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Acyltransferase

About: Acyltransferase is a(n) research topic. Over the lifetime, 2389 publication(s) have been published within this topic receiving 88167 citation(s). The topic is also known as: acyltransferase.
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Journal ArticleDOI
TL;DR: Several indications exist that the acyltransferase reaction is the major source of plasma esterified cholesterol in man, and one possibility is that it plays a role in the transport of cholesterol from peripheral tissues to the liver.
Abstract: Evidence for the existence of a plasma lecithin : cholesterol acyltransferase is reviewed with emphasis not only on the lipid reactants, but also on the lipoprotein "substrates" and "products." The cholesteryl esters of all major lipoprotein classes become labeled when plasma is incubated with cholesterol-(14)C. However, the smaller, lecithin-rich high density lipoproteins appear to be preferred substrates. Most studies of factors that influence the acyltransferase reaction have not adequately distinguished between effects on the enzyme and effects on the lipoprotein substrates. However, the fact that cholesterol esterification is diminished in plasma from eviscerated animals or from patients with reduced liver function suggests that the liver may regulate both the level of the enzyme and that of the substrates. Several indications exist that the acyltransferase reaction is the major source of plasma esterified cholesterol in man. Furthermore, the reaction may have a broader, extracellular function. One possibility is that it plays a role in the transport of cholesterol from peripheral tissues to the liver.

2,314 citations


Journal ArticleDOI
TL;DR: It is demonstrated that SREBP-1 plays a crucial role in the induction of lipogenesis but not cholesterol biosynthesis in liver when excess energy by carbohydrates is consumed.
Abstract: To elucidate the physiological role of sterol regulatory element-binding protein-1 (SREBP-1), the hepatic mRNA levels of genes encoding various lipogenic enzymes were estimated in SREBP-1 gene knockout mice after a fasting-refeeding treatment, which is an established dietary manipulation for the induction of lipogenic enzymes. In the fasted state, the mRNA levels of all lipogenic enzymes were consistently low in both wild-type andSREBP-1 −/− mice. However, the absence of SREBP-1 severely impaired the marked induction of hepatic mRNAs of fatty acid synthetic genes, such as acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase, that was observed upon refeeding in the wild-type mice. Furthermore, the refeeding responses of other lipogenic enzymes, glycerol-3-phosphate acyltransferase, ATP citrate lyase, malic enzyme, glucose-6-phosphate dehydrogenase, and S14 mRNAs, were completely abolished inSREBP-1 −/− mice. In contrast, mRNA levels for cholesterol biosynthetic genes were elevated in the refedSREBP-1 −/− livers accompanied by an increase in nuclear SREBP-2 protein. When fed a high carbohydrate diet for 14 days, the mRNA levels for these lipogenic enzymes were also strikingly lower in SREBP-1 −/− mice than those in wild-type mice. These data demonstrate that SREBP-1 plays a crucial role in the induction of lipogenesis but not cholesterol biosynthesis in liver when excess energy by carbohydrates is consumed.

632 citations


Journal ArticleDOI
TL;DR: An important role for the enzyme in the pathogenesis of coeliac disease, fibrosis and neurodegenerative disorders has also been demonstrated, making TG2 an important therapeutic target.
Abstract: Transglutaminase 2 (TG2) is an inducible transamidating acyltransferase that catalyzes Ca(2+)-dependent protein modifications. It acts as a G protein in transmembrane signalling and as a cell surface adhesion mediator, this distinguishes it from other members of the transglutaminase family. The sequence motifs and domains revealed in the recent TG2 structure, can each be assigned distinct cellular functions, including the regulation of cytoskeleton, cell adhesion and cell death. Ablation of TG2 in mice results in impaired wound healing, autoimmunity and diabetes, reflecting the number and variety of TG2 functions. An important role for the enzyme in the pathogenesis of coeliac disease, fibrosis and neurodegenerative disorders has also been demonstrated, making TG2 an important therapeutic target.

