Erythrocyte Glutamic Oxaloacetic Transaminase Research Articles

A deficiency of vitamin B 6 is a plausible molecular basis of the retinopathy of patients with diabetes mellitus

Eighteen patients with diabetes mellitus, some of whom had variously retinopathy, pregnancy, and the carpal tunnel syndrome, and were variously treated with steroids and vitamin B 6, have been overviewed for periods of 8 months to 28 years. We have established an association of a deficiency of vitamin B 6 with diabetes by monitoring the specific activity of the erythrocyte glutamic oxaloacetic transaminase and again by the association with the carpal tunnel syndrome (C.T.S.). It has been known for a decade that C.T.S. is caused by a B 6 deficiency. The absence of retinopathy in vitamin B 6-treated diabetic patients over periods of 8 months – 28 years appears monumental. These observations are like discovery and constitute a basis for a new protocol to establish the apparent relationship of a deficiency of vitamin B 6 as a molecular cause of diabetic neuropathy. Blindness and vision are so important that the strength or weakness of the observations are not important; the conduct of a new protocol is important.

Effect of Deficient and Excess Dietary Vitamin B-6 on Amino Transaminase and Glycogen Phosphorylase Activity and Pyridoxal Phosphate Content in Two Muscles from Postpubertal Gilts

Postpubertal gilts averaging 111 kg and gaining 2.7 kg/wk were fed daily 1.9 kg/d of a diet providing 0.45, 2.1 or 83 mg of vitamin B-6/d. An additional group of animals were fed the high vitamin B-6 diet providing 83 mg of vitamin B-6/d for the initial 57 d of the experiment and then switched to 0.45 mg of vitamin B-6/d for the remainder of the 121-d experiment (61 gilts total). On d 0, 57 and 121, animals from each treatment were killed, and samples of the semitendinosus (ST) and semimembranosus (SM) were removed. Glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), glycogen phosphorylase and pyridoxal phosphate (PLP) were measured in muscle tissues. The erythrocyte GOT activity coefficient indicated that gilts consuming 0.45 or 2.1 mg of vitamin B-6/d developed a vitamin B-6 deficiency. A vitamin B-6 deficiency resulted in the loss of whole-muscle transaminase activity (enzyme activity × muscle weight) with little effect on whole-muscle total phosphorylase or total PLP content. Excess dietary vitamin B-6 increased whole-muscle total PLP and total phosphorylase content with small decreases in whole-muscle transaminase. Under these conditions, muscle tissue acts as a nonmobile reservoir of PLP. Sixty to 95% of muscle PLP was bound to muscle glycogen phosphorylase.

Studies on the genetic and non-genetic (physiological) variation of human erythrocyte glutamic oxaloacetic transaminase.

The thermostability profile of seven different electrophoretic variants of human erythrocyte GOT found in 13 different, unrelated families from a racially heterogeneous population was examined. The five different slow-variant and the two different fast-variant classes could be grouped into four different thermostability classes which were termed unstable, less stable, normal and more stable than normal. The thermostability differences among and within the electrophoretic variant classes permitted differentiation of the 13 individuals possessing an electrophoretic variant phenotype into a total of ten different variants.

Tryptophan metabolism in alcoholic pellagra patients: measurements of urinary metabolites and histochemical studies of related muscle enzymes

Biochemical and enzymatic aspects of tryptophan-niacin metabolism were studied in 15 adult alcoholic pellagra patients and in 14 controls. In addition to the clinical signs of niacin deficiency, most of the pellagra patients had other signs of malnutrition. Plasma tryptophan in pellagra patients was 2.07 +/- 1.27 mumol/dl, and in the controls 4.84 +/- 2.21 mumol/dl (p less than 0.001). The erythrocyte glutamic oxaloacetic transaminase index was 1.94 +/- 0.77 in the pellagra patients and 1.58 +/- 0.73 in the controls. The urinary levels of 3-hydroxyanthranilic acid were 34.49 +/- 21.47 mumol/g of creatinine in the pellagra patients and 14.51 +/- 8.02 mumol/g creatinine in the controls (p less than 0.02). The urinary levels of N'methylinicotinamide were 2.13 +/- 1.18 mg/g creatinine in the pellagra patients and 4.76 +/- 1.94 mg/g creatinine in the controls (p less than 0.01). The excretion of N'-methyl-2-pyridone-5-carboxamide (2-pyridone) was 2.94 +/- 2.37 mg/g creatinine in the pellagra patients and 10.19 +/- 7.49 mg/g creatinine in the controls (p less than 0.01). The histoenzymological activity of 3-hydroxyanthranilate oxidase in the deltoid muscle was higher in the pellagra patients than in the controls, whereas alpha-glycerophosphate dehydrogenase activity was higher in the controls. These results suggest that for alcoholic pellagra patients the tryptophan-niacin pathway is inhibited after the 3-hydroxyanthranilate oxidase step.

