Plasma B12 Research Articles

Vitamin B6 Metabolism by Human Livera

The B6 vitamers (pyridoxine, pyridoxamine, and pyridoxal) are primarily metabolized in liver to pyridoxal 5'-phosphate (PLP) and the deadend catabolite 4-pyridoxic acid. We have built on the elegant early work of Snell and others to describe the activities of the human liver enzymes responsible for vitamin B6 metabolism and to develop a model of the relative rates of these interconversions in vivo. This model is consistent with changes in plasma B6 after a load, the clearance of different vitamers (e.g., pyridoxine versus pyridoxal), and with the low plasma PLP in patients with cirrhosis. Because cirrhotics were found to be capable of PLP synthesis, we have used oral supplementation with pyridoxine to restore plasma PLP to the normal range, and have evaluated the effects of this intervention on amino acid metabolism. No significant differences were observed in plasma or urinary clearance of methionine (or cystathionine) after an oral load, nor in amino acid clearance from circulation after a protein load for cirrhotic patients before and after restoration of normal plasma PLP. Hence, the abnormal metabolism of vitamin B6 does not appear to be an important factor in the deranged amino acid metabolism in this disease. Nonetheless, this approach may be generally useful in assessing the importance of PLP in other abnormalities.

Pharmacokinetic Properties of the Plasma B6 Vitamers after Single and Chronic Oral Pyridoxine Mega Doses

Annals of the New York Academy of SciencesVolume 585, Issue 1 p. 557-559 Pharmacokinetic Properties of the Plasma B6 Vitamers after Single and Chronic Oral Pyridoxine Mega Doses ANNETTE SPEITLING, Corresponding Author ANNETTE SPEITLING Institute of Nutrition University of Giessen Federal Republic of GermanyaAddress for correspondence: Institute of Nutrition, c/o Annette Speitling, Goethestr. 55, D-6300 Giessen, FRG.Search for more papers by this authorHELMUT HESEKER, HELMUT HESEKER Institute of Nutrition University of Giessen Federal Republic of GermanySearch for more papers by this authorWERNER KÜBLER, WERNER KÜBLER Institute of Nutrition University of Giessen Federal Republic of GermanySearch for more papers by this author ANNETTE SPEITLING, Corresponding Author ANNETTE SPEITLING Institute of Nutrition University of Giessen Federal Republic of GermanyaAddress for correspondence: Institute of Nutrition, c/o Annette Speitling, Goethestr. 55, D-6300 Giessen, FRG.Search for more papers by this authorHELMUT HESEKER, HELMUT HESEKER Institute of Nutrition University of Giessen Federal Republic of GermanySearch for more papers by this authorWERNER KÜBLER, WERNER KÜBLER Institute of Nutrition University of Giessen Federal Republic of GermanySearch for more papers by this author First published: May 1990 https://doi.org/10.1111/j.1749-6632.1990.tb28104.xCitations: 10AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume585, Issue1Vitamin B6May 1990Pages 557-559 RelatedInformation

Concentration of Vitamin B6 and Activities of Enzymes of B6 Metabolism in the Blood of Alcoholic and Nonalcoholic Men

The purpose of this study was to compare concentrations of vitamin B6 compounds and the activities of enzymes that synthesize or catabolize pyridoxal 5'-phosphate in the plasma and erythrocytes of nonalcoholic and alcoholic subjects. Blood was obtained from male nonalcoholics and chronic alcoholics with minimal liver damage and normal hematology. Plasma, erythrocyte, and urinary B6 compounds were analyzed by high performance liquid chromatography, and pyridoxal phosphate was also measured enzymatically. Erythrocyte pyridoxine kinase and pyridoxine phosphate oxidase and erythrocyte and plasma pyridoxine phosphate phosphatases were assayed. Plasma pyridoxal phosphate concentration was significantly lower in the alcoholics (31.3 +/- 3.6 nmol/liter) than in the nonalcoholics (58.7 +/- 7.5 nmol/liter). The concentrations of the other B6 compounds in plasma, erythrocytes, and urine were not different in the two groups. Plasma alkaline pyridoxine phosphate phosphatase activity was significantly higher in the alcoholics (4.05 +/- 0.36 nmol/(h.mg] than in the nonalcoholics (3.01 +/- 0.18 nmol/(h.mg]. The activities of erythrocyte kinase, oxidase, and phosphatases were not significantly different in the two groups. The relationship of plasma pyridoxal phosphate concentration to its metabolites and the activities of the enzymes involved in its metabolism was determined. Plasma pyridoxine phosphate phosphatase activity assayed at pH 9.0 or 7.4 correlated negatively with plasma pyridoxal phosphate concentration. The low pyridoxal phosphate concentration observed in the plasma of the alcoholic subjects may in part be related to increased plasma phosphatase activity.

