An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases
Lysophosphatidylcholine (LPC) is increasingly recognized as a key marker/factor positively associated with cardiovascular and neurodegenerative diseases. However, findings from recent clinical lipidomic studies of LPC have been controversial. A key issue is the complexity of the enzymatic cascade in...
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doaj-972df63f20e74e0d99d2dacbfea0953d2020-11-24T23:56:50ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-03-01205114910.3390/ijms20051149ijms20051149An Updated Review of Lysophosphatidylcholine Metabolism in Human DiseasesShi-Hui Law0Mei-Lin Chan1Gopal K. Marathe2Farzana Parveen3Chu-Huang Chen4Liang-Yin Ke5Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 80708, TaiwanCenter for Lipid Biosciences, Kaohsiung Medical University Hospital, Kaohsiung 80708, TaiwanDepartment of Studies in Biochemistry, Manasagangothri, University of Mysore, Mysore-570006, IndiaDepartment of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 80708, TaiwanCenter for Lipid Biosciences, Kaohsiung Medical University Hospital, Kaohsiung 80708, TaiwanDepartment of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 80708, TaiwanLysophosphatidylcholine (LPC) is increasingly recognized as a key marker/factor positively associated with cardiovascular and neurodegenerative diseases. However, findings from recent clinical lipidomic studies of LPC have been controversial. A key issue is the complexity of the enzymatic cascade involved in LPC metabolism. Here, we address the coordination of these enzymes and the derangement that may disrupt LPC homeostasis, leading to metabolic disorders. LPC is mainly derived from the turnover of phosphatidylcholine (PC) in the circulation by phospholipase A2 (PLA2). In the presence of Acyl-CoA, lysophosphatidylcholine acyltransferase (LPCAT) converts LPC to PC, which rapidly gets recycled by the Lands cycle. However, overexpression or enhanced activity of PLA2 increases the LPC content in modified low-density lipoprotein (LDL) and oxidized LDL, which play significant roles in the development of atherosclerotic plaques and endothelial dysfunction. The intracellular enzyme LPCAT cannot directly remove LPC from circulation. Hydrolysis of LPC by autotaxin, an enzyme with lysophospholipase D activity, generates lysophosphatidic acid, which is highly associated with cancers. Although enzymes with lysophospholipase A1 activity could theoretically degrade LPC into harmless metabolites, they have not been found in the circulation. In conclusion, understanding enzyme kinetics and LPC metabolism may help identify novel therapeutic targets in LPC-associated diseases.http://www.mdpi.com/1422-0067/20/5/1149lysophosphatidylcholinelipoprotein-associated phospholipase A2lysophosphatidylcholine acyltransferaselysophospholipase A1autotaxinG protein–coupled receptor G2A |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shi-Hui Law Mei-Lin Chan Gopal K. Marathe Farzana Parveen Chu-Huang Chen Liang-Yin Ke |
spellingShingle |
Shi-Hui Law Mei-Lin Chan Gopal K. Marathe Farzana Parveen Chu-Huang Chen Liang-Yin Ke An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases International Journal of Molecular Sciences lysophosphatidylcholine lipoprotein-associated phospholipase A2 lysophosphatidylcholine acyltransferase lysophospholipase A1 autotaxin G protein–coupled receptor G2A |
author_facet |
Shi-Hui Law Mei-Lin Chan Gopal K. Marathe Farzana Parveen Chu-Huang Chen Liang-Yin Ke |
author_sort |
Shi-Hui Law |
title |
An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases |
title_short |
An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases |
title_full |
An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases |
title_fullStr |
An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases |
title_full_unstemmed |
An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases |
title_sort |
updated review of lysophosphatidylcholine metabolism in human diseases |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-03-01 |
description |
Lysophosphatidylcholine (LPC) is increasingly recognized as a key marker/factor positively associated with cardiovascular and neurodegenerative diseases. However, findings from recent clinical lipidomic studies of LPC have been controversial. A key issue is the complexity of the enzymatic cascade involved in LPC metabolism. Here, we address the coordination of these enzymes and the derangement that may disrupt LPC homeostasis, leading to metabolic disorders. LPC is mainly derived from the turnover of phosphatidylcholine (PC) in the circulation by phospholipase A2 (PLA2). In the presence of Acyl-CoA, lysophosphatidylcholine acyltransferase (LPCAT) converts LPC to PC, which rapidly gets recycled by the Lands cycle. However, overexpression or enhanced activity of PLA2 increases the LPC content in modified low-density lipoprotein (LDL) and oxidized LDL, which play significant roles in the development of atherosclerotic plaques and endothelial dysfunction. The intracellular enzyme LPCAT cannot directly remove LPC from circulation. Hydrolysis of LPC by autotaxin, an enzyme with lysophospholipase D activity, generates lysophosphatidic acid, which is highly associated with cancers. Although enzymes with lysophospholipase A1 activity could theoretically degrade LPC into harmless metabolites, they have not been found in the circulation. In conclusion, understanding enzyme kinetics and LPC metabolism may help identify novel therapeutic targets in LPC-associated diseases. |
topic |
lysophosphatidylcholine lipoprotein-associated phospholipase A2 lysophosphatidylcholine acyltransferase lysophospholipase A1 autotaxin G protein–coupled receptor G2A |
url |
http://www.mdpi.com/1422-0067/20/5/1149 |
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