Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0004153 (
atherosclerosis
)
77,401
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Peripheral lipoprotein lipase (LPL)-mediated lipolysis of triglycerides is the first step in chylomicron/VLDL clearance involving heparan sulfate proteoglycans (HSPGs) displayed at the cell surface of the capillaries in adipose tissue, heart and skeletal muscle. The newly generated chylomicron remnant particles are then cleared by the liver, whereas VLDL remnant particles are either further modified, through the action of hepatic lipase (HL) and cholesteryl ester transfer protein (CETP), into LDL particles or alternatively directly cleared by the liver. Two proteins,
lipase maturation factor 1
(
LMF1
) and glycosylphosphatidylinositol-anchored high density lipoprotein binding protein 1 (GPIHBP1), have been recently identified and have revised our current understanding of LPL maturation and LPL-mediated lipolysis. Moreover, new insights have been gained with respect to hepatic remnant clearance using genetically modified mice targeting the sulfation of HSPGs and even deletion of the most abundant heparan sulfate proteoglycan: syndecan1. In this review, we will provide an overview of novel data on both peripheral TG hydrolysis and hepatic remnant clearance that will improve our knowledge of plasma triglyceride metabolism.
Atherosclerosis
2010 Jul
PMID:The metabolism of triglyceride-rich lipoproteins revisited: new players, new insight. 2011 84
Over a third of the US adult population has hypertriglyceridemia, resulting in an increased risk of
atherosclerosis
, pancreatitis, and metabolic syndrome. Lipoprotein lipase (LPL), a dimeric enzyme, is the main lipase responsible for TG clearance from the blood after food intake. LPL requires an endoplasmic reticulum (ER)-resident, transmembrane protein known as
lipase maturation factor 1
(
LMF1
) for secretion and enzymatic activity.
LMF1
is believed to act as a client specific chaperone for dimeric lipases, but the precise mechanism by which
LMF1
functions is not understood. Here, we examine which domains of
LMF1
contribute to dimeric lipase maturation by assessing the function of truncation variants. N-terminal truncations of
LMF1
show that all the domains are necessary for LPL maturation. Fluorescence microscopy and protease protection assays confirmed that these variants were properly oriented in the ER. We measured cellular levels of
LMF1
and found that it is expressed at low levels and each molecule of
LMF1
promotes the maturation of 50 or more molecules of LPL. Thus we provide evidence for the critical role of the N-terminus of
LMF1
for the maturation of LPL and relevant ratio of chaperone to substrate.
...
PMID:Purification, cellular levels, and functional domains of lipase maturation factor 1. 2490 92