611 Effect of nicotine and cigarette smoke on theophylline levels and plasma B6 in healthy rabbits

611 Effect of nicotine and cigarette smoke on theophylline levels and plasma B6 in healthy rabbits

PLASMA VITAMIN B 12 TITRES AS INDICATORS OF DISEASE SEVERITY AND MORTALITY OF PATIENTS WITH ALCOHOLIC HEPATITIS

Patients with alcoholic hepatitis with plasma B12 levels above 800 pg/ml have overt clinical manifestations of liver disease including severe hepatocellular damage. High plasma B12 levels significantly correlate (P less than 0.0001) with standard liver function tests, e.g. bilirubin, cholylglycine, alkaline phosphatase, AST and prothrombin time as an index of the severity of hepatic damage. Decrease in plasma B12 to normal titres implies a decrease in the severity of alcoholic liver disease, whereas increased plasma B12 levels relate to increased severity and mortality.

The plasma and red cell vitamin B levels of chronic hemodialysis patients: a longitudinal study.

Plasma B12, folate, B6 and thiamine, and red blood cell folate, thiamine and niacin levels were monitored for a period of 6 months in 15 clinically stable, chronic hemodialysis patients who were not supplemented with the water-soluble vitamins. Microbiological assays were used to determine the blood levels of the water-soluble vitamins. Over the period of 6 months, none of the patients had plasma or red cell vitamin levels below the normal range. No appreciable changes were observed in the plasma and red blood cell vitamin levels before and after dialysis in 5 patients. This study showed that chronic hemodialysis patients are able to maintain normal plasma and red cell levels of some water-soluble vitamins without daily supplementation.

Deranged Concentrations of Water-Soluble Vitamins in the Blood of Undialyzed and Dialyzed Patients with Chronic Renal Failure

Blood concentration of water-soluble vitamins were measured in patients with mild chronic renal insufficiency, uremic undialyzed and dialyzed patients and control subjects. The whole blood concentration of B1 was significantly lower in dialyzed patients. Plasma levels of B2 were elevated in uremic and dialyzed patients and plasma B6 was significantly increased in dialyzed patients. Serum levels of B12 and folic acid were elevated in uremic and dialyzed patients. The results of this study differ from those reported from Europe and the U.S.A. These geographical differences may arise primarily from differences in staple food, vegetable intake, and traditional methods of food preparation.

Provisional recommendation on the theory of reference values (1978): Part 1. The concept of reference values

By studying 516 healthy adults normal reference intervals were established for the Coulter “S” haematological indices with the plasma ferritin, B12, folate and red cell folate in a subgroup of 306. Significant sex related differences were found for all measurements other than MCV, MCH and B12. After allowing for these sex related differences, the effects of age, body size, fasting, smoking, alcohol, exercise and contraceptive pill usage on the parameters studied was defined.

Determination of erythrocyte vitamin B12 activity

Data presented in this paper show that there is no significant difference between plasma and serum vitam B12 activity when EDTA is used as the anticoagulant. By drawing 5 ml of blood into a tube containing EDTA, the whole blood and plasma B12 activity can be measured using Lactobacillus leichmannii for the assay as the test organism. Erythrocyte B12 levels can be obtained by difference after correcting for hematocrit. Sodium heparin appears to inhibit the growth of L. leichmannii.

The Failure of Granulocytes to Produce Transcobalamin I (TC I)

The hypothesis that transcobalamin I (TC I) originates from granulocytes was tested by comparing the isoelectric focusing (IEF) patterns of the R-type binder (cobalophilin) of vitamin B12 of: 1) lysed granulocytes, 2) 24 h granulocyte output, and 3) plasma. The preparations came from the blood of 5 normal subjects and 4 with myeloproliferative states. The cobalophilin released into a culture of granulocytes resembled the binder in the granulocytes initially. TC I, defined as the alpha1 cobalophilin with components isoelectric between pH 2.9-3.35 and as a carrier of native plasma B12, was not released by granulocytes. The granulocyte binder of leukaemic granulocytes did not differ from the normal in content per cell or amount released.

Transcobalamins I and II as natural transport proteins of vitamin B12.

