Deficiency lipid metabolism

GinterE. Marginal vitamin C deficiency, lipid metabolism, and atherosclerosis. Lipid Research 1973 16 162-220. 

Due to the absence of human models for PLTP deficiency, our knowledge about the relevance of plasma PLTP activity for human lipid metabolism is still incomplete. No investigational drugs are available that specifically target the activity of this protein. 

Hessel, S., A. Eichinger et al. (2007). CMOl-deficiency abolishes vitamin a production from 3-carotene and alters lipid metabolism in mice. J. Biol. ChemM706763200 282 33553-33561. 

Glutaric aciduria type II, which is a defect of P-oxida-tion, may affect muscle exclusively or in conjunction with other tissues. Glutaric aciduria type II, also termed multiple acyl-CoA dehydrogenase deficiency (Fig. 42-2), usually causes respiratory distress, hypoglycemia, hyperammonemia, systemic carnitine deficiency, nonketotic metabolic acidosis in the neonatal period and death within the first week. A few patients with onset in childhood or adult life showed lipid-storage myopathy, with weakness or premature fatigue [4]. Short-chain acyl-CoA deficiency (Fig. 42-2) was described in one woman with proximal limb weakness and exercise intolerance. Muscle biopsy showed marked accumulation of lipid droplets. Although... 

Stangl, G.I. and M. Kirchgessner. 1996. Nickel deficiency alters liver lipid metabolism in rats. Jour. Nutr. 126 2466-2473. 

Diabetes mellitus is a very common metabolic disease that is caused by absolute or relative insulin deficiency. The lack of this peptide hormone (see p. 76) mainly affects carbohydrate and lipid metabolism. Diabetes mellitus occurs in two forms. In type 1 diabetes (insulin-dependent diabetes mellitus, IDDM), the insulin-forming cells are destroyed in young individuals by an autoimmune reaction. The less severe type 2 diabetes (non-insulin-dependent diabetes mellitus, NIDDM) usually has its first onset in elderly individuals. The causes have not yet been explained in detail in this type. 

Pantothenic acid is an acid amide consisting of p-alanine and 2,4-dihydroxy-3,3 -di-methylbutyrate (pantoic acid). It is a precursor of coenzyme A, which is required for activation of acyl residues in the lipid metabolism (see pp. 12,106). Acyl carrier protein (ACP see p.l68) also contains pantothenic acid as part of its prosthetic group. Due to the widespread availability of pantothenic acid in food (Greek pantothen = from everywhere ), deficiency diseases are rare. 

The activity of vitamin A is related to vision process, tissue differentiation, growth, reproduction, and the immune system. A deficiency of this micronutrient mainly leads to visual problems, impaired immune function, and growth retardation in children. Hypervitaminosis could lead to hepatotoxicity, affect bone metabolism, disrupt lipid metabolism, and teratogenicity [417]. The isomerization of P-carotene, due to technological processes in foods, leads to a reduction of the vitamin A activity it is therefore important to analyze it. 

Chromium in the +3 oxidation state is an essential trace element (see Section 10.3) required for glucose and lipid metabolism in mammals, and a deficiency of it gives symptoms of diabetes mellitus. However, chromium must also be discussed as a toxicant because of its toxicity in the +6 oxidation state, commonly called chromate. Exposure to chromium(VI) usually involves chromate salts, such as Na2Cr04. These salts tend to be water soluble and readily absorbed into the bloodstream through the lungs. The carcinogenicity of chromate has been demonstrated by studies of exposed workers. Exposure to atmospheric chromate may cause bronchogenic carcinoma with a latent period of 10 to 15 years. In the body, chromium(VI) is readily reduced to chromium(III), as shown in Reaction 10.4.3 however, the reverse reaction does not occur in the body. 

A disorder of lipid metabolism, in which absence of lipoprotein lipase activity due to an absolute apoC-II deficiency results in marked hypertriglyceridemia (Type I phenotype), has been reviewed elsewhere (N8). There are some unexplained differences in the clinical picture and plasma lipoprotein pattern between apoC-II deficiency and primary lipoprotein lipase deficiency. In apoC-II deficiency, symptoms appear to be milder (but recurrent abdominal pain, caused apparently by acute pancreatitis, is a frequently reported symptom). Patients do not show xanthomas or hepatomegaly, and few have splenomegaly (all features of lipoprotein lipase deficiency). Diagnosis is by electrophoresis of the C apolipoproteins, and a plasma triglyceride concentration usually 1000-3000 mg/dl (N8). There may be an increase in plasma VLDL concentration, whereas in classical lipoprotein lipase deficiency plasma VLDL concentration is nearly normal (N8). 

