Erythrocyte transaminase activities

A variety of studies have shown that 10% to 20% of the population of developed countries have marginal or inadequate stams, as assessed by erythrocyte transaminase activation coefficient (Section 9.5.36) or plasma pyridoxal phosphate (Section 9.5.1 Bender, 1989b). This may be sufficient to enhance the responsiveness of target tissues to steroid hormones (Section 9.3.3), and may be important in the induction and subsequent development of hormone-dependent cancer of the breast and prostate. Vitamin Be supplementation may be a useful adjunct to other therapy in these common cancers certainly, there is evidence that poor vitamin Be nutritional stams is associated with a poor prognosis in women with breast cancer. 

A number of studies have measured the activation of plasma transaminases by pyridoxal phosphate added in vitro however, it is difficult to interpret the results, because plasma transaminases arise largely accidentally, as a result of cell turnover, and the amount released will depend on tissue damage. Furthermore, there is a considerable amount of pyridoxal phosphate in plasma, largely associated with serum albumin, and the extent to which plasma transaminases are saturated will depend largely on the relative affinity of albumin and the enzyme concerned for the coenzyme, rather than reflecting the availability of pyridoxal phosphate for intracellular metabolism. Studies on erythrocyte transaminase activation coefficient are easier to interpret, because the extent to which the enzymes are saturated depends mainly on the availability of pyridoxal phosphate. 

Early studies of vitamin Be requirements used the development of abnormalities of tryptophan or methionine metabolism during depletion, and normalization during repletion with graded intakes of the vitamin. Although tryptophan and methionine load tests are unreliable as indices of vitamin Be status in epidemiological studies (Section 9.5.4 and Section 9.5.5), under the controlled conditions of depletion/repletion studies they do give a useful indication of the state of vitamin Be nutrition. More recent studies have used more sensitive indices of status, including the plasma concentration of pyridoxal phosphate, urinary excretion of 4-pyridoxic acid, and erythrocyte transaminase activation coefficient. 

A more specific type of chemical assay is based on enzymatic measurement of vitamin co-enzyme activity. This approach is designed to detect a vitamin deficiency in tissues, and is only feasible for those vitamins that serve as co-enzymes. For instance, thiamin depletion in a subject can be diagnosed by measuring the transketolase activity in red blood cells with and without the addition of thiamin pyrophosphate (TPP) in vitro. If TPP increases the activity by more than a given amount, thiamin deficiency is indicated. Similarly, a subnormal level of riboflavin is indicated in tissues if the activity of erythrocyte glutathione reductase is increased after the addition of flavin adenine dinucleotide (FAD). Erythrocyte transaminase activation by pyridoxal-5 -phosphate (PLP) can be measured to establish a deficiency of vitamin B . 

A number of studies have shown that between 10 and 20% of the apparently healthy population have low plasma concentrations of pyridoxal phosphate or abnormal erythrocyte transaminase activation coefficient, suggesting vitamin Bg inadequacy or deficiency. In most studies, only one of these indices of vitamin Bg nutritional status has been assessed. Where both have been assessed, while each shows some 10% of the population apparently inadequately provided with vitamin Bg, few of the subjects show inadequacy by both criteria. 

Transaminase activities can be measured in plasma, erythrocytes, and leukocytes, and erythrocyte levels appear to be most valuable in assessing vitamin Be status (S4). A better indication is obtained also if erythrocyte glutamate-pyruvate transaminase (EGPT) and glutamate-oxaloacetate transaminase (GOT) activities are measured before and after the in... 

Since concentration measurements in blood may not reflect true vitamin status, the measurement of metabolites or activity of enzymes that use a coenzyme form of a B vitamin has been suggested. For example, the measurement of either homocysteine or methylmalonic acid has been suggested as a marker for cobalamin status, and the erythrocyte transaminase coefficient has been suggested as a marker for vitamin Bg status. However, there are no accepted definitions for the diagnosis of vitamin deficiency in the case of many vitamins. 

The most widely used method of assessing vitamin B status is by the activation of erythrocyte transaminases by pyridoxal phosphate added in vitro, expressed as the activation coefficient (section 11.6.4.1). The ability to metabolize a test dose of tryptophan (section 11.9.5.1) or methionine (section 11.9.5.2) has also been used. 

Mitotane is an inhibitor of intramitochondrial synthesis of pregnenolone and cortisol, used to produce a chemical adrenalectomy in the treatment of adrenal carcinoma and Cushing s disease and syndrome. Its unwanted effects include increased transaminase and alkaline phosphatase activities, reduced leukocjrte, platelet and erythrocyte counts, and myasthenia (1). 

In a report dating from 1987, low selenium concentrations were found in four children receiving long-term parenteral nutrition. There was erythrocyte macrocytosis (n — 3), loss of pigmentation of hair and skin (n = 2), raised transaminase and creatine kinase activities (n — 2), and profound muscle weakness n = 1). Intravenous supplementation with selenium for 3-12 months resulted in progressive improvement in all these (70). 

In 15 patients who had a serious adverse reaction to valproate (including behavioral changes and emesis in six, raised aspartate transaminase in three, raised aspartate transaminase and pancreatitis in one, thombocytopenia in two, and unexpected death in two), erythrocyte glutathione peroxidase activity and plasma selenium and zinc concentrations were significantly reduced, whereas erythrocyte glutathione reductase activity was significantly raised... 

Various pyridoxal phosphate dependent enzymes compete with each other for the available pool of coenzyme. Thus the extent to which an enzyme is saturated with its coenzyme provides a means of assessing the adequacy of the body pool of coenzyme. This can be determined by measuring the activity of the enzyme before and after the activation of any apoenzyme present in the sample by incubation with pyridoxal phosphate added in vitro. Erythrocyte aspartate and alanine transaminases are both commonly used the results are usually expressed as an activation coefficient— the ratio of activity with added coenzyme to that without. 

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