg Coa Reductase ◽  
Coa Reductase
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