Cobalamin metabolism

Patients typically present by 6-12 months with severe developmental retardation, convulsions, microcephaly and homocysteinemia (=50pmol/l) with hypomethioninemia (<20 pmol/1). A few individuals have had psychiatric disturbances. The blood concentration of vitamin B12 is normal, and, unlike individuals with defects of cobalamin metabolism, these patients manifest neither anemia nor methylmalonic aciduria. The blood folic acid level is usually low. 

A large elevation of Hey in body fluids and tissues is found in several genetic enzyme deficiencies, the homocystinurias. These include cystathionine /3-synlhase deficiency [9], the remethylation defects due to deficiency of MTHF reductase [10], methionine synthase and methionine synthase reductase deficiencies, as well as defects of intracellular cobalamin metabolism [11], namely the cblF, cblC and cblD defects. It is noteworthy that low levels of total Hey (tHcy) have been described in sulphite oxidase deficiency [12]. 

F Watanabe, Y Nakano. Comparative biochemistry of vitamin B12 (cobalamin) metabolism biochemical diversity in the systems for intracellular cobalamin transfer and synthesis of the coenzymes. Int J Biochem 23 1353-1359, 1991. 

K5. Kondo, H., Osborne, M. L., Kolhouse, J. F., Binder, M. J., Podell, E. R., Utley, C. S., Abrahams, R. S., and Allen, R. H., Nitrous oxide has multiple deleterious effects on cobalamin metabolism and causes decreases in activities of both mammalian Cobalamin-dependent enzymes in rats. J. Clin. Invest. 67, 1270-1283 (1981). 

Krungkrai, J., Webster, H. K., and Yuthavong, Y. (1990). Folate and cobalamin metabolism in Plasmodium falciparum. Parasitol. Today 6, 388-391. 

In the methionine cycle, cobalamin also plays a central role, as the methyl group of 5-methyltetrahydrofolate is first transferred to the cobalamin molecule and then further transferred to homocysteine to form methionine. This reaction explains the close connection of folate and cobalamin metabolism, as 5-methyltetrahydrofolate cannot be used for other reactions over than the methylation of homocysteine. Mild deficiency of folate and cobalamin is also associated with cognitive decline due to the neurotoxic effects of increased... 

Inborn errors of cobalamin metabolism are rare cobalamin C/D deficiency impairs the synthesis of methyl or adenosyl cobalamin, and can give rise to combined homocysteinuria and methylmalonic aciduria causing severe neurologic symptoms and epilepsy. Therapy with hydroxycobalamine and betaine is rarely successful. 

Table 7.2. Mechanisms of cobalamin metabolism disorders Cobalamin malabsorption Phase of absorption ...

Rollman N and Sjostrom G (1946) The behavior of some propionic acid bacteria strains against NaCl, NaN03, and heating. Svenska Mejerit 38(19) 199-201 (20) 209-212 Romanskaya NN, Diment GS and Vorobjeva LI (1985) Method of production of dairy beverages. Avt svidet No 1184506 Bull No 38 Rosenberg LE (1983) Disorders of propionate, methylmalonate and cobalamin metabolism. 

The methylmalonic acidemias [14, 15] are a family of disorders in the metaboUsm of branched-chain amino acids in which the activity of methyl-malonyl-CoA mutase is defective. They may be divided into mutase apoen-zyme defects and defects in cofactor synthesis or cobalamin metabolism. 

The former do not respond to vitamin B12 while the latter do. Among the defects in cobalamin metabolism, of four complementation groups two (cbLA and B) represent defects in the synthesis of deoxyadenosylcobalamin while the other two (cblC and D) represent a combined abnormality in which there is also defective synthesis of methylcobalamin, the cofactor for methionine synthesis [16]. 

Defective cobalamin metabolism leads to methylmalonic aciduria and homocystinuria (Cbl C). 

Specific treatment schedules are devised for patients with one of the various forms of congenital metabolic disturbance of cobalamin metabolism. In general these conditions require daily injections, sometimes in combination with folic acid, carnitine, betaine, or choline (50). 

Linnell et al. (85) and Dillon et al. (87) have analyzed the cobalamin distribution in the tissues of normal humans, pernicious anemia patients, and patients with various congenital disorders of cobalamin metabolism, using TLC with bioauto-graphic detection. The results for normal tissues, summarized in Table 5, show that AdoCbl is the most abundant cobalamin form, the concentration of MeCbl is quite variable, and CN-Cbl is hardly present except in blood cells. In pernicious... 

Further reading Rosenberg, L.E. (1978). Disorders of propionate, methylmalonate and cobalamin metabolism. In Stanbury, J.B.. Wyngaarden, J.B. and Fredrickson, D.S. (eds.) The Metabolic Basis of Inherited Disease. 4th Edn., p. 411. (New York McGraw-Hill)... 

Cobalamin metabolism in intact cells AdoCbl synthesis -... 

Willard, H.F., Ambani, L.M., Hart, A.C., Mahoney, M.J. and Rosenberg, L.E. (1976), Rapid prenatal and postnatal detection of inborn errors of propionate, methylmalonate, and cobalamin metabolism A sensitive assay using cultured cells. Hum. Genet., 34,277. 

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