Blood disorders lipid metabolism

Disorder of protein metabolism could be noticed in 13% decrease of total protein content in blood serum. The observed hypoproteinemia was stipulated by 25% decrease of albumin fraction. The index showing correlation between the level of middle molecules and total protein was 65% higher in Group 2 indicating prevalence of protein degradation processes over their synthesis. The revealed disorders indicated the development of liver failure syndrome. Profound disorders were also registered in lipid metabolism. We determined the intensification of lipolysis by increase in the concentration of the main lipid fractions in blood serum. The level... 

In addition to commonly determined lipids, the behaviour of plasma carotenoids has been studied by several authors. As early as 1929, Stannus reported an increase of carotenoids in the blood of patients with xanthosis of the skin. More recently, studies by Zollner (1962 b) revealed increases in carotenoids paralleling those in plasma cholesterol. Since carotenoids are of dietary origin, their elevation must be secondary to changes of other lipids or lipoproteins (beta-lipoproteins in particular) which illustrates the difficulties in deciding which changes found in EFH and other disorders of lipid metabolism represent an associated rather than a basic change. Finally, the studies of Pelkonen (1963) should be referred to, in which he reported on the meta holism of vitamin A and D in normal and hyper-cholesterolemic subjects, and on the distribution of these vitamins in the lipoprotein fractions. 

Diabetes mellitus is now recognized as one of the most common and significant diseases facing Americans. It is estimated that I of 4 children bom today will become diabetic in their lifetime because of obesity and inactivity. Also, it has been noted that diabetes has a severe effect on blood vessels, particularly in the pathogenesis of atherosclerosis (blockage of arteries by lipids and plaque), which can lead to myocardial infarction or stroke. Diabetes mellitus is treated as equivalent to a prior cardiovascular event in its risk for future atherosclerotic disease. Diabetes is also associated with immunosuppression, renal insufficiency, blindness, neuropathy, and other metabolic disorders. 

The normal ovarian and adrenal lipid is intracellular, but there is another important situation in which a lipoid mesophase may be present more or less normally, entirely outside cells. This is in the plasma (39), in the low density /3-lipoprotein fraction (Sf 12 to 20). In health, this fraction is low or absent until adult life. It begins to increase in males from about the age of 20 onward in females, it remains low until the menopause, after which it increases rapidly as in males. It can be produced experimentally in rabbits, dogs, fowls, and some other animals by feeding cholesterol. Analogous to this is the pathological increase seen in humans with certain renal and metabolic disorders, especially in diabetes mellitus and in hereditary or essential hyperlipemia, where there is an increase in several fatty components in the blood, with abnormal deposition of fat in various tissues. 

Numerous applications are now encountered where FA chromatographic profiles of a human physiological fluid or tissue are correlated to certain pathological conditions. A few representative examples will now be mentioned that include both free (non-esterified) FA and the saponified lipids. The identification of a methyl-branched FA (phytanic acid) in plasma of the patients with Refsum s disease [360] is now a widely known example of the power of GC in studying various metabolic defects. The profiles of FA from brain ti.ssue lipids were investigated for various neurological disorders [361,362] and in experimental animals [363]. Tichy et al. [364] determined FA in different lipids isolated from the cerebrospinal fluid while the FA profiles in cerebrospinal fluid differ from those in blood serum, no obvious correlations between the FA composition and human neurological complications were established at this time. 

A further group of branched-chain acids differ from those already discussed in that they are produced from isoprenoid precursors and not by the normal de novo pathway or some simple modification of it. These acids are based on the diterpene phytol derived from chlorophyll and the more common acids are phytanic (C20), pristanic (C19) and a Cie homologue. These molecules contain chiral centres and the natural forms are not always the same enantiomer. These acids occur widely, but at low levels, in the lipids of land and aquatic animals and have been identified in ancient sediments. In animals they occur in tissue, milk and blood lipids and are present as trace components of butter fat. The tissue lipids of humans suffering from the rare neurological disorder Refsum s disease contain up to 50% of phytanic acid because of an inability to metabolize this unusual branched-chain acid (Section 12.6). 

Analyses of hair and blood samples for manganese content indicate that subclinical deficiencies of the mineral might aggravate such disorders as growth impairments, bone abnormalities, diabeticlike carbohydrate metabolism, lack of muscle coordination in the newborn, and abnormal metabolism of lipids (fatty acids, choline, and cholesterol). 

The most widely known metabolic disorders are those which result in impairment of the intermediary metabolism of nutrients such as proteins, carbohydrates and lipids. For example, phenylketonuria is due to a genetic deficiency of phenylalanine hydroxylase, an enzyme involved in the conversion of phenylalanine to tyrosine. As a result, when ingested in amounts normally encountered in the diet, phenylalanine accumulates in blood and cerebrospinal fluid along with its pyruvate, lactate and acetate derivatives. (See review by McBean and Stephenson. ) The toxic response takes the form of severe mental retardation, neural and dermal lesions and premature death. But phenylalanine is an essential dietary amino acid and cannot be rigorously excluded from the diet, even of sufferers from phenylketonuria, though fortunately they do respond to reduced dietary intakes. Clearly, phenylalanine hydroxylase deficiency narrows the gap between the required intake and that which elicits a toxic response because this pathway is more readily overloaded . 

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