Pyridoxine-deficient Diet Research Articles

Creatine Metabolism in the Pyridoxine-Deficient Rat

Creatine metabolism was studied in rats fed a pyridoxine-deficient diet for 6–7 wk. Indirect evidence had suggested that creatine levels may be low in these animals, since their livers accumulate a competitive inhibitor of creatine biosynthesis (S-adenosylhomocysteine), and they develop muscle signs suggestive of abnormal creatine metabolism. In contrast, however, the concentration of creatine in both liver and skeletal muscle of pyridoxine-deficient rats was higher than in pair-fed control rats. Pair-fed control rats also had higher creatine levels in liver and skeletal muscle than ad libitum-fed control rats, whose feed intake was about double that of the pair-fed control rats. Thus, feed restriction also increased the tissue creatine levels, and this effect was augmented slightly by pyridoxine deficiency. These changes could not be explained by the results of in vitro measurement of the enzymes of creatine biosynthesis. The activity of guanidoacetate methyltransferase in liver did not differ significantly among the three groups of animals. Kidney arginine-glycine transamidinase activity was noticeably lower in the pyridoxine-deficient rats than in pair-fed control rats and lower in pair-fed control rats than in ad libitum-fed control rats. Since creatinine excretion did not differ significantly among the three animal groups, the results suggest that decreased turnover of creatine may occur during pyridoxine deficiency above and beyond that of an apparent feed restriction alone.

Effect of pyridoxine deficiency on phospholipid methylation in rat liver microsomes.

The effect of altered methionine metabolism during pyridoxine deficiency on the activity of phosphatidylethanolamine methyltransferase (EC 2.1.1.17) and the levels of phosphatidylethanolamine (PE) and phosphatidylcholine (PC) has been evaluated in rat liver microsomes. Animals fed a pyridoxine-deficient diet for 7 wk displayed a fivefold increase in the hepatic tissue level of S-adenosylhomocysteine when compared to either control or pair-fed animal counterparts. When PE methyltransferase was assayed in vitro, a significant increase in specific activity was observed using enzyme preparations from either pair-fed or pyridoxine-deficient rats. On the other hand, phospholipid levels did not conform to the measured enzyme activity. The level of PC in microsomes from either pyridoxine-deficient or pair-fed animal groups was significantly lower than that determined for the control group of rodents. However, the level of PC was noticeably lower in microsomes from pyridoxine-deficient animals than that from pair-fed animals, which received 45% of the feed intake of the control animals. In addition, the level of PE in microsomes from pair-fed and pyridoxine-deficient animals was significantly higher than that analyzed from the control animals, further confirming decreased methylation of substrate to product. It is concluded that pyridoxine deficiency may alter the methylation of phospholipid in the endoplasmic reticulum above and beyond that produced by feed restriction alone.

Putrescine may be a natural stimulator of glucose-6-phosphate dehydrogenase

The possible relationship between pyridoxal phosphate-dependent ornithine decarboxylase (ODC) activity and glucose-6-phosphate dehydrogenase (G6PD) activity has been studied in the osteoblasts of the growthplate of metatarsals of rats fed a pyridoxine-deficient diet, which caused depressed G6PD levels. The G6PD activity was fully restored when it was assayed in the presence of putrescine. It is suggested that this relationship may account for the correlation generally found between growth and ODC activity.

Regulation of rat liver protein methylase III by S-adenosylhomocysteine after D,L-homocysteine thiolactone administration and during pyridoxine deficiency

Since S-adenosylhomocysteine is a potent inhibitor of rat liver protein methylase III in vitro, this enzyme appears to be regulated by modulation of the intracellular molar ratio of S-adenosylmethionine to S-adenosylhomo-cysteine (SAM:SAH ratio). The intraperitoneal administration of D,L-homocysteine thiolactone to animals (500 or 1000 mg/kg), followed by sacrifice 20 minutes later, decreased the SAM:SAH ratio in vivo from 4.35 in the control rats to 1.33 and 0.56 and caused a 62 and 82% inhibition of protein methylase III activity, respectively. Similarily, rats maintained on a pyridoxine-deficient diet for 7 weeks displayed a 5-fold reduction in the hepatic SAM:SAH ratio, when compared either to control or pair-fed counterparts, and a significant 26% reduction in the activity of protein methylase III. Thus, it would appear that a pyridoxine deficiency affects protein methylase III activity via altered SAM:SAH ratios.

