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Further studies on the binding of vitamin B 12 to the cell wall of a B 12 -requiring Lactobacillus.

The vitamin B(12)-binding property of Lactobacillus leichmannii ATCC 7830 has been studied. The organism could bind 0.52 mug of B(12) per mg of cells. With regard to the cellular site for B(12) accumulation, three-quarters of the B(12) bound to the cell was found in the crude cell wall fraction, and the remaining one-quarter was found in the particulate (ribosome) fraction. After receiving enzymatic treatments with ribonuclease, lipase, and trypsin, the wall fraction retained three-fifths of the initial B(12). The possibility of cross-contamination of the wall and particulate fractions was excluded by measuring the contents of ribonucleic acid and hexosamines in each fraction. The B(12)-binding activity of the wall was destroyed by pretreatment of the wall with pepsin, Pronase, or trypsin. However, once bound to the wall, the B(12) was not released by the same treatments. These facts suggest that B(12) is bound to a polypeptide in the wall on which these enzymes act and that, once bound, B(12) somehow inhibits the enzymatic actions as described earlier with L. delbrueckii no. 1. A B(12)-polypeptide complex was isolated by treatment with 0.2 n HCl from walls to which B(12) had been bound. The complex was then purified. The complex moves as a single band on polyacrylamide gel electrophoresis. Its molecular weight was estimated around 21,500 with microheterogeneity on a Sephadex G-75 column. The mode of B(12) binding was found to be similar to that of L. delbrueckii.

Binding Sites↗

The association of vitamin b 12 and folate blood levels with mortality and cardiovascular morbidity incidence in the old old: the Bronx aging study.

OBJECTIVE: An elevated homocysteine level in the blood has been identified as an independent risk factor for vascular disease, including coronary atherosclerosis and venoembolic disease. A deficiency of vitamins B ( 6 ), B ( 12 ), or folate in the blood can cause increased blood levels of homocysteine. We set out to determine whether there was a relationship between blood levels of folate and B ( 12 ) and the subsequent development of cardiovascular disease and mortality in old old ambulatory men and women. DESIGN: Four hundred forty subjects (mean age, 79 years; 64% female) were followed in the Bronx Longitudinal Aging Study, a prospective study of 10 years duration, designed to assess risk factors for cardiovascular and cerebrovascular diseases and dementia in an ambulatory old old cohort. METHODS: Serum levels of vitamin B ( 12 ) and folate were measured and related to the incidence of total all-cause mortality, stroke, myocardial infarction, coronary heart disease, and cardiovascular disease. RESULTS: No statistical gender- or age-related differences were found in the mean levels of folate or B ( 12 ). The concentration of folate in the blood was not related to the incidence of mortality, myocardial infarction, stroke, or overall cardiovascular disease. However, by logistical regression and Cox proportional-hazards regression analyses, there was an increased incidence of mortality and coronary heart disease in those subjects having increased vitamin B ( 12 ) levels in the blood. Each 100-pg increase in B ( 12 ) was associated with a 10% increase in mortality and coronary heart disease incidence. CONCLUSION: These results suggest that in elderly subjects, vitamin B ( 12 ) supplementation should not be routinely provided unless there are clear indications for doing so (a deficiency state), and then only to replace enough B ( 12 ) to correct the deficiency. A suggested treatment paradigm is provided for managing vitamin deficiency states and hyperhomocysteinemia in elderly subjects.

Aged↗

Biosynthesis of cobalamin (vitamin B(12)).

The biosynthesis of vitamin B(12) is summarized, emphasizing the differences observed between the aerobic and anaerobic pathways. The biosynthetic route to adenosylcobalamin from its five-carbon precursor, 5-aminolaevulinic acid, can be divided into three sections: (1) the biosynthesis of uroporphyrinogen III from 5-aminolaevulinic acid, which is common to both pathways; (2) the conversion of uroporphyrinogen III into the ring-contracted, deacylated intermediate precorrin 6 or cobalt-precorrin 6, which includes the primary differences between the two pathways; and (3) the transformation of this intermediate to form adenosylcobalamin.

Aminolevulinic Acid↗

[Neuropsychological disorders in vitamin B 12 deficiency].

Vitamin B12 deficiency is often attended by neuropsychic disorders. In the geriatric population, the level of vitamin B12 is mostly reduced. However, the clinical manifestations and pathogenesis are not completely specified. The authors describe a female patients in whom vitamin B12 deficiency was coupled with manifest neuropsychic disorders. Provide a detailed depiction of the clinical status, the disease course and laboratory findings. Relate the most typical neuropsychic manifestations of vitamin B12 deficiency.