Chromium(III) is an essential nutrient required for normal energy metabolism. The National Research Council (NRC) recommends a dietary intake of 50-200 ig/day (NRC 1989). The biologically active form of an organic chromium(ni) complex, often referred to as GTF, is believed to function by facilitating the interaction of insulin with its cellular receptor sites. The exact mechanism of this interaction is not known (Anderson 1981 Evans 1989). Studies have shown that chromium supplementation in deficient and marginally deficient subjects can result in improved glucose, protein, and lipid metabolism. 

It is apparent that at this stage of development definitive conclusions are premature, and that this aspect of amino acid and lipide metabolism will be pursued vigorously in the near future. It is of considerable interest to us that biotin and pantothenic acid deficiencies affect amino acid transport in L. arabinosus, since both vitamins are known to play a prominent role in lipide biosynthesis. We are currently reexamining the turnover of lipide fractions in nutritionally normal and vitamin-deficient cell types to determine whether there is some relation between this aspect of metabolism and amino acid transport. In any case, the nature of the catalytic steps involved in amino acid transport is still unknown to us. They probably occur in the peripheral cell membrane, but even this elementary and widely accepted belief will require additional study before it can be accepted beyond doubt as an established fact. 

Methionine is intimately related to lipid metabolism in the liver. Methionine deficiency is one of the causes of the fatty liver syndrome. Lack of methionine prevents the methylation of phosphatidylethanolamine to phosphatidylcholine, resulting in an ability by the liver to build and export very low density lipoprotein. The syndrome can be treated by the administration of choline, and for this reason, choline has often been referred to as the lipotropic factor. 

Vanadium Vanadium is believed to be essential in certain animals, although there is still no evidence of this in humans. A V deficiency may alter Fe metabolism, impair heme synthesis, and affect lipid metabolism [15]. 

Because of the blood lowering cholesterol effects of a manganese deficiency, involvement of manganese in lipid metabolism has been a topic of research interest as reviewed by Johnson and Kies in this volume. 

The essentiality of manganese (Mn) for animals was established in 1931 by Orent and McCollum (1) who reported that this element is required for normal reproduction in the rat, and Kemmerer and colleagues (2) who showed that it was necessary for normal growth and reproduction in the mouse. Since then several investigators have verified the critical need of this nutrient for normal development (3). Manifestations of perinatal Mn deficiency in experimental animals include neonatal death, impaired growth, skeletal abnormalities, depressed reproductive function, congenital ataxia, and defects in protein, carbohydrate and lipid metabolism. 

Weanling, Wistar and RICO (genetically hypercholesterolemic) rats were placed on manganese-deficient (0.12 pg Mn/g) or manganese-sufficient (100.12 pg Mn/g) diets. Plasma total, VLDL- and HDL-cholesterol levels, and liver cholesterol and lipid concentrations were not affected by the treatment used. These results suggest that dietary manganese deficiency does not result in significant alterations in cholesterol and lipid metabolism in the rat (8). 

The main effect of riboflavin deficiency is on lipid metabolism. In experimental animals on a riboflavin-free diet, feeding a high-fat diet leads to more marked impairment of growth, and a higher requirement for riboflavin to restore growth. There are also changes in the patterns of long-chain polyunsaturated fatty acids in membrane phospholipids. 

Pyridoxal phosphate has a clear role in lipid metabolism as the coenzyme for the decarboxylation of phosphatidylserine, leading to the formation of phosphatidylethanolamine, and then phosphatidylcholine (Section 14.2.1), and membrane lipids from vitamin Bg-deficient animals are low in phosphatidylcholine (She et al., 1995). It also has a role, less well defined, in the metabolism of polyunsaturated fatty acids vitamin Bg deficiency results in reduced activity of A desaturase and impairs the synthesis of eicosapentanoic and docosahexanoic acids (Tsuge et al., 2000). 

---