Regulation of ornithine aminotransferase in rat kidney by estradiol and pyridoxine.

Increased synthesis of ornithine aminotransferase [EC 2.6.1.13] (OAT) in the kidney of pyridoxine-deficient rats has been reported previously (Ikeda, M. and Okada, M. (1985): J. Nutr. Sci. Vitaminol., 31, 553-561). In this report the effects of 3,3',5'-triiodothyronine (T3) and estradiol on OAT activity in the kidney of rats given pyridoxine-deficient and control diets were studied. T3 induced renal OAT activity in rats given the control diet but not in those given the pyridoxine-deficient diet. On the other hand, estradiol induced renal OAT activity in both deficient and control rats, the levels induced in the two groups being the same. Maximal induction of OAT occurred at a lower dose of estradiol in pyridoxine-deficient rats than in the controls. When rats fed on pyridoxine-deficient diet were pretreated with pyridoxine for several days, OAT induction by estradiol was suppressed. Thus pyridoxal phosphate (PLP) may modulate OAT activity in rat kidney through the action of estradiol.

Changes in renal uptake of Tc-99m methylene diphosphonate (MDP) in stone-forming rats.

A pyridoxine (vitamin B6)-deficient diet in rats was used as a model of early renal lithiasis to find out if "stone-formers" could be identified from control animals by differences in the biodistribution of Tc-99m MDP. The mean renal uptake of this agent at 3 hours was about 70% higher in test animals than in controls, but there was considerable overlap between the upper limits of the normal range and lower values in "stone-formers." If these results were valid for humans, the metabolic abnormality in males with early stone-forming disease could not be identified with certainty by in vivo measurements of Tc-99m MDP renal uptake alone. However, the skeletal uptake of MDP in the "stone-forming" animals was depressed by 28 to 35%, compared with control rats. Consequently, the renal to skeletal MDP concentration ratio was invariably elevated in "stone-formers" beyond the 95 percentile normal range. Unexpectedly, 76% of the pyridoxine-deficient animals had a higher accumulation of MDP in the myocardium than the upper limit of the normal range. The pyridoxine-deficient diet induced no remarkable early changes in the biodistribution or renal clearance of I-131 Hippuran.

Effect of estradiol on the oxalate metabolism in vitamin B 6-deficient male rats

Estradiol-implanted (EB) and sham-operated (SB) male rats (100–120 g body wt) were kept on a vitamin B 6-deficient diet for 1 month along with their respective estradiol pair-fed (EPF) and sham-operated pairfed (SPF) controls. Pyridoxine-deficient animals had higher kidney weights and increased activities of liver glycolic acid oxidase (GAO) and glycolic acid dehydrogenase (GAD) as compared to their pair-fed control animals. Kidney weights, GAO, and GAD levels in these animals are negatively correlated with erythrocyte alanine transaminase (EALT) levels, indicating that pyridoxine status regulates these two major enzymes of oxalate biosynthesis. Estradiol-treated animals showed a lower reduction in FALT levels after feeding them a pyridoxine-deficient diet for 1 month as compared to untreated animals. Estradiol administration decreased GAO levels in both normal and pyridoxine-deficient animals.

The influence of vitamin B6 deficiency on somatosensory stimulus conduction in the rat.

Whilst 22 male Wistar rats were fed on a pyridoxine-deficient diet for 26 weeks, 22 controls received a normal diet. The vitamin B6 deficient animals lost no weight but they developed symptoms of rat pellagra. The sensory nerve conduction velocity, the compound radicular, spinal and brain stem responses and the SEP were derived following tail and hind paw stimulation. The examination was repeated at 6 week intervals. A disturbed central stimulus conduction was indicated by the delayed SEP and intracerebral conduction times. An impairment of neurotransmitter metabolism may be of importance in this case. Considering related data the results implicate the importance of vitamin B6 substitution in the case of CNS disturbances due to malnutrition, e.g., chronic alcoholism. The nerve conduction velocity decreases subsequently. A disturbance of myelin function is indicated in adult rats under conditions of pyridoxine deficiency.