Ataxia↗

[Folic acid and vitamin B 12 in chronic alcoholics].

In 64 chronic alcoholics folic acid and vitamin B12 in plasma and folic acid in erythrocytes were determined. The mean values of folic acid in plasma and in erythrocytes were significantly below normal. The determination of vitamin B12 showed normal results in a group of 20 cases treated with vitamin B12 containing drugs, whereas in the group of untreated alcoholics significantly reduced values were found. Comparison of folic acid and vitamin B12 concentrations in plasma revealed a more frequent deficiency of folic acid than of vitamin B12, which was combined with anemia in half the alcoholics investigated. The need to treat chronic alcoholics with folic acid and vitamin B12 is pointed out.

Adult↗

Serum C3 content in vitamin B(12)-deficient rats.

As a clue to clarifying the role of vitamin B12 (B12) in the function of the complement system, serum C3 content was determined in B12-deficient rats, and the effect of the administration of methylcobalamin (CH3-B12) on the serum C3 content was also studied. It was found that the serum C3 content in rats fed on a vitamin B12-deficient diet for 90 and 120 days significantly decreased compared with that in control rats. The administration of CH3-B12) restored the serum C3 content to control levels. The above results indicate that B12-deficiency depressed the serum C3 content and lowered humoral immunocompetence, and that these changes were ascribable to B12-deficiency.

Animals↗

[Vitamin B 12 deficiency: early diagnosis in ambulatory care medicine].

Many patients suffer from vitamin B12 deficiency and are thus exposed to irreversible sequelae if diagnosis occurs at a late stage. This prospective study undertaken by eight practitioners over a period of 12 months concerns early diagnosis. Blood vitamin B12 levels were measured in 152 patients presenting macrocytosis detected by systematic MCV analysis at the time of a blood test, a neuropathy or a recent cognitive, affective and behavioural problem, and were found to be lowered (< or = 175 pmol/l) in 54 patients of whom 43 had undergone vitamin B12 test treatment for 6 months. Haematological, neurological and psychiatric evaluation was carried out before and after treatment, and a diagnosis of deficiency was recorded in 24 patients based on unequivocal response to therapy. Improvement was greatest haematologically in 12 patients, neurologically in 6 patients and psychiatrically in 6 other patients, with 4 patients showing a combination of all modes. These 24 patients (mean age 69 years) suffered from numerous pathologies which were liable to complicate diagnosis in some of them: neurological (46%), psychiatric (37%), chronic alcoholism (33%), folic acid deficiency (29%), and diabetes (17%). The only diagnostic element used as a criterion of deficiency was an extremely low level of vitamin B12 (< or = 75 pmol/l). Marked macrocytosis or a combination of haematological and neuropsychiatric signs are strong indicators, but only improvement under treatment allowed a diagnosis to be made in the majority of patients. Macrocytosis was, however, not present in 6 of the 12 neuropsychiatric patients. The study thus identified a high proportion of patients with vitamin B12 deficiency who additionally presented, in equal proportions, both haematological and neuropsychiatric symptoms. Neither the clinical examination nor the vitamin B12 level in general permit early diagnosis based on a high probability index and long-term follow-up. Simpler methods for early diagnosis are therefore needed.

Aged↗

Mechanisms of vitamin B(12) absorption in breast-fed infants.

OBJECTIVES: The mechanisms of vitamin B(12) absorption in infants are unknown. We investigated whether haptocorrin (HC), a vitamin B(12) -binding protein in human milk, facilitates vitamin B(12) absorption during the neonatal period or if it occurs by a process similar to that in adults involving another vitamin B(12) -binding protein, intrinsic factor (IF). METHODS: To determine whether HC or IF can deliver vitamin B(12) to the enterocyte, binding studies using Caco-2 intestinal cells in culture and purified human milk HC-[ (57)Co]vitamin B(12) or [(125)I]IF-vitamin B(12) were performed. Determination of IF secretion by infant stomach was investigated by a competitive ELISA on fecal extracts from breast-fed infants. Determination of receptors specific for IF-vitamin B(12) or HC-vitamin B(12) in infant intestine was achieved by ligand blot analysis using isolated brush border membrane vesicles (BBMV) from fetal and adult intestine and Caco-2 cells. PCR was performed to identify the IF receptor gene transcript in Caco-2 cells and fetal intestine. RESULTS: Limited binding of both HC and IF to Caco-2 cells was observed; however, HC displayed affinity to low molecular weight proteins in BBMV from fetal intestine and Caco-2 cells while IF showed affinity for a 240 kDa protein in BBMV from fetal intestine and Caco-2 cells. IF receptor gene transcript was identified in fetal intestine and Caco-2 cells. An increase in IF excretion from breast-fed infants throughout early life was observed. CONCLUSIONS: An IF-dependent vitamin B(12) absorption mechanism appears to be in place in breast-fed infants. However, IF levels may be too low in early life to participate in vitamin B(12) absorption; therefore, haptocorrin may mediate vitamin B(12) absorption until the absorption function can be taken over by a more mature IF system.

