Xanthurenic Acid Excretion Research Articles

ビタミンB<SUB>6</SUB>代謝に関する研究

Kotake et al. observed that when tryptophan was given to rats fed on a high fat diet or administered with a large dose of various fatty acids, there was a remarkable increase in urinary xanthurenic acid excretion. Charconnet-Harding et al. also reported the increased excretion of some tryptophan metabolites including xanthurenic acid in the urine of rats fed on a vitamin B2 deficient diet. It was agreed in several workers that the abnormal increase of xanthurenic acid excretion in urine was due to vitamin B6 deficiency. Thus, a close relationship between the roles of vitamins B2 and B6 in tryptophan metabolism could be easily inferred. However, no definite explanation could be given to this metabolism.According to recent reports of Ichihara et al., in mammalian tissues pyridoxal phosphate is formed from pyridoxine via pyridoxine phosphate and pyridoxine phosphate oxidase is a flavoprotein.In the present works it was examined on the effect of a high fat diet and fatty acid administration on the activity of pyridoxine phosphate oxidase and other enzymes concerned with pyridoxal phosphate formation in rat liver in an effort to clarify the mechanism of the effect of fatty acids. The liver pyridoxal phosphate content and pyridoxine phosphate oxidase activity of rats fed on a high fat diet were determined weekly. They were found to decrease gradually. The change in pyridoxine phosphate oxidase activity seemed to precede that of the pyridoxal phosphate content. This suggests that pyridoxal phosphate formation decreased as a consequence of decreased pyridoxine phosphate oxidase activity. Those depressions both of liver pyridoxal phosphate content and the pyridoxine phosphate oxidase activity were prevented with FMN administration.Next, the liver pyridoxal phosphate content and pyridoxine phosphate oxidase activity of rats administered oral with various fatty acids were measured and also decreased.After oral administration of sodium butyrate, the variation of liver pyridoxal phosphate content and pyridoxine phosphate oxidase activity with time investigated, both indicated parallel variation and later returned to normal levels. As in the case of fat feeding, the effect of fatty acids administration was prevented with simultaneous injection of riboflavin.Also tne activity of xanthine oxidase, a flavine enzyme, was found to be depressed under similar conditions, futhermore addition of FAD in vitro restored the depressed xanthine oxidase activity. Those findings emphasize the fact that fatty acid administration causes a relative vitamin B2 deficiency.

Kynurenine-transaminase, kynureninase and the increase of xanthurenic acid excretion.

Journal Article Kynurenine-Transaminase, Kynureninase and the Increase of Xanthurenic Acid Excretion Get access NOBUAKI OGASAWARA, NOBUAKI OGASAWARA Laboratory of Nutrition, the Department of Public Health, Shool of Medicine, Nagoya UniversityNagoya Search for other works by this author on: Oxford Academic PubMed Google Scholar YASUMICHI HAGINO, YASUMICHI HAGINO Laboratory of Nutrition, the Department of Public Health, Shool of Medicine, Nagoya UniversityNagoya Search for other works by this author on: Oxford Academic PubMed Google Scholar YAHITO KOTAKE YAHITO KOTAKE Laboratory of Nutrition, the Department of Public Health, Shool of Medicine, Nagoya UniversityNagoya Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Biochemistry, Volume 52, Issue 3, September 1962, Pages 162–166, https://doi.org/10.1093/oxfordjournals.jbchem.a127591 Published: 01 September 1962 Article history Received: 31 March 1962 Published: 01 September 1962

Xanthurenic acid excretion studies in anemic and non-anemic carriers of the fish tapeworm.

Xanthurenic acid excretion studies in anemic and non-anemic carriers of the fish tapeworm.