Apparent inhibition of erythrocyte glutamic oxaloacetic transaminase in subjects on large dosages of B-6.

An apparent inhibition of the erythrocyte glutamic oxaloacetic transaminase E-GOT system of Kishi and Folkers has been observed with erythrocytes from individuals on large amounts of B-6. Evidence is presented that this inhibition is an artefact due to excess pyridoxal phosphate reacting with 2,4,dinitrophenylhydrazine. Excess pyridoxal phosphate competes with pyruvic acid for the available 2,4,dinitrophenylhydrazine which results in a product that is not extractable into toluene, therefore, less chromophore is present as more pyridoxal phosphate is available.

Failure of pyridoxine to improve glucose tolerance in diabetics.

A study was undertaken to test the effect of pyridoxine supplementation on glucose tolerance in diabetes mellitus. Thirteen adult maturity-onset diabetics were studied. Seven were vitamin B6 deficient, as assessed by the stimulation of erythrocyte glutamic oxaloacetic transaminase in vitro by pyridoxal phosphate. All patients received pyridoxine hydrochloride (40 mg twice daily) for 3 weeks. Pyridoxine supplmentation did not bring about any significant alterations in either the oral glucose tolerance or the insulin response to glucose.

Clinical results of a cross-over treatment with pyridoxine and placebo of the carpal tunnel syndrome

Clinical evaluation was made of cross-over treatments by pyridoxine and a placebo of patient 22 having the carpal tunnel syndrome. Extraordinary monitoring of the specific activities of the erythrocyte glutamic oxaloacetic transaminase proved a severe vitamin B6 deficiency, which was partially corrected by the Recommended Dietary Allowance of 2 mg, and completely corrected by 100 mg. The severity of the syndrome diminished on the Recommended Dietary Allowances and the patient was asymptomatic at the higher dosage. On placebo, both the vitamin B6 deficiency and syndrome reappeared. Retreatment with 100 mg again corrected both the deficiency and syndrome. Measurements (total n = 19) of flexion of proximal interphalangeal joints of the index fingers by a goniometer, and of pinch by the Preston gauge revealed objective normalization. Scores of 17 symptoms revealed reductions at both the 2- (P < 0.01) and 100-mg (P < 0.001) dosages. Conduction through the carpal tunnels had improved by electromyography. These and previous data on a total of 22 patients showed the concomitant presence of a deficiency of vitamin B6 and the carpal tunnel syndrome; a causal relationship is apparent.

Vitamin B6 deficiency in uremia

Significant decreases in plasma pyridoxal-5-phosphate (PLP), plasma glutamic-oxaloacetic transaminase (PGOT) and erythrocyte glutamic-oxaloacetic transaminase (EGOT) were found in 29 uremic patients including 14 who had been on hemodialysis an average of 15.8 months. The mean PLP values of the uremic patients (5.39 +/- 0.37 ng/ml) were clearly lower than the values obtained for the normal group (9.30 +/- 0.80 mg/ml). The mean PGOT values of the uremic patients (dialyzed 4.07 +/- 0.29 U/liter, undialyzed 5.31 +/- 0.49 U/liter) were significantly lower than the normal group (6.57 +/- 0.39 U/liter). The mean EGOT value of the uremic patients (325 +/- 17 U/liter) was also lower than normal subjects (416 +/-21 U/liter). Stimulation of the EGOT by exogenous PLP (EGOT index) was less in dialyzed patients (1.60) than normal subjects (1.80) while the undialyzed uremic subjects had a greater than normal stimulation (2.12). All of these results indicate that uremic patients are vitamin B6 deficient and that those undergoing hemodialysis may have decreased amounts of the EGOT apoenzyme.