Uptake and processing of serine: pyruvate aminotransferase precursor by rat liver mitochondria in vitro and in vivo.

Processing and uptake of the precursor of serine: pyruvate aminotransferase [EC 2.6.1.51] by mitochondria were studied in vitro and in vivo. Serine: pyruvate aminotransferase was synthesized mainly on free ribosomes as judged by immunoprecipitation of puromycin-labeled nascent peptides prepared from free and bound ribosomes. The precursor of rat liver serine:pyruvate aminotransferase (pSPT) synthesized in vitro was post-translationally processed to an apparently mature form by isolated rat liver mitochondria. Available evidence indicated that the processed product was localized in the matrix of mitochondria. Mature serine:pyruvate aminotransferase did not inhibit the in vitro processing, suggesting that the extra peptide was necessary for the mitochondrial uptake of the precursor. In the livers of rats fed a vitamin B6-deficient high-protein diet, the induction by glucagon of serine:pyruvate aminotransferase occurred and most of the induced enzyme existed in mitochondria as the apo-form, suggesting that pSPT was taken up by mitochondria and processed in the apo-form under the conditions employed. In the in vitro system, on the other hand, the processing of pSPT proceeded both in the absence and presence of pyridoxal 5'-phosphate. Should the precursor also bind the prosthetic molecule, therefore, it would be transported into mitochondria in both the apo- and holo-forms. When isolated rat hepatocytes were labeled with [35S]methionine, labeled pSPT appeared in the cytosolic fraction and was transported rapidly into mitochondria in association with the processing. This uptake and processing were inhibited by a fluorescent laser dye, rhodamine 123, and the precursor accumulated in the cytosol in the presence of the dye.

Vitamin B6 reduces cortisone-induced cleft palate in the mouse.

Administration of Vitamin B6 during gestation to mice on a Vitamin B6-containing diet resulted in a substantial reduction in cortisone-induced cleft palate. Mice maintained on a Vitamin B6-deficient diet demonstrated an increase in the frequency of cortisone-induced cleft palate; this effect was prevented by administration of Vitamin B6. Vitamin B6 inhibited the specific binding of a labeled glucocorticoid to cytosolic receptors from cultured palatal mesenchyme cells. These results indicate that Vitamin B6 reduces the incidence of cortisone-induced cleft palate by altering the binding of glucocorticoids to their cytoplasmic receptors and subsequently nuclear acceptors.

Plasma somatomedin activity, growth-hormone and insulin levels in vitamin B6 deficient rats.

Plasma somatomedin activity was low in rats fed a vitamin B6 deficient diet for 4 weeks. The reduction appears to be in the fraction which is not growth hormone dependent. Plasma growth hormone levels were unaltered while plasma insulin levels were significantly reduced.

Effect of pyridoxine-deficiency on the syntheses of aspartate aminotransferase in rat liver and muscle in vivo.

The rates of synthesis of aspartate aminotransferase isozymes in the liver and skeletal muscle in pyridoxine-deficient rats were examined. The rates of synthesis were compared in rats given pyridoxine-deficient diet ad libitum, rats given control diet ad libitum and rats pair-fed with those on the deficient diet. The rates of incorporation of 3H-L-leucine by both cytosolic and mitochondrial enzymes were highest in pair-fed controls. Incorporation of radioactivity into the cytosolic enzyme was higher in deficient rat liver than in that of controls fed ad libitum, but the rate of incorporation into the mitochondrial enzyme was similar in these two groups. In muscle the rates of incorporation of labeled leucine into both isozymes were similar in all groups when expressed relative to total protein synthesis. It was suggested that increase of glucocorticoid receptor might result in increased synthesis of cytosolic aspartate aminotransferase in pyridoxine-deficient rat liver.