The state of pyridoxine nutrition in patients with kwashiorkor

Various biochemical criteria were applied in a study of the state of pyridoxine nutrition in 18 patients with kwashiorkor. There was evidence of pyridoxine need in 4 patients who excreted large amounts of xanthurenic acid in the urine after a tryptophan load, and in 5 other patients who lost the ability to convert tryptophan to niacin. In all patients the amount of xanthurenic acid excreted in the urine decreased after parenteral administration of pyridoxine hydrochloride. The excretion of 4-pyridoxic acid was extremely low in all patients on admission to the hospital but increased gradually during dietary treatment, while a marked increase occurred after administration of pyridoxine hydrochloride. The other criteria used in this investigation (viz., total lymphocyte counts, glutamic oxalacetic transaminase activity of the serum) revealed no definite evidence of pyridoxine need. It is suggested that determination of urinary xanthurenic acid excretion, before and after a tryptophan load, should be used in future studies of the state of pyridoxine nutrition in patients with kwashiorkor. Various biochemical criteria were applied in a study of the state of pyridoxine nutrition in 18 patients with kwashiorkor. There was evidence of pyridoxine need in 4 patients who excreted large amounts of xanthurenic acid in the urine after a tryptophan load, and in 5 other patients who lost the ability to convert tryptophan to niacin. In all patients the amount of xanthurenic acid excreted in the urine decreased after parenteral administration of pyridoxine hydrochloride. The excretion of 4-pyridoxic acid was extremely low in all patients on admission to the hospital but increased gradually during dietary treatment, while a marked increase occurred after administration of pyridoxine hydrochloride. The other criteria used in this investigation (viz., total lymphocyte counts, glutamic oxalacetic transaminase activity of the serum) revealed no definite evidence of pyridoxine need. It is suggested that determination of urinary xanthurenic acid excretion, before and after a tryptophan load, should be used in future studies of the state of pyridoxine nutrition in patients with kwashiorkor.

Pyridoxine-Responsive Anemia: Report of 2 Cases in Brothers and a Review of the Literature

Abstract The clinical and laboratory findings in two brothers with severe anemia are presented. These findings were very similar in both cases. Evidence that at least one of them suffered from a pyridoxine-responsive anemia is presented. It was assumed that the other had the same disorder since, in addition to the striking similarity in the clinical and laboratory abnormalities, the latter’s anemia disappeared completely with the parenteral administration of vitamin B complex, which provided him with 2 mg. of pyridoxine daily. These patients have not relapsed 1.5 and 6 years after stopping the therapy. A review of the reported cases with anemia responding to vitamin B6 administration is presented. Common factors observed in some of these cases are: (1) severe anemia, microcytic and hypochromic in type, chiefly due to a striking maturation erythroblastic arrest at the basophilic stage with no defect in leukocytes or thrombocytes; (2) hyperferremia and hemosiderosis; (3) an abnormal tryptophan-loading test; and (4) complete or almost complete correction of all abnormalities with administration of vitamin B6, even at small doses. These data were considered to suggest that the patients had a true deficiency in pyridoxine. In other patients, no increased excretion of xanthurenic acid has been observed after a tryptophan-loading dose, and pyridoxine administration has improved the anemia only partially and has not reversed the serum iron parameters to normality. All of these other patients suffered from a familial hypochromic anemia not due to iron deficiency or from a "sidero-achrestic" or "refractory normoblastic" anemia. The cause of the disorder in patients in the first group is unknown, but, by exclusion, increased requirement of vitamin B6 seems to be the most likely possibility.

Dietary Magnesium, Calcium, and Vitamin B6 and Experimental Nephropathies in Rats: Calcium Oxalate Calculi, Apatite Nephrocalcinosis

The effects of varying dietary levels of vitamin B6, magnesium and calcium were studied in rats, in terms of the urinary excretion of various metabolites and of the deposition in the urinary tract of calcium oxalate and apatite. Primary renal deposits of oxalate with secondary obstructive sequelae involving the lower urinary tract occurred in vitamin B6-deficient rats, accompanied by increased excretion of oxalic and xanthurenic acids and by a marked decrease in citric acid excretion. The feeding of diets high in magnesium (400 mg per 100 gm) markedly reduced the deposition of oxalate in vitamin B6-deficient rats although they remained hyperoxaluric. The urinary citrate, however, returned to normal levels or above, whereas the excretion of xanthurenic acid was lowered. The efficacy of high concentrations of dietary magnesium in decreasing renal oxalate deposition in vitamin B6 deficiency appeared related to change in the solvent characteristics of the urine. Varying the dietary calcium level from 0.2 to 1.2%, in conjunction with vitamin B6 deficiency, demonstrated a direct correlation between dietary calcium and the extent of oxalate deposition, an effect that became more pronounced when combined with low dietary magnesium. Distinct differences could be observed between two strains of white rats as to relative sensitivity to vitamin B6 deprivation, judged both by weight gain and extent of renal oxalate deposits. Renal deposition of apatite is correlated inversely with the dietary level of magnesium and directly with the level of dietary calcium. At the commonly used magnesium intake of 40 mg per 100 gm, such deposits were seen in minimal amounts in a quarter of the animals. At this magnesium concentration, deficiency of vitamin B6 protected the animals against apatite deposition. The magnesium requirement of weanling white rats, as judged by the occurrence of renal apatite deposits, would appear to be in excess of 40 mg per 100 gm.

