Low density lipoprotein-activated lysolecithin acylation by human plasma lecithin-cholesterol acyltransferase. Identity of lysolecithin acyltransferase and lecithin-cholesterol acyltransferase.

Subbaiah, Papasani V.; Albers, J J; Chen, C H; Bagdade, John D.

doi:10.1016/s0021-9258(19)70558-4

Cited by 93 publications

(12 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Positional Specificity of Phospholipase Activities. The LCAT reaction is believed to take place via the formation of an acyl-enzyme intermediate (Subbaiah et al, 1980;). In the absence of an acyl acceptor the enzyme acts as a phospholipase A, releasing the acyl group as FFA.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Role of sn-2 Acyl Group of Phosphatidyl Choline in Determining the Positional Specificity of Lecithin-Cholesterol Acyltransferase

Subbaiah

Liu²,

Paltauf³

1994

Biochemistry

View full text Add to dashboard Cite

Although human plasma lecithin-cholesterol acyltransferase (LCAT) is believed to be specific for the sn-2 position of phosphatidylcholine (PC), our recent studies showed that it derives a significant percent of acyl groups from the sn-1 position of certain PC species. To understand the physicochemical basis for this altered positional specificity, we determined the effect of sn-2 acyl group of PC on the enzyme activity and utilization of 16:0 from the sn-1 position by purified human and rat LCATs. Positional isomers of PC containing 16:0 at sn-2 were better substrates for human LCAT than the corresponding sn-1-16:0 isomers, whereas the reverse was true for rat LCAT. The positional specificity of human LCAT varied greatly depending on the nature of the acyl group at sn-2. The sn-1 contribution from various sn-1-16:0-2-acyl PCs for cholesteryl ester (CE) synthesis was 1.0% from 16:0-16:0, 1.4% from 16:0-20:5, 7.3% from 16:0-18:1, 47.0% from 16:0-20:3, 49.9% from 16:0-20:4, 54.9% from 16:0-22:6, and 72.3% from 16:0-18:0. There was a linear relationship between the percentage of 16:0 CE formed (from sn-1 position) and the acyl chain length at sn-2 position (r = 0.94). Rat LCAT also transferred some 16:0 from sn-1 position of 16:0-22:6, 16:0-20:3, and 16:0-18:0 PCs, but not from the other natural PCs tested. The phospholipase A activity of both LCATs in the presence of 16:0-20:4 PC showed the same positional specificity as CE synthesis, indicating that the specificity is determined at the formation of acyl-enzyme intermediate. These results show that the positional specificity of LCAT is influenced by the structure of PC, especially the chain length of the sn-2 acyl group.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Enzymes. Human plasma LCAT was purified to homogeneity by the procedures described earlier (Subbaiah et al, 1980;Subbaiah et al, 1992). The final preparation had a specific activity of 10-12 nmol of cholesterol esterified/h per pg of protein in the standard proteoliposome assay, using egg PC as the acyl donor (Chen & Albers, 1982).…”

Section: Methodsmentioning

confidence: 99%

Role of sn-2 Acyl Group of Phosphatidyl Choline in Determining the Positional Specificity of Lecithin-Cholesterol Acyltransferase

Subbaiah

Liu²,

Paltauf³

1994

Biochemistry

View full text Add to dashboard Cite

show abstract

“…If a PC molecule becomes partially hydrolyzed by phospholipase A2 or phospholipase A1, one of the two fatty acids bound to the glycerol backbone is removed, and lysophosphatidylcholine (lysoPC) is generated. The production of lysoPC can also result from lecithin-cholesterol acyltransferase (LCAT) activity [ 104 ] or hepatic secretion [ 105 ]. While some PC and lysoPC species seem to possess pro-atherogenic properties, others may have anti-atherogenic qualities.…”