Intestinal Synthesis and Dietary Nonessentiality of Vitamin B12for Tilapia nilotica

Abstract A feeding experiment with purified diets was conducted in a controlled environment to study intestinal synthesis and dietary essentiality of vitamin B12 in Tilapia nilotica. Intestinal microorganisms in T. nilotica fed a vitamin B12-deficient diet synthesized at least 11.2 ng of vitamin B12 per g of body weight per day. Removal of cobalt from the diet or supplementation with an antibiotic (succinylsulfathiazole) significantly reduced the rate of intestinal vitamin synthesis. Dietary supplementation of vitamin B12 was not necessary for normal growth and erythropoiesis or to prevent a decrease in liver-stored vitamin B12 over a 16-week feeding period during which fish weight increased eight-fold.

Sodium and Potassium Chloride Preferences in Pyridoxine-Deficient Rats

AbstractTaste preferences for NaCl and KCl were studied in rats reared from weaning on pyridoxine-deficient or control diets. After 30 days on the diet, the deficient rats showed a markedly enhanced preference for KCl (80.1 vs 32.4%). But there was no significant increase in NaCl preference (85.9 vs 77.6%) which was already high in control rats. The increased KCl preference, along with previous reports of enhanced NaCl preference, reduced sodium secretion, and adrenal hypertrophy is suggestive of possible hyperaldo-steronism in pyridoxine deficiency.

Vitamin B-6 Metabolism and its Relation to Ornithine Decarboxylase Activity in Regenerating Rat Liver

The metabolism of vitamin B-6 in regenerating rat liver and liver from sham-operated control animals fed either a pyridoxine-sufficient or pyridoxine-deficient diet was investigated. The pyridoxal phosphate levels in plasma, regenerating liver and control liver were determined as were the activities of three enzymes involved in the metabolism of the vitamin, namely, pyridoxine kinase, pyridoxine phosphate oxidase, and pyridoxine phosphate phosphatase. In addition, total and holo-ornithine decarboxylase activities in the livers were measured. The results indicate that the metabolism of vitamin B-6 in regenerating rat liver is different from that observed in Morris hepatomas (Thanassi et al. (1981) J. Biol. Chem. 256, 3370–3375). Vitamin B-6 metabolism in Morris hepatomas is concluded to be characteristic of the tumors rather than a property common to rapidly proliferating hepatic tissue. Regenerating liver ornithine decarboxylase holoenzyme activity in pyridoxine deprived rats was maintained at the same level as that in regenerating liver of pyridoxine-sufficient animals. The mechanism behind this maintenance of holo-enzyme activity appears to involve a pronounced increase in the amount of apoornithine decarboxylase. The time-dependent peak of ornithine decarboxylase activity following partial hepatectomy was shifted from four hours to twelve hours by vitamin B-6 deficiency.Vitamin B-6 ornithine decarboxylase regenerating rat liver

Lysosomal changes in fatty liver induced in rats by high protein pyridoxine-deficient diet.

The effect of high-protein pyridoxine-deficient diet on the localization of lysosomes and acid phosphatase activity in the rat liver was studied using light and electron microscopy. Numerous lysosomes containing lipid droplets appeared to arise directly from GERI (Golgi apparatus, endoplasmic reticulum and lysosomes) near bile canaliculi and thereafter large crystal clefts were frequently found in these lysosomes. The increase appearance of lysosomes in hepatocytes was compatible with increased lipid droplets and represented an indication of breakdown of stored lipids. Acid phosphatase activity was localized almost exclusively in lysosomes with or without lipid droplets. We postulated that one of the causes of accumulation of lipid in hepatocytes, including that of triglyceride and cholesteryl ester, might be associated with a relative deficiency of intralysosomal digestion in these conditions.