There are two conflicting theories of how plasma vitamin B12 (B12) is transported in man: (a) by two distinct transport proteins, transcobalamins I and II (TC I and II), each having a specific role and time of function; and (b) by three active transport proteins, TC I, II, and III, that take up B12 randomly in proportion to the unsaturated amounts of each. To test these theories a man was given 1.12 mug, 229 muCi, of [57Co]B12 mixed with food. Blood samples were taken several times on the 1st day and at lengthening intervals up to day 51. The amount of TC II-B12 was measured in each sample by: gel filtration and by precipitation with (NH4)2SO4. Total serum R-B12 was then separated into TC I and TC III by: (a) a single step anion exchange system and (b) isoelectric focusing (IEF). As the B12 was being absorbed, 92-95% of that in venous blood was carried by TC II. Absolute and percentage transport by TC II declined sharply during the first 24 h; between days 7 and 51 20-33% of the label was on TC II, and the rest was carried by R-type binders. Absolute transport by TC I did not reach a maximum until after day 1 and before day 3. Transport by an alpha2 R-type binder, TC III, could not be demonstrated. TC I was isoelectrically heterogenous, with the components focusing between pH 2.9 and 3.35. It was concluded that (a) TC II is the dominant carrier of B12 immediately after absorption; (b) maximum transport by TC I requires the passage of time after absorption; (c) after the absorbed B12 reaches equilibrium with the total body B12, about one fourth of the plasma B12 is carried by TC II and three fourth by TC I; and (d) TC I and TC II are the only functional transport proteins of plasma B12.

Effect of Folic Acid on Amino Acid Metabolism in Pyridoxine Unresponsive Homocystinurics

Plasma folate levels were measured in 3 homocystinurics and found to be <1 ng/ml (normal 5–10 ng/ml). All were on unrestricted, constant protein diets while 2 (A and B) were taking anticonvulsants for seizure control. Patient A had anemia (8.0 G% hemoglobin) and macrocytosis that responded to folic acid. B had macrocytosis but no anemia while C had neither. Plasma folate levels ranged from 14–20 ng/ml after therapy. Within 3 months of discontinuing folic acid in B and C their blood folates had fallen to 2.0 and 2.6 ng/ml. Plasma B12 levels and excretion of methyl-malonate were normal. Plasma and urine amino acids responded to folic acid as noted in the table: Methylation of homocystine to methionine requires folic acid. Many homocystinurics may increase methylation to methionine thereby requiring more folate and increasing glycine as a result of demethylation of serine. Some homocystinurics may require long-term folic acid supplementation (A and B) whereas others are unresponsive either biochemically or hematologically (C). (Supported in part by USPHS grants AM-02231 and HD-04837.)

Tissue Distribution of Radio-B after Intravenous Injection of Gastric Juice, Saliva and Plasma-Bound Co 57 B12: I. In Man

Abstract Co57B12 bound to pernicious anemia gastric juice was administered intravenously to 4 normal individuals, and Co57B12 bound to autologous plasma was administered to 2 of these. Hepatic, arm and blood radioactivity were measured for one week and compared with that following the intravenous injection of unbound Co57B12. Pernicious anemia gastric juice increased hepatic uptake, delayed blood clearance and decreased arm uptake of Co57B12 as compared with Co57B12 injected unbound or bound to plasma. Thus, the B12 bound to gastric juice is retained longer in the intravascular space with greater uptake by liver. These results suggest that gastric juice B12 binders, but not plasma B12 binders, enhance hepatic B12 uptake either by acting at specific receptor sites on the liver cell membrane or by retaining B12 longer in circulation. This property of gastric juice B12 binders is not related to IF activity but is rather dependent upon some structural or functional feature common to both IF-related and nonrelated B12 binders of gastric juice.

Pyridoxal phosphate in plasma and leukocytes in patients with leukemia and other diseases.

SummaryThe amount of coenzymatically active Vit. B6 was determined in plasma and leukocytes in patients with various diseases. Values for plasma and leukocytes varied widely in all groups examined. A statistically significant decrease of plasma B6 was found only in patients with nutritional anemia and various forms of leukemia. However, the amount of pyridoxal phosphate was very low in individual patients with various other diseases. This may indicate a decreased intake of vitamin in some hospitalized patients or an increased need for it. B6 values in leukocytes were consistently decreased in patients with various forms of leukemia. In contrast, cells from normal bone marrow and from tonsils showed significantly higher amounts of pyridoxal phosphate. The findings are discussed with reference to a specific disturbance in B6 metabolism in some neoplastic conditions.

Pyridoxal Phosphate in Plasma and Leukocytes of Normal and Pregnant Subjects Following B6 Load Tests.

SummaryA method for determination of pyridoxal phosphate in human plasma is described. The amount of coenzymatically active form of Vit. B6 was determined simultaneously in blood of normal subjects, delivering women, and in cord blood of their babies. In general, amounts of pyridoxal phosphate in plasma and leukocytes showed parallel changes. They were low in maternal blood, and high in cord blood. Following oral administration of 100 mg pyridoxine hydrochloride, increases were observed in both plasma and leukocytic B6 values within a few hours. Considerably higher peaks were seen in normal controls as compared to women in last trimester of pregnancy and at time of delivery. The most significant difference between pregnant and nonpregnant subjects was noted in plasma values 24 hours following administration of vitamin. The possible practical application of these findings for evaluation of a latent B6 deficiency in clinical subjects is suggested.