Asialoglycoprotein Receptor↗

[Radioanalytical methods of determination in vitro of folates and vitamin B 12: diagnostic use in disorders of absorption and utilization].

The blood concentrations of vitamin B12 and folate, which are very useful in diagnosis of megaloblastic anemia and of these factors' dificiencies, are actually measured by precise, rapid, and specific competitive binding radioassays. Futher clinical advantages can be reached with the application of other in vitro radioisotope techniques, such as radioassay of IF, of antibodies anti-IF, of transcobalamins, and of FABP (folic acid binding protein). The major impact of the vitamin B12, folates and other related radioassays has been to permit more Hospitals and laboratories to do these determinations, replacing the more time-consuming, relatively imprecise, and often artifactual microbiological assays.

Anemia, Megaloblastic↗

[The vitamin B 12 serum level at various ages].

A report is presented on the determination of the vitamin B12 content by means of radioassay in the serum of 402 healthy persons aged between 14 to 98 years. With increasing age a significant decrease of the vitamin B12 content could be observed in both sexes after the sixtieth year of age. In the age group between 21 to 30 only the low values of women made an exception, which may be due to the administration of contraceptives.

Adolescent↗

Plasma folate but not vitamin B(12) or homocysteine concentrations are reduced after short-term vitamin B(6) supplementation.

Adverse effects of high vitamin B(6) intake include peripheral neuropathy. Recent studies focussing on the reduction of plasma homocysteine as a risk factor for vascular disease showed that vitamin B(6) reduces plasma folate levels. The significance of this finding is unclear. We therefore analyzed plasma folate and basal homocysteine levels as well as the response to an oral methionine loading test in 8 healthy individuals before and after a controlled supplementation with oral doses of 25 mg pyridoxine for 10 days. Plasma pyridoxal phosphate increased from 40.6 +/- 13.6 to 426.8 +/- 200.3 nmol/l (p < 0.001), whereas plasma folate decreased from 6.3 +/- 1.6 to 4.6 +/-1.5 ng/ml (p < 0.01), respectively. Plasma vitamin B(12) and basal homocysteine levels remained unchanged (234.0 +/- 27.8 vs. 217.1 +/- 50.4 pg/ml and 10.9 +/- 4.8 vs. 10.1 +/- 3.6 micromol/l). There was no significant effect of vitamin B(6) supplementation on the area under methionine and homocysteine concentration versus time curve. Significant correlations were found between pre- and post-supplement levels of folate as well as PLP levels (r = 0.73, p < 0.05; r = 0.75, p < 0.05). These data suggest that a dose of 25 mg vitamin B(6) supplemented for 10 days reduces plasma folate but did not affect basal and postprandial homocysteine levels suggesting (1) a normal cellular availability of folate or (2) a compensation of impaired homocysteine remethylation by increased transsulfuration.

Adult↗

[Vitamin B 12 deficiency in strict vegetarian diet. Why do some people choose such a diet, and what will they do in case of vitamin B 12 deficiency].

Nine persons in the county of Troms, Norway, were interviewed on their strict vegetarian diet. Improved health was indicated as the main reason for their choice of diet, but religion was a contributing reason for some. Most of the study persons would increase the intake of vitamin B12 if a deficiency state were to occur. One person reported, however, that she would not regard vitamin B12 deficiency as a health problem. The interviews disclosed beliefs regarding human physiology that are very far removed from standard scientific knowledge. The article indicates that communication between patient and the health care system may be difficult in such circumstances. Problems of communication would probably be minimized if the patient had a thorough understanding of human physiology and the health worker a thorough understanding of the reasons for the patient's choice of diet.

Adult↗

[Vitamin B 12 levels in children with intestinal resection at the level of the ileum].

Serum concentration of vitamin B12 is reported in children who had previously lost partially or totally the ileum. Only one of them showed a definite pondostatural retardation when evaluation of growth and development was done. No evidence of anemia was found in any one of them and the estimation of vitamin B12 was abnormally low in only one case. Findings are discussed and the necessity to carry out a periodic control of vitamin B12 in children with ileal resection is stressed.

Adolescent↗