Lipoprotein Metabolism and Implications for Atherosclerosis Risk Determination and Treatment Decisions
P. K. Shah in Risk Factors in Coronary Artery Disease, 2006
Lipoproteins are a diverse group of spherical particles that can be separated into various categories based on their density. The regions include triglyceride-rich, VLDL and IDL, and the relatively cholesterol rich LDL. High-density lipoprotein (HDL) particles may play a role in what has been termed “reverse cholesterol transport” (9). In general, the production and metabolism of lipoproteins follows a path of large particles, rich in triglycerols and relatively poor in cholesterol, that undergoes a series of metabolic interactions, which results in more dense particles that are relatively rich in cholesterol and poor in triglycerols. The large triglyceride-rich transport particles, derived from an intestinal source, are termed chylomicrons. The somewhat smaller, triglyceride-rich particles, derived from a hepatic source, are termed VLDL. After a series of interactions with the enzyme lipoprotein lipase (LPL), the particles become more dense and relatively cholesterol rich. An IDL precedes the appearance of LDL, which is normally the greatest source of cholesterol transport among the lipoproteins. Further metabolism involves the interaction of lecithin-cholesterol acyltransferase (LCAT), apoproteins, and neutral exchange factors (10,11). VLDL particles can be produced in both large and smaller forms and through pathways that involve lipoprotein and hepatic lipase (HL), and cholesteryl ester transfer protein (CETP), develops into either large or small LDL particles (Fig. 1) (12,13).
Liver Function Tests in the Differential Diagnosis of Hepatotoxicity
Robert G. Meeks, Steadman D. Harrison, Richard J. Bull in Hepatotoxicology, 2020
It is not surprising that a variety of changes in the levels of various lipids and lipoproteins occur in hepatobiliary disorders since the liver is so intimately involved in lipid metabolism. Serum triglycerides, phospholipids, fatty acid acids, and total cholesterol and its ester are occasionally used to differentiate cholestatic from necrotic processes (Bass et al., 1976). Although changes in triglycerides and total cholesterol levels are not liver-specific, the percent of cholesterol ester (CE) or the occurrence of a unique “lipoprotein-X” (LP-X) can suggest hepatocellular deficiencies or cholestasis, respectively, may be present (Kaplowitz et al., 1982). In hepatocellular disorders, less CE is formed due to low lecithin cholesterol acyltransferase (LCAT) activity in the liver. Elevated levels of both total cholesterol and LP-X are observed in animals with biliary obstruction (Sabesin, 1982). Normal lipoproteins are spherical bodies, while the abnormal LP-X is spherical in structure (Monzato et al., 1976). After the elimination of extrahepatic obstruction in animals, LP-X quickly disappears from the plasma and hepatic LCAT activity returns (Ritland and Bergan, 1975). Although LP-X is not more sensitive than other tests to detect cholestasis, it is another useful test that could be used. The density classes of lipoproteins (VLDL; LDL; HDL; HDL2) are also occasionally measured and are altered significantly in hepatobiliary disorders (Cooper, 1982). There is a need for investigations on such lipids in laboratory animals.
Plasma lipids and lipoproteins
Martin Andrew Crook in Clinical Biochemistry & Metabolic Medicine, 2013
The enzyme lecithin–cholesterol acyltransferase (LCAT) is present on HDL and catalyses the esterification of free cholesterol and is activated by apoA1, the predominant apolipoprotein of HDL. Some HDL particles also contain apoA2. Most of this esterified cholesterol is transferred to LDL, VLDL and chylomicron remnants and thus ultimately reaches the liver. Some may be stored within the core of the HDL particle and taken directly to the liver. Cholesterol ester transfer protein (CETP) is involved in these processes.
Antihyperlipidemic effect of tyrosol, a phenolic compound in streptozotocin-induced diabetic rats
Published in Toxicology Mechanisms and Methods, 2021
Ramasamy Chandramohan, Leelavinothan Pari
Lecithin cholesterol acyltransferase (LCAT) is a crucial enzyme and plays a significant role in removing free cholesterol from tissues via assisting HDL-C maturation, and its activity has been proposed as the primary indicator of HDL-C function. Therefore, if LCAT is impaired, mature HDL generation would presumably be decreased, resulting in augmentation of atherosclerosis (Kripa et al. 2011). In this study, we observed reduced activity of LCAT in plasma signifies the impairment of HDL-C synthesis as well as cholesterol and triglycerides transport and metabolism in STZ-induced diabetic rats. Similarly, our observations coincide with those reported in the study by Pari et al. (2014). Treatment with tyrosol to STZ-induced diabetic rats increases insulin secretion and prevents the accumulation of cholesterol by stimulating the activity of lipid metabolizing enzyme LCAT and catabolic enzymes of cholesterol degradation.
CSL112, a reconstituted, infusible, plasma-derived apolipoprotein A-I: safety and tolerability profiles and implications for management in patients with myocardial infarction
Published in Expert Opinion on Investigational Drugs, 2018
Davide Capodanno, Roxana Mehran, C. Michael Gibson, Dominick J. Angiolillo
CSL112 is a human plasma-derived apoA-I, the primary functional component of HDL [13]. The processes of reverse cholesterol transport and HDL remodeling are schematized in Figure 1 [20]. In the first step of reverse cholesterol transport, lipid-poor apoA-I particles (also known as nascent HDL) interact with the membrane-bound ATP-binding cassette transporter A1 (ABCA1) to accept cholesterol from cells, including macrophages from the arterial wall. The free cholesterol is then esterified by the lecithin–cholesterol acyltransferase enzyme, leading to the formation of mature HDL that can accept cholesterol through other transporters. HDL is then constantly remodeled in the circulation by numerous enzymes and proteins, and cholesterol is finally taken back to the liver for removal. CSL112 acts by promoting cholesterol efflux preferentially through the ABCA1 transporter, which is overexpressed in atherosclerotic plaques.
Hypercholesterolemia due to lipoprotein-X manifesting as pseudohyponatremia in a patient with cholestasis
Published in Baylor University Medical Center Proceedings, 2023
Farhan Azad, Norah Abu Mughaedh, Abdurahman Alloghbi, Ibrahim Tawhari
Symptomatic hyponatremia presents with headache, nausea, vomiting, and feared complications of seizures. Patients can also be asymptomatic if hyponatremia is chronic.4 Before treating, it is important to exclude pseudohyponatremia to avoid complications associated with using isotonic or hypertonic saline. Cholestasis is a common complication of a liver transplant. Given our patient’s recent transplantation and elevated bilirubin and alkaline phosphatase, biliary obstruction and Lp-X–mediated pseudohyponatremia was suspected. Testing for lecithin-cholesterol acyltransferase deficiency, a genetic defect that can raise Lp-X level, was not pursued with the evidence of biliary stricture and cholestasis 2 years after transplantation.5
Related Knowledge Centers
- Cholesteryl Ester
- Enzyme
- Cholesterol
- Lipoprotein
- High-Density Lipoprotein
- Blood Plasma
- Lecithin Cholesterol Acyltransferase Deficiency
- Sterol O-Acyltransferase