RESUMEN
The alteration in the metabolic activation of N-nitrosodimethylamine (NDMA) was investigated in the rat during dietary pyridoxine deficiency. The in vitro metabolism of NDMA by demethylase system was measured in both liver and kidney microsomes. The profile of the kidney enzyme appears similar to that of the liver indicating that at least two forms of isozymes with the low and the high Km's are present. Pyridoxine deficiency significantly increased the activity of NDMA-demethylase of both organs. The increase in the activity of NDMA-demethylase induced by dietary pyridoxine deficiency can be reversed by supplementation of pyridoxine (500 micrograms), i.p., daily for two consecutive days. The increase in the NADPH cytochrome c reductase activity was observed after 6 weeks on pyridoxine-deficient diet.
Asunto(s)
Sistema Enzimático del Citocromo P-450/metabolismo , Dimetilnitrosamina/metabolismo , Oxidorreductasas N-Desmetilantes/metabolismo , Deficiencia de Vitamina B 6/enzimología , Animales , Citocromo P-450 CYP2E1 , Riñón/enzimología , Cinética , Masculino , Microsomas/enzimología , Microsomas Hepáticos/enzimología , Ratas , Ratas Endogámicas F344RESUMEN
Previous reports indicated that in growing rats the vitamin B-6 pool in muscle was relatively stable during deficiency but increased in response to increased vitamin B-6 intake. To determine whether human muscle would show a similar response 10 college-aged males received a low vitamin B-6 diet (1.76 mumol/d) for 6 wk followed by 6 wk on a self-selected diet supplemented with 0.98 mmol pyridoxine HCl/d. During depletion, excretion of pyridoxic acid rapidly adjusted to approximate the intake. Plasma pyridoxal phosphate concentrations at the end of the baseline, depletion, and supplementation periods were 81 +/- 51, 9 +/- 3, and 455 +/- 129 nmol/L, respectively, whereas muscle concentrations were 21 +/- 9, 20 +/- 4, and 25 +/- 7 nmol/g, respectively and total vitamin B-6 in muscle was 28 +/- 10, 27 +/- 4, and 35 +/- 10 nmol/g, respectively. These data provide further confirmation that the vitamin B-6 pools in skeletal muscle are resistant to depletion. They also demonstrate that in humans with constant body weight, vitamin B-6 supplementation is not associated with marked increases in vitamin B-6 in muscle.
Asunto(s)
Músculos/química , Piridoxina/administración & dosificación , Adulto , Aspartato Aminotransferasas/sangre , Eritrocitos/enzimología , Humanos , Masculino , Fosfato de Piridoxal/sangre , Piridoxina/análisis , Piridoxina/sangre , Piridoxina/orina , Deficiencia de Vitamina B 6/sangre , Deficiencia de Vitamina B 6/enzimologíaRESUMEN
In vitro supplementation with the active form of vitamin B6, pyridoxal-phosphate (PLP), increases measurements of both serum aminotransferase enzymes, L-aspartate: 2-oxoglutarate amino transferase, EC 2.6.1.1 (AST) and L-alanine: 2-oxoglutarate aminotransferase, EC 2.6.1.2 (ALT). The plasma PLP level in normal individuals clearly relates inversely to the degree of stimulation of serum AST and ALT. PLP added in vitro increases the reference values but does not decrease the biological variability of AST measurements in healthy individuals. Since B6 deficiency is observed in alcoholics, in some significant percentage of hospitalized patients and in apparently healthy people over age 64, these individuals will show PLP stimulation of their serum amino-transferase enzymes. Patients with liver disease show lesser activation with PLP of AST activity but not ALT activity than patients with heart disease (myocardial infarction). AST isoenzyme measurements in the form of a mitochondrial AST/total AST ratio may discriminate alcoholic hepatitis from all other hepatic diseases. In renal dialysis patients including transplant patients, it may be desirable to measure the aminotransferases with added PLP in order to reflect better the cytolytic state of the liver. While unconfirmed studies suggest the combination of PLP activation and AST isoenzyme measurements may aid in the diagnosis of hepatoma, PLP activation per se does not provide clear cut improved diagnostic value of AST and ALT in liver diseases. However, in view of PLP incorporation into the IFCC reference methods for AST and ALT, and the National Reference System for the Clinical Laboratory, it is recommended that PLP be included in all AST and ALT measurements.
Asunto(s)
Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Hepatopatías/enzimología , Fosfato de Piridoxal/farmacología , Alcoholismo/metabolismo , Donantes de Sangre , Carcinoma Hepatocelular/enzimología , Activación Enzimática , Humanos , Cinética , Hígado/enzimología , Hepatopatías/sangre , Neoplasias Hepáticas/enzimología , Síndrome de Reye/enzimología , Deficiencia de Vitamina B 6/enzimologíaRESUMEN
The effect of deoxypyridoxine on the activities of drug-metabolizing enzymes was investigated in male rats. Phenylbutazone oxidase and aminopyrine N-demethylase decreased in both liver and kidney of deoxypyridoxine-treated rats that received either an 18% or 8% casein diet. However, the magnitude of decrease in activities was more when the rats received an 8% casein diet. The NADPH oxidase activity remained unchanged following deoxypyridoxine treatment. The diminished activities of phenylbutazone oxidase and aminopyrine N-demethylase noted after deoxypyridoxine treatment were restored by pyridoxine supplementation. The decreased activities of drug-metabolizing enzymes in deoxypyridoxine treated rats were not reversed by thyroxine supplementation. It is suggested that pyridoxine in the form of pyridoxal phosphate might be involved in the regulation of drug-metabolizing activities.