559 citations


Journal ArticleDOI
TL;DR: Rat livers perfused without added plasma proteins suggest that the liver secretes disk-shaped lipid bilayer particles which represent both the nascent form of high density lipoproteins and preferred substrate for lecithin-cholesterol acyltransferase.
Abstract: Rat livers were perfused for 6 h without added plasma proteins using washed erythrocytes and buffer in a recirculating system. An inhibitor to the enzyme lecithin-cholesterol acyltransferase (5,5'-dithionitrobenzoic acid) was added in some experiments to prevent modification of substrate-lipids contained in secreted lipoproteins. The inhibitor did not detectably alter hepatic ultrastructure or gas exchange, but it inhibited the secreted lecithin-cholesterol acyltransferase by more than 85%. Very low density lipoproteins in perfusate were unaltered but the high density lipoproteins obtained from livers perfused with the inhibitor appeared disk-shaped in negative stain by electron microscopy with a mean edge thickness of 46 +/- 5 A and a mean diameter of 190 +/- 25 A. The high density lipoproteins were composed predominantly of polar lipids and protein with only small amounts of cholesteryl esters and triglycerides. The major apoprotein of these discoidal fractions had the same electrophoretic mobility as the arginine-rich apoprotein, whereas plasma high density lipoproteins contained mainly the A-I approtein. In all these respects the discoidal perfusate high density lipoproteins closely resemble those found in human plasma which is deficient in lecithin-cholesterol acyltransferase. Perfusate high density lipoproteins obtained in the absence of the enzyme inhibitor more closely resembled plasma high density lipoproteins in chemical composition (content of cholesteryl esters and apoproteins) and in electron microscopic appearance. Purified lecithin-cholesterol acyltransferase synthesized cholesteryl esters at a substantially faster rate from substrate lipids of perfusate high density lipoproteins than those from plasma. The discoidal high density lipoproteins were the best substrate for this reaction. Thin sections of plasma high density lipoproteins indicated a spherical particle whereas discoidal high density lipoproteins stained with the characteristic trilaminar image of membranes. These observations suggest that the liver secretes disk-shaped lipid bilayer particles which represent both the nascent form of high density lipoproteins and preferred substrate for lecithin-cholesterol acyltransferase.

523 citations


Journal ArticleDOI
TL;DR: The roles of the Niemann-Pick type C1 protein in mediating the endosomal transport of LDL-derived cholesterol and endogenously synthesized cholesterol are discussed and a close relationship between the ACAT substrate pool and the cholesterol efflux pool is proposed.
Abstract: Mammalian cells acquire cholesterol from low-density lipoprotein (LDL) and from endogenous biosynthesis. The roles of the Niemann-Pick type C1 protein in mediating the endosomal transport of LDL-derived cholesterol and endogenously synthesized cholesterol are discussed. Excess cellular cholesterol is converted to cholesteryl esters by the enzyme acyl-coenzyme A:cholesterol acyltransferase (ACAT) 1 or is removed from a cell by cellular cholesterol efflux at the plasma membrane. A close relationship between the ACAT substrate pool and the cholesterol efflux pool is proposed. Sterol-sensing domains (SSDs) are present in several membrane proteins, including NPC1, HMG-CoA reductase, and the SREBP cleavage-activating protein. The functions of SSDs are described. ACAT1 is an endoplasmic reticulum cholesterol sensor and contains a signature motif characteristic of the membrane-bound acyltransferase family. The nonvesicular cholesterol translocation processes involve the START domain proteins and the oxysterol binding protein-related proteins (ORPs). The properties of these proteins are summarized.

473 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20221
202145
202048
201952
201859
201756

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Topic's top 5 most impactful authors

Rosalind A. Coleman

28 papers, 2K citations

Charles O. Rock

25 papers, 1.2K citations

Robert M. Bell

18 papers, 974 citations

Antoni R. Slabas

11 papers, 322 citations

Margrit Frentzen

11 papers, 320 citations