Effect of oral contraceptives and pyridoxine on the metabolism of vitamin B6 and on plasma tryptophan and alpha-amino nitrogen

The effect of supplementary pyridoxine on the metabolism of vitamin B6 as well as plasma tryptophan and alpha-amino nitrogen was determined in women using oral contraceptive agents. Ten women who were taking oral contraceptive agents and 11 who had never taken them served as subjects. Blood from the various biochemical measurements was drawn from fasting subjects before and after they had received an oral dose of 50 mg of pyridoxine-HCl daily fo 2 days. The use of oral contraceptive agents had no effect on the levels of blood vitamin B6, plasma pyridoxal phosphate, and plasma tryptophan. The activity of erythrocyte glutamic oxaloacetic transaminase was higher (P less than 0.05) in the oral contraceptive agent users than in the nonusers but the stimulation in vitro by pyridoxal phosphate was similar for the two groups. Plasma alpha-amino nitrogen was slightly lower in the oral contraceptive agent users than in the nonusers, but the difference was not statistically significant. The rise in blood vitamin B6 in response to pyridoxine was similar in the two groups, but the rise in plasma pyridoxal phosphate tended to be lower in the oral contraceptive agent treated subjects. Following pyridoxine supplementation, the basal activity of erythrocyte glutamic oxalocetic transaminase increased (P less than 0.01) in both groups of subjects and the stimulation in vitro by pyridoxal phosphate decreased correspondingly. Plasma tryptophan and alpha-amino nitrogen were unaffected by the supplementary pyridoxine.

Aktivitätsmessung der erythrozytären glutamatoxalacetat transaminase unter der einnahme von hormonalen kontrazeptiva und pyridoxin beim menschen

The activity of erythrocyte glutamic-oxaloacetic transaminase and the in vitro stimulation by pyridoxal phosphate have been studied in 13 women taking oral contraceptives. It has been found that the basal enzyme activity was significantly higher in these women compared with a control group. There was no statistical difference between the two groups in the enzyme's in vitro stimulation, so that according to this method no vitamin B 6 deficiency could be observed. Nevertheless it must be supposed that there is an increased requirement for pyridoxal phosphate in women taking oral contraceptives because of the increased activities of B 6-dependent enzymes. In a long term study oral contraceptive users were supplemented with 300 mg pyridoxine hydrochloride per day, which resulted in an extremely high increase of the basal enzyme activity after 3 months. The in vitro stimulation of the enzyme by pyridoxal phosphate soon decreased because of its saturation with coenzyme in vivo. The results are discussed as enzyme induction in women taking estrogen—progesterone-containing contraceptives.

Erythrocyte Glutamic-Oxaloacetic Transaminase (GOT), Glucose-6-Phosphate Dehydrogenase (G-6-PD) and Cholinesterase Determinations in an Automated Analysis System and Its Clinical Significance.

Erythrocyte Glutamic-Oxaloacetic Transaminase (GOT), Glucose-6-Phosphate Dehydrogenase (G-6-PD) and Cholinesterase Determinations in an Automated Analysis System and Its Clinical Significance.

Pyridoxine-Responsive Anemia Conditioned by Isonicotinic Acid Hydrazide

AbstractThree patients are described who had a pyridoxine-responsive anemia while under treatment for pulmonary tuberculosis with INH and PAS. The red cells were hypochromic and target cells were common. Two cases also had microcytosis and one had ringed sideroblasts in the bone marrow. None became hematologically normal with therapy. A somnolent reaction occurred in two of the patients following the parenteral administration of large amounts of pyridoxine, and seemed related to it. The concentration of erythrocyte glutamic oxaloacetic transaminase was less than 25 per cent of the normal mean in two of the patients at the time of relapse.

Large erythrocytes in Down's syndrome: Their significance in relation to enzyme activity, gene dosage, and pyridoxine (B 6) metabolism

A significant macrocytosis as reflected by increased packed cell volume and mean corpuscular volume, was found in a group of 12 institutionalized males with Down's syndrome compared to matched controls. There was no evidence of deficiency of vitamin B~, folic acid, pyridoxine, or iron to explain these differences. To determine whether the observed macrocytosis was attributable to a younger mean RBC age, erythrocyte glutamicoxaloacetic transaminase (EGOT) activity was measured. Also, because of previous reports of impaired tryptophane metabolism in Down's syndrome the question of B6 deficiency was investigated by the in vitro B,-stimulated EGOT; this was normal. However, base-line EGOT activity in the Down's syndrome group was significantly elevated when expressed in relation to red cells but not when related to hemoglobin concentration. This difference was present in both washed RBC and whole blood, although greater in the latter and presumably due to leukocytes with increased enzyme activity. Increased EGOT activity in association with macrocytosis suggests a younger mean cell age of the RBC population in Down's syndrome, and adds support to a similar explanation for the increased enzyme activity of WBC's in these patients, rather than the originally proposed gene dosage hypothesis. Failure to appreciate the macrocytosis in this condition may result in erroneous conclusions regarding the relation of RBC enzyme levels to gene dosage.