Asunto(s)
Aminopirina N-Demetilasa/metabolismo , Oxidorreductasas/metabolismo , Piridoxina/análogos & derivados , Deficiencia de Vitamina B 6/enzimología , Animales , Caseínas/administración & dosificación , Activación Enzimática/efectos de los fármacos , Riñón/enzimología , Masculino , Microsomas/enzimología , Microsomas Hepáticos/enzimología , Piridoxina/metabolismo , Piridoxina/farmacología , Ratas , Ratas EndogámicasRESUMEN
It was found that under the influence of hydrazine sulfate, which in the dosage of 60 mg/kg would induce a 50% suppression of Walker carcinosarcoma in rats, there is the decreased activity of mitochondrial monoamine oxidase and a sharp reduction in the activity of some microsomal phosphatases. Vitamin B6 injection some hours before injecting hydrazine sulfate lessens the rate of suppression of the tumor growth up to 50%. The results obtained indicate that the antitumor effect of hydrazine sulfate may be related to the suppressed monoamine oxidate activity and vitamin B6 deficiency.
Asunto(s)
Antineoplásicos , Hidrazinas/uso terapéutico , Animales , Carcinoma 256 de Walker/tratamiento farmacológico , Carcinoma 256 de Walker/enzimología , Evaluación Preclínica de Medicamentos , Activación Enzimática/efectos de los fármacos , Hidrazinas/administración & dosificación , Trasplante de Neoplasias , Ratas , Factores de Tiempo , Deficiencia de Vitamina B 6/enzimologíaRESUMEN
Urinary endogenous oxalate was increased by feeding vitamin B6-deficient or control rats with 5.2% hydroxyproline, or 3% glycine plus 5.2% hydroxyproline. The activities of liver lactic dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G6PD) , malic enzyme (ME), and ATP citrate lyase were decreased in vitamin B6-DEFICIENT RATS, AND THEIR LIVEr G6PD was further decreased by the addition of glycine and hydroxyproline to their diets. Supplementing control diets with the two amino acids decreased the activities of rat liver LDH, G6PD, and ATP citrate lyase. The effects of glycine and hydroxyproline feeding on the enzymes studied did not appear related to alterations in insulin availability. Since in vitamin B6-deficient rats, there are increases in urinary levels of oxalic and glycolic acids, and glycine, and increases in tissue levels of glyoxylic acid and glycine, the effects of these metabolites on the activities of the above mentioned enzymes were measured. Oxalic acid inhibited the activities of LDH, G6PD, and ME. Glyoxylic acid inhibited LDH and ME, but not G6PD. Glycolic acid inhibited G6PD and ME, but not LDH. ATP citrate lyase was not affected by these substances. Glycine had no effect on the enzymes studied. Diets which increased oxalate excretion generally reduced or did not alter liver and kidney levels of oxalate, glycolate, and glyoxylate. However, the feeding of glycine and hydroxyproline increased kidney oxalate, and liver and kidney glyoxylate in vitamin B6-deficient rats.
Asunto(s)
Glicina/farmacología , Glicolatos/farmacología , Glioxilatos/farmacología , Hidroxiprolina/farmacología , Hígado/enzimología , Oxalatos/farmacología , Deficiencia de Vitamina B 6/enzimología , ATP Citrato (pro-S)-Liasa/metabolismo , Animales , Glucosafosfato Deshidrogenasa/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Hígado/efectos de los fármacos , Malato Deshidrogenasa/metabolismo , Masculino , RatasRESUMEN
The mean basal specific activity (S.A.) of the glutamic oxaloacetic transaminase of erythrocytes (EGOT) for a group of 64 pregnant women was lower (p less than 0.001) than the value for the cord bloods of newborn infants, and lower (p less than 0.001) than the value for adults who had a top limit of S.A. of EGOT. In establishing the top limit of the S.A., it is important that the mean basal S.A. of the cord bloods from 49 newborn infants was identical to the mean basal S.A. of adults who had an adequate supplement of pyridoxine. There were no differences in the mean basal S.A.'s of the cord bloods between asymptomatic mothers and mothers who had anemia, edema, hypertension, proteinuria and glucosuria. An infant may be born with a top limit of S.A. which is non-deficient in pyridoxal 5'-phosphate, but a mother can have a low level of the transaminase, and which is deficient in the coenzyme.
