Coenzyme risk factors

Diseases of the heart and circulatory system, cardiovascular diseases, have long been the leading cause of mortality in Europe and North America, and total cholesterol and low-density lipoprotein (LDL) cholesterol are the two most important risk factors for coronary heart disease. Decreased arterial compliance of the arteries is thought to contribute to systolic hypertension and coronary artery insufficiency. A number of nutraceuticals have been used for long-term prevention or symptom reduction in cardiovascular diseases, notably soy products, tea flavonoids, octacosanol, n-3-polyunsaturated fatty acids (PUFAs), and, to a lesser extent, melatonin, Pycnogenol, resveratrol, coenzyme QIO, lycopene, and DHEA. 

There are several vitamin Bg-responsive inborn errors of metabolism that include (1) cases of infantile convulsions in which the apoenzyme for glutamate decarboxylase has a poor affinity for the coenzyme (2) a type of chronic anemia in which the number but not morphological abnormality of erythrocytes is improved by pyridoxine supplementation (3) xanthurenic aciduria in which affinity of the mutant kynureninase for PLP is decreased (4) primary cystathion-inuria caused by similarly defective cystathionase and (5) homocystinuria in which there is less of the normal cystathionine synthetase. In these cases increased levels (200 to lOOOmg/day) of administered vitamin Bg are required for life. Low vitamin Bg status (together with low vitamin B12 and folate status) in humans has been linked to hyperho-mocysteinemia and as an independent risk factor for cardiovascular disease. ... 

The role of folic acid in the metabolism of homocysteine has received increased interest recently. Elevations of plasma homocysteine concentrations have been shown to be independent risk factors for coronary artery disease and probably cerebrovascular disease (see Chapter 26). The involvement of folate in its coenzyme forms with homocysteine and methionine metabolism is summarized in Figure 30-22. Folate is the principal micronutrient determinant of homocysteine status, and supplementation with folate has been used as a treatment modality to reduce circulating homocysteine concentrations. Primary (fasting) homo-cystinemia can be treated with 0.5 to 5.0mg/day of folic... 

A comprehensive nutrition assessment must include an evaluation of possible trace element, vitamin, and essential fatty acid deficiencies. Because of their key role in metabolic processes (as coenzymes and cofactors), a deficiency of any of these nutrients may result in altered metabolism and cell dysfunction, and may interfere with metabolic processes necessary for nutritional repletion. The evaluation of single-nutrient-deficiency states includes an accurate history to identify symptoms and risk factors that may indicate deficiency or predispose the patient to developing a deficiency state. A focused physical examination for signs of deficiencies and biochemical assessment to confirm a suspected diagnosis also should be done. Ideally, biochemical assessment would be based on the nutrient s function (e.g., metalloenzyme activity) rather than simply measuring the nutrient s serum concentration. Unfortunately, few practical methods to assess micronutrient function are available currently, and most assays measure serum concentrations of the individual nutrient. 

Cholesterol-Reducing Agents. Hypercholesterolemia is well known as a major risk factor for coronary heart disease. In clinical practice, two main hypocholestrolemic agents are commonly used. One is the 3-hy-droxy-3-methylgrutaryl coenzyme A (HMG-CoA) reductase inhibitors (such as Lipitor) another is the bile acid sequestrants, such as cholestyramine and colestipol (97), which bind bile acid in the intestinal lumen and thus increase their excretion. The main drawback of... 

Background It is well known that hypercholesterolemia is a major risk factor in the progression of atherosclerosis, the major cause of cardiovascular diseases. Statins are widely used to treat hypercholesterolemia. The mechanism of action of these drugs is to reduce the endogenous production of cholesterol by inhibiting 3-hydroxy-3-methylglutaryl coenzyme (HMG-CoA) reductase. Atorvastatin (ATV, Lipitor) is one of the top-selling prescribed oral medications. The only known adverse effect is skeletal muscle toxicity (myopathy) that may be related to the formation of the lactone of the acidic side chain on the molecule. 

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