Section: ‘Arteriometabolomics’ Approachmentioning

confidence: 99%

Metabolomics of Arterial Stiffness

Paapstel

Kals

2022

Metabolites

View full text Add to dashboard Cite

Arterial stiffness (AS) is one of the earliest detectable signs of structural and functional alterations of the vessel wall and an independent predictor of cardiovascular events and death. The emerging field of metabolomics can be utilized to detect a wide spectrum of intermediates and products of metabolism in body fluids that can be involved in the pathogenesis of AS. Research over the past decade has reinforced this idea by linking AS to circulating acylcarnitines, glycerophospholipids, sphingolipids, and amino acids, among other metabolite species. Some of these metabolites influence AS through traditional cardiovascular risk factors (e.g., high blood pressure, high blood cholesterol, diabetes, smoking), while others seem to act independently through both known and unknown pathophysiological mechanisms. We propose the term ‘arteriometabolomics’ to indicate the research that applies metabolomics methods to study AS. The ‘arteriometabolomics’ approach has the potential to allow more personalized cardiovascular risk stratification, disease monitoring, and treatment selection. One of its major goals is to uncover the causal metabolic pathways of AS. Such pathways could represent valuable treatment targets in vascular ageing.

show abstract

“…LCAT was purified from human plasma, obtained from a local blood bank, or rat plasma purchased from Pel-Freez Biologics (Rogers, AR). The purification procedures were as described earlier (20,26), using a combination of ultracentrifugation and column chromatography procedures. In many experiments the phenyl Sepharose eluates were used as the enzyme source, rather than the highly pure preparations, because of the greater stability of the enzyme in phenyl Sepharose eluates.…”

Section: Enzyme and Apo A-i Preparationsmentioning

confidence: 99%

Trans unsaturated fatty acids inhibit lecithin: cholesterol acyltransferase and alter its positional specificity

Subbaiah

Subramanian

Liu

1998

Journal of Lipid Research

View full text Add to dashboard Cite

Although dietary trans unsaturated fatty acids (TUFA) are known to decrease plasma HDL, the underlying mechanisms for this effect are unclear. We tested the hypothesis that the decreased HDL is due to an inhibition of lecithin:cholesterol acyltransferase (LCAT), the enzyme essential for the formation of HDL, by determining the activity of purified LCAT in the presence of synthetic phosphatidylcholine (PC) substrates containing TUFA. Both human and rat LCATs exhibited significantly lower activity ( ؊ 37% to ؊ 50%) with PCs containing 18:1 t or 18:2 t , when compared with the PCs containing corresponding cis isomers. TUFA-containing PCs also inhibited the enzyme activity competitively, when added to egg PC substrate. The inhibition of LCAT activity was not due to changes in the fluidity of the substrate particle. However, the inhibition depended on the position occupied by TUFA in the PC, as well as on the paired fatty acid. Thus, for human LCAT, 18:1 t was more inhibitory when present at sn -2 position of PC, than at sn -1, when paired with 16:0. In contrast, when paired with 20:4, 18:1 t was more inhibitory at sn -1 position of PC. Both human and rat LCATs, which are normally specific for the sn -2 acyl group of PC, exhibited an alteration in their positional specificity when 16:0-18:1 t PC or 16:1 t -20:4 PC was used as substrate, deriving 26-86% of the total acyl groups for cholesterol esterification from the sn -1 position. These results show that the trans fatty acids decrease high density lipoprotein through their inhibition of lecithin: cholesterol acyltransferase (LCAT) activity, and also alter LCAT's positional specificity, inducing the formation of more saturated cholesteryl esters, which are more atherogenic.-Subbaiah, P. V., V. S. Subramanian, and M. Liu. Trans unsaturated fatty acids inhibit lecithin:cholesterol acyltransferase and alter its positional specificity.

show abstract

Low density lipoprotein-activated lysolecithin acylation by human plasma lecithin-cholesterol acyltransferase. Identity of lysolecithin acyltransferase and lecithin-cholesterol acyltransferase.

Cited by 93 publications

References 20 publications

Role of sn-2 Acyl Group of Phosphatidyl Choline in Determining the Positional Specificity of Lecithin-Cholesterol Acyltransferase

Role of sn-2 Acyl Group of Phosphatidyl Choline in Determining the Positional Specificity of Lecithin-Cholesterol Acyltransferase

Metabolomics of Arterial Stiffness

Trans unsaturated fatty acids inhibit lecithin: cholesterol acyltransferase and alter its positional specificity

Contact Info

Product

Resources

About