Pyridoxine Deficiency in Hyperthyroidism.

SummaryThe occurrence of pyridoxine deficiency was determined in 14 patients with hyperthyroidism and 14 control euthyroid patients by the tryptophan load test. Urinary xanthurenic acid excretion following the tryptophan load test was significantly greater in hyperthyroid patients than in controls. Mean excretion of xanthurenic acid in hyperthyroid cases was 71.9 mg/24 hr with standard deviation of 56.0. Mean xanthurenic acid excretion of control cases was 15.4 with standard deviation of 6.1. After pyridoxine administration, mean xanthurenic acid excretion was 13.2 with standard deviation of 8.7 in the hyperthyroid cases, while in the control group, xanthurenic acid excretion was 12.5 with standard deviation of 5.2. Since pyridoxine is required for orderly catabolism of tryptophan and pyridoxine corrected this metabolic aberration, it is not unreasonable to state that in hyperthyroidism, the availability of pyridoxine is limited. Until the actual significance of these findings becomes more clearly defined...

Pyridoxine deficiency in congestive heart failure.

Summary1. Fourteen patients with congestive heart failure and 14 control patients without heart failure were studied with the tryptophan load test. 2. Urinary xanthurenic acid excretion following tryptophan load was significantly greater in the cardiac group than in controls. Mean XA excretion of the group with congestive failure was 35.6 mg/24 hours with standard deviation of 22.8. Mean excretion of the control group was 12.9 mg/24 hours with standard deviation of 5.2 mg/24 hours. 3. The heart failure group, which attained a higher level of XA excretion than the control group in the post tryptophan period, showed a greater decline in XA excretion after pyridoxine than the controls. 4. Since pyridoxine is required for orderly catabolism of tryptophan and pyridoxine corrects this metabolic aberration of tryptophan, it is not unreasonable to state that in congestive heart failure availability of Vit. B6 is limited.

Metabolic Studies of Mongoloids

The metabolism of a number of water-soluble vitamins by mongoloid and non-mongoloid, all mentally deficient children, has been studied. Relatively little differences in the excretion of thiamine, riboflavin, niacin, N-methylnicotinamide and vitamin C were observed prior to vitamin load tests. Following the load tests no significant difference was observed in the excretion of riboflavin by mongoloids and non-mongoloids and the excretion of thiamine although slightly greater in mongoloids was not marked. The administration of 100 mg of nicotinamide resulted in significantly less excretion of ɴ-methylnicotinamide and creatinine by mongoloids than non-mongoloids. The possibility of a defect in the methylating ability of mongoloids has been suggested. Following the feeding of 5 g of ᴅ ʟ-tryptophan, significant differences in $-methylnicotinamide and creatinine excretion were not observed, but the excretion of xanthurenic acid was lower in mongoloids than non-mongoloids.

Association of pyridoxine deficiency and convulsions in alcoholics.

Summary1. Increased xanthurenic acid excretion after 10 g dl-tryptophane was demonstrated in 3 of 5 patients with rum fits. This metabolic defect was corrected by Vit. B6 in a second tryptophane load test. 2. Patients with alcoholism and associated epilepsy, acute and chronic alcoholism, cirrhosis, acute hallucinosis-tremulousness, acute peripheral neuropathy, Wernicke-Korsakoff syndrome, and a non-alcoholic, healthy individual did not demonstrate significant Vit. B6 deficiency by this test. 3. It is postulated that Vit. B6 deficiency is etiologically related to rum fits.

A Study of Xanthurenic Acid Excretion by Swine1

A Study of Xanthurenic Acid Excretion by Swine1

Production of xanthurenic acid from tryptophan in pregnancy and in various states of nitrogen balance.