REPRODUCTIVE PERFORMANCE OF BROILER AND LEGHORN BREEDERS FED CORN-SOYBEAN DIETS WITH GRADED SUPPLEMENTS OF VITAMIN B12

A trial was undertaken to study breed differences in response to vitamin B12 deficient diets. Commercial strain broiler and leghorn breeder hens, 28 wk of age, were fed corn-soybean diets supplemented with either 0.001, 0.002, 0.003, 0.004 or 0.005 mg vitamin B12 per kilogram diet. Each diet was tested with three replicate groups of eight individually caged birds for each strain. Birds were inseminated weekly, and all eggs set for incubation. Over a 24-wk period, diet had no effect on egg production, hatchability of fertile eggs, egg weight or eggshell deformation (P > 0.05). Analysis of diet ingredients indicated substantial quantities of vitamin B12 in both corn and soybean. The possible vitamin availability from such ingredients indicates the unlikely field occurrence of B12 deficiency in breeder hens.

Neurologic Effects of Vitamin B12 Deficiency

Letters1 June 1981Neurologic Effects of Vitamin B12 DeficiencyA. T. MARUBBIO, M.D.A. T. MARUBBIO, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-94-6-823_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In his article on vitamin B12 deficiency caused by a low cholesterol diet in a vegetarian (1), Murphy comments in his penultimate paragraph, "Had he (the patient) continued to eat a folate-rich vitamin B12-deficient diet, serious neurologic sequelae might have developed." In the 1960s, I spent a year in Calcutta and had occasion to speak with the hematologist at the Royal School of Tropical Medicine Hygiene, Dr. Chatterjee. At one point, the topic of neurologic deficiency in vitamin B12 deficiency in vegans came up, and he gave as his opinion that it was unlikely that neurologic deficiency...Reference1. MURPHY M. Vitamin B12 deficiency due to a low-cholesterol diet in a vegetarian. Ann Intern Med. 1981;94:57-8. LinkGoogle Scholar1. BADENOCH J. The use of labelled vitamin B12 and gastric biopsy in the investigation of anaemia. Proc Roy Soc Med. 1954;47:426-7. MedlineGoogle Scholar2. MIRAFALLOWFIELD HJ. Subacute combined degeneration of the spinal cord in a vegan. Postgrad Med J. 1971;47:624-6. CrossrefMedlineGoogle Scholar3. GLEESONGRAVES MP. Complications of dietary deficiency of vitamin B12 in young caucasians. Postgrad Med J. 1974;50:462-4. CrossrefMedlineGoogle Scholar4. JADHAVWEBBVAISHNAVABAKER MJSS. Vitamin B12 deficiency in Indian infants. Lancet. 1962;2:903-7. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Fargo Clinic, Ltd. Fargo, ND 58123 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1981Volume 94, Issue 6Page: 823-824KeywordsCholesterolDietHematology and oncologyHygieneVitamin B12 deficiency Issue Published: 1 June 1981 PDF downloadLoading ...

Single nutrient deficiency and cell-mediated immune responses. II. Pyridoxine

Weanling rats given pyridoxine-deficient diet and 4-deoxypyridoxine hydrochloride in water showed a significant reduction in the weights of the thymus and the spleen as well as in the number of lymphocytes in these organs compared with values in pair-fed controls and animals fed ad libitum. The number of ‘background’ plaque forming cells in the spleen was increased but the number of post-immunization antibody-forming cells was reduced. Dose response curve for phytohemagglutinin-induced lymphocyte stimulation was significantly lower than in controls. Serum thymic hormone activity was decreased. These immunologic changes may result in altered vulnerability to infection.

Growth stimulating effect of picolinic acid added to rat diets.

Rats fed either a soybean protein-based diet or a casein-based diet supplemented with picolinic acid gained significantly more weight than rats fed unsupplemented diets. The zinc concentration of the kidneys from the rats fed the diets supplemented with picolinic acid was significantly greater than that of the rats fed the unsupplemented diets. Rats fed a pyridoxine-free diet formulated with vitamin-free casein and supplemented with picolinic acid gained significantly more weight than rats fed an unsupplemented pyridoxine-deficient diet. The zinc concentration of the kidneys from the rats fed the pyridoxine-deficient diet supplemented with picolinic acid was significantly greater than that of the rats fed the unsupplemented diet. Dietary zinc absorption and food efficiency were increased when rats were fed supplemental picolinic acid. The results suggest that picolinic acid may increase the bioavailability of dietary zinc and perhaps other divalent cations which results in increased food efficiency.