E3 deficiency

H21. Hazzard, W. R., Wamick, G. R., Utermann, G., Albers, J. J., and Lewis, B., The complex genetics of Type III hyperlipoproteinemia Influence of co-inherited monogenic hyperlipidemia upon the phenotypic expression of apolipoprotein E3 deficiency. In Atherosclerosis V (A. M. Gotto, Jr., L. C. Smith, and B. Allen, eds.), pp. 260-263. Springer-Verlag, Berlin and New York, 1980. 

Pyruvate decarboxylase Ei deficiency Pyruvate decarboxylase E3 deficiency... 

The 2-ketoglutarate dehydrogenase (2-KGD) complex is composed of three separate enzymes 2-ketoglutarate decarboxylase, or El lipoate succi-nyltransferase, or E2 and lipoamide dehydrogenase, or E3. The complex catalyses the oxidation of 2-ketoglutarate to yield succinyl-CoA and NADH. 2-KGD deficiency together with pyruvate dehydrogenase deficiency and branched chain ketoacid decarboxylase deficiency has been ascribed to E3 deficiency because the three enzyme complexes have the E3 component in common. E3 deficiency will not be discussed. 

Familial type III hyperlipoproteinemia (broad beta disease, remnant removal disease, familial dysbetalipoproteinemia) Deficiency in remnant clearance by the liver is due to abnormality in apo E. Patients lack isoforms E3 and E4 and have only E2, which does not react with the E receptor. Increase in chylomicron and VLDL remnants of density < 1.019 (P-VLDL). Causes hypercholesterolemia, xanthomas, and atherosclerosis. 

Wohlfert EA, Gorelik L, Mittler R, Flavell RA, Clark RB Cutting edge deficiency in the E3 ubiquitin hgase Cbl-b results in a multifunctional defect in T cell TGF-(3 sensitivity in vitro and in vivo. J Immunol 2006 176 1316-1320. 

Harris, J.D., Graham, I.R., Schepelmann, S., et al. (2002) Acute regression of advanced and retardation of early aortic atheroma in immunocompetent apolipoprotein-E (apoE) deficient mice by administration of a second generation (E1-, E3-, polymerase-) adenovirus vector expressing human apoE. Hum. Mol. Genet., 11, 43-58. 

Coenzymes The pyruvate dehydrogenase complex contains five coenzymes that act as carriers or oxidants for the intermediates of the reactions shown in Figure 9.3. Ei requires thiamine pyrophosphate, Ep requires lipoic acid and coenzyme A, and E3 requires FAD and NAD+. [Note Deficiencies of thiamine or niacin can cause serious central nervous system problems. This is because brain cells are unable to produce sufficient ATP (via the TCA cycle) for proper function if pyruvate dehydrogenase is inactive.]... 

Production of LDL from VLDL in the plasma With these modifications, the VLDL is converted in the plasma to LDL. An intermediate-sized particle, the intermediate-density lipoprotein (IDL) or VLDL remnant, is observed during this transition. IDLs can also be taken up by cells through receptor-mediated endocytosis that uses apo E as the ligand. [Note Apolipoprotein E is normally present in three isoforms, E2, E3, and E4. Apo E2 binds poorly to receptors, and patients who are homozygotic for apo E2 are deficient in the clearance of chylomicron remants and IDLs. The individuals have familial type III hyperlipoproteinemia (familial dysbetalipoproteinemia, or broad beta disease), with hypercholesterolemia and premature atherosclerosis. Not yet understood is the fact that the E4 isoform confers increased susceptibility to late-onset Alzheimer disease.]... 

Gpxl-deficient mice Increase in ROS level and in lipid peroxidation level in liver decrease in liver mitochondrial respiratory control ratio and power output index Growth retardation E3... 

Andrews, J. L., Kadan, M. J., Gorziglia, M. I., Kaleko, M. and Connelly, S. (2001). Generation and characterization of El/E2a/E3/E4-deficient adenoviral vectors encoding human factor VIII. Mol. Ther. 3, 329-336. 

At least four cases of PDC deficiency have been described in which the intrinsic defect lay not in the complex per se but in one of the two genetically distinct isozymes required to dephospho-rylate the serine residues of the El a subunit. The clinical signs of PDP deficiency do not distinguish it from primary defects of Ela, El(3, E2, E3, or BE The most telling biochemical abnormality reported to date has been the inability to activate PDC in cells cultured with DCA. However, neither direct measurements of PDP activity nor mutations in the PDP gene have been reported for any published case of phosphatase deficiency. 

Bell JG, Tocher DR, MacDonald FM, Sargent JR. Diets rich in eicosapentaenoic acid and gamma-linolenic acid affect phospholipid fatty acid composition and production of prostaglandins El, E2, and E3 in turbot (Scophthalmus maximus), a species deficient in delta 5 fatty acid desaturase. Prostagland Leukotr Essent Fatty Acids 1995 53 279-86. 

E3. Emmerson, B. T., Thompson, C. J., and Wallace, D. C., Partial deficiency of hypoxanthine-guanine phosphoribosyltransferase Intermediate enzyme deficiency in heterozygote red cells. Ann. Intern. Med. 76, 285-287 (1972). 

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