Production of xanthurenic acid from tryptophan was studied in pregnant women, in pregnant rats and in rats in vitamin B6 deficiency and various states of nitrogen balance. Of eight women well advanced in pregnancy only one excreted excessive xanthurenic acid after a test dose of tryptophan, and this pregnancy was complicated by disease. The excessive excretion in this case was reduced by dosage with pyridoxin. Rats late in pregnancy and early in the post-partum period typically excreted abnormally large amounts of xanthurenic acid after test doses of tryptophan. The administration of extra vitamin B6 or of other B vitamins had no effect. After the same level of dosage with tryptophan the excretion of xanthurenic acid by rats well advanced in vitamin B6 deficiency was much higher than that by pregnant rats. No conclusive evidence was obtained that the production of xanthurenic acid from tryptophan is associated with the state of nitrogen balance as influenced by pregnancy, vitamin B6 deficiency, or the intake of protein. Some of the experimental results suggested, however, that outside of vitamin B6 deficiency it tends to be high when the retention of nitrogen is high.

INTAKE OF VITAMIN B6 AND INFANTILE CONVULSIONS: A FIRST APPROXIMATION OF REQUIREMENTS OF PYRIDOXINE IN INFANTS

Nine infants, 1 to 12 months of age, with convulsions due to inapparent cause, have remained free of seizures after a change to a diet providing an increased amount of vitamin B6, or after administration of vitamin B6 as such. Five of these infants had been receiving a proprietary milk mixture found by analysis to be low in content of vitamin B6 (0.085 mg/l), two were breastfed and two, who developed convulsions in the neonatal period, had been receiving an evaporated milk mixture. Seven of the infants became free of convulsions when given an evaporated milk mixture supplying an average of 0.26 mg of vitamin B6 daily. Four of these seven infants were studied for biochemical evidence of deficiency of vitamin B6 by the use of a tryptophan loading test. All four excreted large amounts of xanthurenic acid after receiving 0.54 gm/kg of DL-tryptophan. One to 1.4 mg of vitamin B6 daily were required to prevent the excretion of xanthurenic acid. In contrast, 10 of 11 control infants receiving 0.2 to 0.5 mg of vitamin B6 daily failed to excrete xanthurenic acid when similarly tested and two of these infants, who began to excrete xanthurenic acid after receiving for 1 month a diet low in content of vitamin B6, ceased to do so after receiving 0.3 to 0.4 mg of vitamin B6 daily. This suggests that the requirement of vitamin B6 of the seven infants who had developed the deficiency is, for some reason greater than that of the average infant. The two infants whose convulsions appeared in the neonatal period required 2 to 5 mg of vitamin B6 daily to eliminate the seizures. One of these is still dependent upon a supplement of 2 mg of vitamin B6 daily. However, these two infants, like the control infants, required only 0.3 to 0.4 mg of vitamin B6 daily to prevent excretion of xanthurenic acid after receiving a dose of tryptophan. It seems probable that these two infants have anomalous metabolism of vitamin B6 rather than simple deficiency. In view of the above observations, it is recommended that an infant's diet contain 0.2 to 0.3 mg of vitamin B6 daily. However, since there are occasional instances of anomalous requirements, it is suggested that a therapeutic trial dose of 5 to 10 mg of pyridoxine hydrochloride daily be given to any infant with convulsions resulting from inapparent cause.

Evidence for Abnormal Vitamin B6Metabolism in Pregnancy and Various Disease States

Evidence for a biochemically demonstrable disturbance in the metabolism of vitamin B6during pregnancy is based on the following observations: (1) A marked increase of xanthurenic acid excretion following a tryptophan load test. (2) An abnormal excretion pattern of tryptophan metabolites on chromatographic analysis which is strikingly similar to that described in vitamin B6-deficient rats. (3) Immediate normalization of tryptophan metabolism following the administration of relatively small amounts of pyridoxine. (4) An abnormal vitamin B6, load test indicating a significantly larger retention of the administered vitamin in comparison to non-pregnant control subjects. Some patients with hyperthyroidism, febrile diseases, and carcinoma exhibit a similar disturbance of tryptophan metabolism which responds to the administration of pyridoxine. The possible mechanism of this disturbance is discussed and certain therapeutic implications are pointed out.

Metabolic interrelationships of vitamins E and B6.

SummaryRats deficient in both vit. E and B6 exhibited an increased excretion of allantoin and creatine and supplementation of the diet with either of these vitamins prevented this increase. Vit. B6 deficiency resulted in a decreased rate of growth and in the excretion of xanthurenic acid following tryptophan administration. Vit. E did not influence growth or xanthurenic acid excretion.

Xanthurenic acid excretion studies in diabetics with and without retinopathy.

