Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mouse adipsin gene encodes a member of the serine protease family that is expressed predominantly in adipose tissue and is secreted into the bloodstream. Adipsin expression is sharply down-regulated in several models of genetic and acquired obesity, representing the first example of an adipocyte gene whose expression is greatly altered in this disorder. In this study, we have asked whether a DNA fragment from the adipsin gene can direct tissue-specific expression of a heterologous gene and mediate the suppression of this expression in genetic and chemically induced obesity. Transgenic mice have been constructed with 950 bases of DNA from the 5' flanking region of the adipsin gene linked to the bacterial chloramphenicol acetyltransferase (CAT) gene in a mouse strain bearing a recessive obesity gene (diabetes, db). By crossing db/+ transgenic mice with nontransgenic db/+ mice, we obtained progeny that allowed a direct comparison of CAT expression in the tissues of lean and obese littermates. The lean mice express CAT activity predominantly in adipose tissue, while the obese mice show a marked reduction in CAT expression relative to the lean controls. When similar experiments are performed with an adipsin-CAT fusion gene containing a heterologous AKV (AKR mouse leukemia virus) enhancer, the tissue specificity of CAT expression in lean mice is broadened to include the thymus, spleen, brain, and other tissues; down-regulation occurs in all of these tissues in mice homozygous for the obesity gene or in mice that have been injected with monosodium glutamate (MSG), which induces obesity. These results indicate that 950 bases of the 5' flanking region of the adipsin gene carry information that specifies both expression in adipose tissue and a response to a gene or chemical that induces obesity. These results also suggest that the trans-acting factors that are regulated aberrantly in these forms of obesity are not restricted to adipose tissue and could play a role in obesity-linked dysfunctions observed in other tissues as well.
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PMID:Obesity-linked regulation of the adipsin gene promoter in transgenic mice. 279 20

Transcription of the adipocyte-specific adipsin gene is dramatically reduced in the adipose tissue of a number of genetically and chemically-induced obese rodents. To map the region of the adipsin gene that confers this response to obesity, transgenic mice were made containing -114, -250, -400, -700, and -938 base pairs (bp) to +35 bp of the promoter linked to the bacterial chloramphenicol acetyltransferase gene. Transgenic mice containing as few as 114 bp of the adipsin promoter had high levels of chloramphenicol acetyltransferase activity in adipose tissue. However, only those mice with 938 bp of the adipsin upstream regulatory region showed suppression of expression in adipose tissue in mice that were induced to become obese with monosodium glutamate. Using gel retardation assays, we showed that a 56-bp fragment of DNA mapping between -687 and -743 bp upstream from the start of adipsin expression was bound by protein factors in nuclear extracts prepared from adipose tissue. There was much greater retardation of this fragment with nuclear extracts prepared from adipose tissue of lean versus obese mice. These results indicate that a tissue-specific transcription factor(s) that regulates adipsin expression is less active in the adipose tissue of obese animals.
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PMID:Independent regulation of adipose tissue-specificity and obesity response of the adipsin promoter in transgenic mice. 796 1

Tumour necrosis factor-alpha (TNF-alpha) plays a key role in orchestrating the complex events involved in inflammation and immunity. Accordingly, TNF-alpha has been implicated in a wide range of autoimmune and infectious diseases, but also in conditions such as obesity and insulin resistance. The regulation of TNF-alpha expression in man is indicated to be partly genetically determined. We therefore screened a 1263 bp section of the proximal promoter of the TNF-alpha gene for common genetic variants affecting the transcriptional activity of the gene. Here we report the characterization of a common functional polymorphism in the promoter region of the TNF-alpha gene, a C-->A substitution at position -863. Electromobility shift assays provided evidence for a distinct difference in the binding of monocytic and hepatic nuclear factors to the -863C and -863A alleles. The rare -863A allele was associated with 31% lower transcriptional activity ( P < 0.001) in chloramphenicol acetyltransferase (CAT) reporter gene studies in human hepatoblastoma (HepG2) cells, indicating that the-863C/A polymorphism influences the basal rate of transcription of the TNF-alpha gene in vitro. Allele frequencies were 0.83/0.17 amongst 254 apparently healthy men of Swedish origin, aged 35-50 years. In 156 men, the -863C/A polymorphism was associated with the serum TNF-alpha concentration, carriers of the rare A allele having a significantly lower TNF-alpha level ( P < 0.05). It is concluded that the common-863C/A polymorphism in the promoter region of the TNF-alpha gene is functional in vitro in monocytic and hepatic cells and influences the serum TNF-alpha concentration in vivo in healthy middle-aged men.
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PMID:A common functional polymorphism (C-->A substitution at position -863) in the promoter region of the tumour necrosis factor-alpha (TNF-alpha) gene associated with reduced circulating levels of TNF-alpha. 1040 Sep 91

Carnitine acyltransferases catalyze the exchange of acyl groups between carnitine and coenzyme A (CoA). These enzymes include carnitine acetyltransferase (CrAT), carnitine octanoyltransferase (CrOT), and carnitine palmitoyltransferases (CPTs). CPT-I and CPT-II are crucial for the beta-oxidation of long-chain fatty acids in the mitochondria by enabling their transport across the mitochondrial membrane. The activity of CPT-I is inhibited by malonyl-CoA, a crucial regulatory mechanism for fatty acid oxidation. Mutation or dysregulation of the CPT enzymes has been linked to many serious, even fatal human diseases, and these enzymes are promising targets for the development of therapeutic agents against type 2 diabetes and obesity. We have determined the crystal structures of murine CrAT, alone and in complex with its substrate carnitine or CoA. The structure contains two domains. Surprisingly, these two domains share the same backbone fold, which is also similar to that of chloramphenicol acetyltransferase and dihydrolipoyl transacetylase. The active site is located at the interface between the two domains, in a tunnel that extends through the center of the enzyme. Carnitine and CoA are bound in this tunnel, on opposite sides of the catalytic His343 residue. The structural information provides a molecular basis for understanding the catalysis by carnitine acyltransferases and for designing their inhibitors. In addition, our structural information suggests that the substrate carnitine may assist the catalysis by stabilizing the oxyanion in the reaction intermediate.
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PMID:Structure and function of carnitine acyltransferases. 1559 Oct