Asunto(s)
Aspartato Aminotransferasas/sangre , Eritrocitos/enzimología , Sangre Fetal/enzimología , Recién Nacido , Embarazo , Femenino , Humanos , Masculino , Complicaciones del Embarazo/enzimología , Deficiencia de Vitamina B 6/enzimologíaRESUMEN
We describe optimized, ultraviolet spectrophotometric procedures for determination of erythrocyte transketolase, glutathione reductase, and aspartate aminotransferase activity, and their activation by their respective coenzymes--thiamine pyrophosphate, flavin-adenine dinucleotide, and pyridoxal-5-phosphate--as tests for vitamin B1, B2, and B6 deficiency. With these procedures we have investigated healthy subjects on normal and vitamin-supplemented diets, and a series of (mainly) alcoholic hospital in-patients. The enzyme procedures described have good precision and can be readily carried out in the routine laboratory. Abnormal transketolase activation correlated well with clinical evidence of vitamin B1 deficiency.
Asunto(s)
Aspartato Aminotransferasas/sangre , Eritrocitos/enzimología , Flavina-Adenina Dinucleótido , Glutatión Reductasa/sangre , Fosfato de Piridoxal , Tiamina Pirofosfato , Transcetolasa/sangre , Deficiencia de Vitamina B/diagnóstico , Eritrocitos/efectos de los fármacos , Cinética , Deficiencia de Riboflavina/diagnóstico , Deficiencia de Riboflavina/enzimología , Deficiencia de Tiamina/diagnóstico , Deficiencia de Tiamina/enzimología , Deficiencia de Vitamina B 6/diagnóstico , Deficiencia de Vitamina B 6/enzimologíaRESUMEN
Induction of tyrosine aminotransferase (TAT) (EC 2.6.1.5) by hydrocortisone was studied during cofactor (pyridoxal phosphate) depletion in hepatoma-bearing BUF strain female rats. Pairs of rats were matched for weight and age and one from each pair was fed ad libitum a diet lacking pyridoxine; the other (referred to as "pair-fed") was given the same diet supplemented with the vitamin, with the amount restricted to that consumed by the matched animal on the deficient diet. All animals were inoculated with Morris hepatoma no. 7777 cell after 21 days on the respective diets. TAT specific activity was determined weekly in host liver and hepatoma, in the presence and absence of cofactor, before and after the administration of hydrocortisone. Free and bound pyridoxal phosphate was estimated enzymatically. The average weight of hepatomas from pair-fed animals was 1.5-fold to twofold greater than that of hepatomas from animals on deficient diets. TAT activity of hepatomas was two times greater than that of host liver, and lack of dietary pyridoxine was without effect. Hormonal induction of enzymatic activity was maximal after the first week of tumor growth and subsequently reached minimal values. In pair-fed animals, tumor TAT was approximately 60% saturated with cofactor. In vitamin-deficient animals, only 6% of the tumor enzyme was saturated with the cofactor. The percent saturation of host liver TAT varied, with minimal values found in the vitamin-deficient animals. Hepatic and tumor pyridoxal phosphate content of pair-fed animals was unusually high (10 mug/g); in vitamin-deficient animals, only the coenzyme content of hepatomas was high (7.0 mug/g). The results showed that presence of the tumor altered the a) specific activity level of TAT and tissue content of cofactor, b) pattern of hormonal induction of the enzyme, and c) effects of the absence of dietary pyridoxine on TAT induction observed in animals without tumors.
Asunto(s)
Carcinoma Hepatocelular/enzimología , Hidrocortisona/farmacología , Neoplasias Hepáticas/enzimología , Hígado/enzimología , Tirosina Transaminasa/biosíntesis , Deficiencia de Vitamina B 6/enzimología , Animales , Carcinoma Hepatocelular/metabolismo , Inducción Enzimática , Femenino , Hígado/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Experimentales/enzimología , Piridoxina/metabolismo , Ratas , Ratas Endogámicas BUFRESUMEN
The effect(s) of dietary pyridoxine availability on serine dehydratase (SD) specific activity levels of normal liver. Morris hepatomas "5123A, 7316B, 7800, and of respective host livers was studied. Buffalo female weanling rats were fed ad libitum a pyridoxine-free diet or the same diet supplemented with the vitamin. They were inoculated intramuscularly in the hind leg muscles with hepatoma cells after 3 weeks on the respective diets, and those bearing hepatomas "5123A, 7316B, 7800 were killed at 28, 30, and 48 days, respectively, after inoculation. SD activity was highly affected by pyridoxine. Absence of the vitamin from the diet resulted in greatly reduced activity levels in normal liver and the three hepatomas. Tumors grown in animals fed the pyridoxine-supplemented diet had 39j ("5123A), 3.5 ("7316B), and 2.1 ("7800) times more SD specific activity tan respective tumors grown in animals fed the deficient diet. A 1.7-fold increase was observed in normal liver. In contrast to these findings, the specific activity of the enzyme was reduced by 6.3, 1.5, and 3.0 times, respectively, in the host livers of animals fed the vitamin-supplemented diet and bearing hepatomas "5123A, 7316B, and 7800. Serine dehydratase activity depends greatly on dietary vitamin B6 and hence I propose that activity levels in vivo are regulated by its presence or absence.