Conclusions and Summary1. Diabetic patients with and without retinopathy excrete on the average significantly greater quantities of xanthurenic acid after an oral test load of 10 g dl-tryptophane than do non-diabetic controls. 2. There is no significant difference in the xanthurenic acid output of diabetic patients who have, and those who have not developed retinopathy.

Xanthurenic acid, an abnormal metabolite of tryptophan and the diabetic symptoms caused in albino rats by its production.

1. After administering tryptophan to albino rats fed on a B6 deficient diet containing casein, xanthurenic acid is excreted in the urine.2. Feeding rats on a diet containing much fatty acid salt and tryptophan, they become deficient in vitamin B6 and a remarkable amount of xanthurenic acid is excreted in the urine, which was isolated and identified. After the administration of pyridoxine, the urinary excretion of xanthurenic acid remarkably decreased but never completely disappeared.3. After administering orally both sodium butyrate and tryptophan to albino rats, the blood sugar curve show primary hyperglycemia, followed by temporary hypoglycemia, and finally definite hyperglycemia, accompanied by glycosuria owing to the production of xanthurenic acid.4. Administration of xanthurenic acid to albino rat leads also to the development of diabetic symptoms.5. Xanthurenic acid, when given continuously, shows an accumulative effect on diabetic symptoms. In the urine of the rats in hyperglycemia and vitamin B6 deficiency, a definite increase of acetone bodies is detected.6. The pancreas of rat showing hyperglycemia after feeding for a long period on high fat and casein diet or vitamin B6 deficient one, showed histologically degenerative changes of β-cells of Langerhans islets. It was especially conspicuous in vitamin B6 deficiency.7. In the urines of diabetic patients, the spot corresponding to free form of xanthurenic acid was detected by paper chromatography, contrary to the healthy subjects.8 Insulin was found to prevent the urinary excretion of xanthurenic acid of experimental animals as detected by paper chromatography. The product excreted in the urine instead of xanthurenic acid was proved to be kynurenic acid.9. Methionine inhibit the formation of xanthurenic acid. By simultaneous application of methionine and pyridoxine to rats, the urinary xanthurenic acid disappeared completely.10. The xanthurenic acid injected to rat is readily excreted in the urine. An enzyme, xanthurenicase, was found in rabbit liver.11. The injected xanthurenic acid is excreted in conjugated forms as non-toxic substances.

Studies on Chronic Vitamin B6 Deficiency in the Rat I. Changes in the Intact Animal

A vitamin B6 deficiency was produced in male albino rats by the use of the antivitamin, desoxypyridoxine, and a deficient diet. This was evidenced by the typical clinical signs of deficiency and an increased urinary excretion of xanthurenic acid. A significant increase in systolic blood pressure occurred in animals that were made deficient in vitamin B6 by either simple dietary depletion or the use of desoxypyridoxine. This elevation in blood pressure could be rapidly reduced to normal limits and the clinical signs of the deficiency reversed by the dietary use of pyridoxal hydrochloride. Old as well as young animals showed this pattern. Hematologic and histologic studies failed to reveal any significant changes, and in no case were vascular lesions demonstrated. The extracellular fluid volume of the deficient animals was well within the normal limits.

PYRIDOXINE DEPENDENCY: REPORT OF A CASE OF INTRACTABLE CONVULSIONS IN AN INFANT CONTROLLED BY PYRIDOXINE

A case of convulsions in an infant requiring pyridoxine for their control has been described. On oral dosage of pyridoxine 2 mg./day, seizures have now been controlled for 21 months, with no increase in dosage being required. A continuing need for pyridoxine is demonstrated by the recent reappearance of seizures following a short lapse of pyridoxine administration. In the absence of biochemical evidence of pyridoxine deficiency, as measured by xanthurenic acid excretion following a tryptophane load, and with meager clinical evidence for the complete picture of such deficiency, the authors prefer to designate this phenomenon "pyridoxine dependency" The hypothesis has been propounded that this infant suffers a metabolic anomaly in pyridoxine metabolism resulting in convulsions in the absence of regular dietary pyridoxine supplements.

A study of urinary excretion of xanthurenic acid and other tryptophan metabolites in human beings with pyridoxine deficiency induced by desoxypyridoxine

A study of urinary excretion of xanthurenic acid and other tryptophan metabolites in human beings with pyridoxine deficiency induced by desoxypyridoxine