Glycogenosis type I – von Gierke disease
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
In addition to the hypoglycemia, a variety of abnormalities can be detected in the clinical chemistry laboratory. Lactic acidemia is a regular feature of the disease [30], and occasionally the level of pyruvate is increased. Marked hyperlipidemia and hypercholesterolemia are also features of the disease [12]. Concentrations of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) are high, and the apolipoproteins apoB, C, and E are high, while apoA and D are normal or low [31]. The hyperlipidemia leads not only to the formation of xanthomas, but also to large lipid-laden reticuloendothelial cells in the bone marrow. The plasma may be milky. It is important to recognize that the concentration of water in serum or plasma is markedly reduced in the presence of hyperlipidemia. In as much as electrolytes and other substances are only distributed in the water phase, extremely low values are recorded for the serum sodium and other constituents. A correction must be made for the increased quantity of serum solids and decreased serum water in order to avoid a mistaken diagnosis of hyponatremia.
Enzyme Kinetics and Drugs as Enzyme Inhibitors
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
Plasma lipoprotein particles are aggregates of lipids and proteins with the polar groups of proteins, lipids, and un-esterified cholesterol on their surface and a hydrophobic core consisting of cholesteryl esters and triglycerides. These particles serve to transport the water-insoluble lipids in the blood stream; lipid uptake and release is determined by the interaction between apoproteins (the protein part of the lipoproteins, synthesized mainly in the liver and in the small intestine) and specific receptor proteins of the respective cells. The two major apolipoprotein types are ApoB (550 kDa) which is an integral part of LDL particles (see below) and other, peripheral, apolipoproteins (≈40 kDa and less), subdivided into several classes (Apo A, C, D, E, H) and sub-classes (Apo A-1, A-2, A-IV, A-V), etc., mostly forming HDL lipoprotein. The association with lipid droplets is either irreversible as in the case of Apo B, or reversible and exchangeable between lipoprotein particles.
Pathology, Neurobiology, and Animal Models of Alzheimer’s Disease
Zaven S. Khachaturian, Teresa S. Radebaugh in Alzheimer’s Disease, 2019
ApoE is a 34-kDa glycoprotein and a component of very low-, intermediate-, and high-density lipoproteins and chylomicrons, which transport cholesterol and other lipids.145,146 ApoE, which serves as a ligand for receptor-mediated removal of lipoproteins from plasma, may play roles in immunoregulation and cell proliferation and differentiation.146 ApoE is expressed at high levels in the liver and nervous system and is also the major apolipoprotein in human cerebrospinal fluid.147,148 In the central nervous system, apoE is synthesized and secreted by astrocytes149 and is up-regulated in response to neuronal damage and deafferentation.150,151 Thus, ApoE is implicated in the growth and repair of the nervous system.
An update on emerging drugs for the treatment of hypercholesterolemia
Published in Expert Opinion on Emerging Drugs, 2021
Adam J Nelson, Kristen Bubb, Stephen J Nicholls
Population studies consistently demonstrate a curvilinear relationship between levels of either LDL or total cholesterol and prospective cardiovascular risk [1]. This is supported by the findings of genomic analyses, which consistently demonstrate an association between polymorphisms producing higher LDL cholesterol levels and cardiovascular risk [2]. This extends the role of genetics beyond the major importance of monogenic disorders such as familial hypercholesterolemia in premature cardiovascular disease [3]. Mendelian randomization studies have more reaffirmed this relationship and established a causal role of LDL cholesterol in atherosclerotic cardiovascular disease [2]. Biologic studies have demonstrated the impact of oxidized LDL in the generation of endothelial dysfunction, foam cell formation and orchestration of inflammatory and thrombotic factors implicated in all stages of atherosclerosis [4]. Importantly, each of these studies demonstrate that the relative degree of contribution of different factors on the relationship between LDL cholesterol and cardiovascular risk ultimately depends on variation in levels of apolipoprotein B (apoB). Each of these observations make a strong argument for lowering levels of LDL cholesterol as a priority in the prevention of cardiovascular disease.
Serum apolipoprotein A-I concentration differs in coronary and peripheral artery disease
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2020
Niina Khan, Jahangir Khan, Leo-Pekka Lyytikäinen, Terho Lehtimäki, Jari Laurikka, Niku Oksala
Contemporary serum lipid parameters such as apolipoproteins and lipoprotein subfractions are increasingly recognised as complementary or even superior to the traditional lipid markers in cardiovascular risk assessment. Some guidelines recommend apolipoprotein B (apoB) and/or non-high-density lipoprotein cholesterol (non-HDL-C) measurements [7,8] and lipoprotein(a) – an apolipoprotein A (apoA) particle bound to a LDL-C-like particle – was discovered to be associated with PAD and its progression [9–13]. While the direct methods for obtaining apolipoprotein and lipoprotein subfraction concentrations are resource consuming, these can be estimated from traditional Friedewald inputs – serum TC, triglycerides (TG), and HDL-C – by applying a neural network model, the extended Friedewald formula (EFW), accurately, swiftly and with lower costs [14].
Apolipoprotein E polymorphism carriers exhibit objective cognitive deficits: a single center trial
Published in Neurological Research, 2020
Yanfang Zeng, Xin Huang, Kenneth Elkin, Christopher Stone, Gary B. Rajah, Longfei Guan, Huishan Du, Xiaokun Geng
The apolipoprotein E (ApoE) gene is located on sub-band 2 of band 13 of the long arm of chromosome 19 (19q13.2) [16], and is composed of 299 amino acids reaching a relative molecular mass of 34,000. It is composed of N-terminal and C-terminal domains connected by a single amino acid chain. The N-terminal domain is mainly associated with receptor binding, while the C-terminal domain serves the function of lipid binding. ApoE can be produced in many organs, but its primary synthetic sites are the liver and the brain. In the liver, it is produced and secreted by hepatocytes; this source accounts for 75% of the ApoE found in the blood. ApoE in the brain is produced mainly by astrocytes, followed by microglia, and, under certain conditions and in small amounts, neurons as well. ApoE is one of the major apolipoproteins in the blood, and acts as an essential cholesterol carrier protein in the brain. Under normal physiological circumstances, it plays an important role in plasma lipoprotein metabolism, tissue repair, inhibition of platelet aggregation, and other processes.
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