ISSN:0957-9672    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The availability of the sequenced genome ofSaccharomyces cerevisiae(yeast) has culminated in the use of this model eukaryote to study human diseases at a basic level. This article describes the advantages of studying lipid metabolism in this genetically facile organism, including examples of conserved functions and genetic approaches to identifying new components of cholesterol homeostasis. Curr Opin Lipidol 9:85–91. © 1998 Rapid Science Ltd

ISSN:0957-9672    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Hydroxymethylglutaryl‐coenzyme A reductase degradation occurs in the endoplasmic reticulum, and is regulated by the mevalonate pathway. In order to discover the molecules that mediate the degradation process and its control, we conducted a genetic analysis of the degradation of the yeast Hmg2p isozyme of hydroxymethylglutaryl‐coenzyme A reductase. Hmg2p degradation occurs by the action ofHRDgenes that direct Hmg2p to the ubiquitin‐proteasome pathway. Regulation ofHRD‐dependent Hmg2p degradation appears to occur by the action of a separate set of CRD genes. Curr Opin Lipidol 9:93–97. © 1998 Rapid Science Ltd

ISSN:0957-9672    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Proteins that contain a carboxyl‐terminal CaaX motif undergo post‐translational processing involving prenylation, endoproteolysis and methylesterification. Two yeast genes,AFC1andRCE1, which are candidates for genes encoding CaaX converting enzymes, were recently identified. Rce1p is required for the full penetrance of the activated Ras2pval19phenotype in yeast, indicating its possible utility as a new target in Ras‐based malignancies. Advances in our current understanding of CaaX convertases and the functional importance of CaaX proteolysis are discussed. Curr Opin Lipidol 9:99–102. © 1998 Rapid Science Ltd

ISSN:0957-9672    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Extensive manipulation of the apolipoprotein B gene in yeast and bacterial artificial chromosome clones and subsequent expression of these clones in transgenic mice have provided fresh insights into several aspects of apolipoprotein B biology, including the identification of sequences important for lipoprotein (a) assembly, the demonstration that intestinal expression of apolipoprotein B is controlled by DNA sequences >50 kb from the gene, and the extraordinary finding that apolipoprotein B is expressed in the heart. Curr Opin Lipidol 9:103–111. © 1998 Rapid Science Ltd

ISSN:0957-9672    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The addition of a 7‐hydroxyl group is an early and often rate‐limiting step in the synthesis of bile acids. This reaction is catalysed by two cytochrome P450 enzymes known as cholesterol 7α‐hydroxylase and oxysterol 7α‐hydroxylase. cDNAs encoding these proteins have been isolated and used to define two evolutionarily conserved pathways that produce 7α‐hydroxylated bile acids. Curr Opin Lipidol 9:113–118. © 1998 Rapid Science Ltd

ISSN:0957-9672    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Acyl coenzyme A:cholesterol acyltransferase (ACAT) (EC 2.3.1.26) is an enzyme, located in the endoplasmic reticulum of many types of cells, that catalyzes cholesterol ester formation from cholesterol and fatty acyl CoA substrates. Sterol esterification by ACAT or homologous enzymes is conserved in evolution dating back to yeast. The recent cloning of a human cDNA for ACAT, together with genome sequencing projects, has led to the identification of an ACAT gene family and provided molecular tools for determining ACAT’s functionsin vivo. Summarized here is the current knowledge concerning the molecular genetics of ACAT. Curr Opin Lipidol 9:119–;123. © 1998 Rapid Science Ltd

ISSN:0957-9672    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The methylation of phosphatidylethanolamine is an auxiliary pathway for phosphatidylcholine biosynthesis in liver. Two forms of the enzyme, phosphatidylethanolamineN‐methyltransferase, which catalyses this reaction, are located on the endoplasmic reticulum and mitochondria‐associated membranes. Both forms are encoded by a single murine gene,Pempt, located on chromosome 11. The expression of the gene begins at birth. An inverse relationship exists between the rate of liver growth and the expression of phosphatidylethanolamineN‐methyltransferase. However, disruption of thePemptgene does not alter liver growth in mice or cause any other obvious phenotype. Curr Opin Lipidol 9:125–130. © 1998 Rapid Science Ltd

ISSN:0957-9672    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Niemann–Pick type C (NPC) is an autosomal recessive lysosomal storage disease. Fibroblasts from individuals with Niemann–Pick type C exhibit defective intracellular cholesterol transport. Linkage analysis has led to the recent cloning of the NPC1 gene on human chromosome 18, which is the major disease locus. Analysis of NPC1 reveals homologies with key regulators of cholesterol homeostasis and aDrosophila morphogenreceptor. Curr Opin Lipidol 9:131–135. © 1998 Rapid Science Ltd

ISSN:0957-9672    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Recent discoveries in the regulation of cholesterol metabolism have documented a two step proteolytic pathway that regulates nuclear targeting of the sterol regulatory element binding proteins. Sterol regulatory element binding protein cleavage activating protein is a newly identified protein that modulates the proteolytic maturation of the sterol regulatory element binding proteins. It contains a domain that is quite similar in sequence to the membrane spanning region of the rate controlling enzyme of cholesterol biosynthesis, 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase. The membrane domain of the reductase is involved in its post‐translational regulation by cholesterol. The molecular defect in the intracellular cholesterol storage disease, Niemann–Pick type C, has also recently been identified. Surprisingly, the affected gene encodes a protein with similarity to the membrane domains that are conserved in 3‐hydroxy‐3‐methylglutaryl reductase and sterol regulatory element binding protein cleavage activating protein. Furthermore, the cell surface receptor for the sterol modified hedgehog morphogen, Patched, also contains a membrane domain with significant similarity to this putative sterol monitoring domain. These recent developments suggest a common mechanism for sensing intracellular sterol levels and cell signaling, which is based on the function of related membrane domains that are contained in key regulatory proteins. Curr Opin Lipidol 9:137–140. © 1998 Rapid Science Ltd

ISSN:0957-9672    

出版商:OVID    

年代:1998

数据来源: OVID