B12 Cobalamins

Complexes of the composition RCo (dioximeH)2L (R = alkyl, L = neutral ligand) and their parent complexes with BR2 bridges RCo(dioxime-BR2)2L 127 (Fig. 33) are known as organocobaloximes [173-178] and have received attention being models for vitamin B12 (cobalamines) [183]. A series of related complexes of the composition Fe (dioxime-BR2)LL 128 (Fig. 33) without the metal-carbon bond is also known [179, 180]. 

There are many causes of the clinical condition referred to as anaemia. One particular type, whose cause can be traced to a genuine metabolic defect is megaloblastic anaemia and is due to a deficiency of the vitamins B12 (cobalamin) and/or folate. These vitamins are required for normal cell division in all tissues, but the rapid production of red cells makes them more susceptible to deficiency. In megaloblastic anaemia the blood haemoglobin concentration falls the synthesis of haem is not impaired. Examination of the blood reveals the appearance of larger then normal cells called macrocytes and megaloblasts are found in the bone marrow. 

Vitamin B12 (cobalamin 22) and fohc acid (23) are among the essential nutrients and are involved primarily as cofactors in metabolic functions as... 

Vitamin B12 (cobalamine) is one of the most complex low-molecular-weight substances occurring in nature. The core of the molecule consists of a tetrapyrrol system (corrin), with cobalt as the central atom (see p. 108). The vitamin is exclusively synthesized by microorganisms. It is abundant in liver, meat, eggs, and milk, but not in plant products. As the intestinal flora synthesize vitamin B12, strict vegetarians usually also have an adequate supply of the vitamin. 

Vitamin B12 (cobalamin) serves as a cofactor for several essential biochemical reactions in humans. Deficiency of vitamin B12 leads to megaloblastic anemia (Table 33-2), gastrointestinal symptoms, and neurologic abnormalities. Although... 

Elevated Hey levels can also occur in nutritional deficiencies of vitamin B12 (cobalamin) and folate. Folate or vitamin B12 deficiency can even lead to tHcy levels as high as those seen in the genetic homocystinurias [13]. In addition, a reciprocal relationship between blood levels or intake of these vitamins and tHcy concentrations... 

Propionyl-CoA is first carboxylated to form the d stereoisomer of methylmalonyl-CoA (Pig. 17—11) by propionyl-CoA carboxylase, which contains the cofactor biotin. In this enzymatic reaction, as in the pyruvate carboxylase reaction (see Pig. 16-16), C02 (or its hydrated ion, HCO ) is activated by attachment to biotin before its transfer to the substrate, in this case the propionate moiety. Formation of the carboxybiotin intermediate requires energy, which is provided by the cleavage of ATP to ADP and Pi- The D-methylmalonyl-CoA thus formed is enzymatically epimerized to its l stereoisomer by methylmalonyl-CoA epimerase (Pig. 17-11). The L-methylmal onyl -CoA then undergoes an intramolecular rearrangement to form succinyl-CoA, which can enter the citric acid cycle. This rearrangement is catalyzed by methylmalonyl-CoA mutase, which requires as its coenzyme 5 -deoxyadenosyl-cobalamin, or coenzyme Bi2, which is derived from vitamin B12 (cobalamin). Box 17—2 describes the role of coenzyme B12 in this remarkable exchange reaction. 

Vitamins B6, B12, and folate An elevated plasma homocysteine level is associated with increased cardiovascular risk (see p. 263). Homocysteine, which is thought to be toxic to the vascular endothelium, is converted into harmless amino acids by the action of enzymes that require the B vitamins—folate, B6 (pyridoxine), and B12 (cobalamin). Ingesting foods rich in these vitamins can lower homocysteine levels and possibly decrease the risk of car diovascular disease. Folate and B6 are found in leafy green veg etables, whole grains, some fruits, and fortified breakfast cereals. B12 comes from animal food, for example, meat, fish, and eggs. 

Vitamin B12 Cobalamin Methylcobalamin Deoxyadenosyl cobalamin Cofactor for reactions Homocysteine > Methionine I Methylmalonyl CoA -> Succinyl CoA j... 

Vitamin B12 (cobalamin) has as its active forms, methylcobalamin and deoxyadenosyl cobalamin. It serves as a cofactor for the conversion of homocysteine to methionine, and methylmalonyl CoA to succinyl CoA. A deficiency of cobalamin results in pernicious (megaloblastic) anemia, dementia, and spinal degeneration. The anemia is treated with IM or high oral doses of vitamin B12. There is no known toxicity for this vitamin. 

The major vitamins are described in separate alphabetical entries in tins book. Titles used for these entries have been selected on tlie basis of the most frequently used designations as of tlie early 1980s. In alphabetical order, the vitamins described in this book are Ascorbic Acid (Vitamin C) Biotin Choline and Cholinesterase Folic Acid Inositol Niacin Pantothenic Acid Vitamin Bj (Riboflavin) Thiamine (Vitamin Bj) Vitamin A Vitamin B (Pyridoxine) Vitamin B12 (Cobalamin) Vitamin D Vitamin E and Vitamin K. 

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. 

Vitamin B12 [cobalamin) Men women 2.4 pg/d Coenzyme in nucleic acid metabolism prevents mega-loblastic/pernicious anemia No adverse effects have been reported ... 

Vitamin B12 (cobalamins) (Figure 2.29) are extremely complex structures based on a corrin ring, which, although similar to the porphyrin ring found in haem, chlorophyll, and cytochromes,... 

Chronic nitrous oxide abuse can remove a lot of vitamin B12 from the bloodstream. B12 (cobalamin) is necessary for the creation of blood cells and neurotransmitters, as well as the protective layers that cover nerves. This results in nerve damage and pain balancing, walking, and concentration difficulties mental impairment mood disturbances (such as depression) and other physical problems. Chronic nitrous oxide use may also interfere with the production in bone marrow of white blood cells and red blood cells. Treatment with intramuscular injections of B12 may reverse these symptoms. 

Vitamin Ka Niacin3 Pantothenic acida Riboflavin3 Thiamin Pyridoxine B12 (cobalamin)3 Vitamin C (ascorbic acid)... 

Figure 28-2. The structure of vitamin B12 (cobalamin). Vitamin B12 is composed of a planar corrin ring containing a cobalt atom at the center. The corrin ring system is composed of four pyrrole rings and is similar to porphyrin in heme. The cobalt atom is coordinated to the nitrogens of each pyrrole ring and to a dimethylbenzimidazole group. The R group attached to the sixth coordination site of the cobalt atom in vitamin B12 can be a -CN, -OH, -CH3, or adenosyl group.

Vitamin B12, cobalamin or cyanocobaltamin, C63H88CoN14Oi4P, has the most complicated structure of the B vitamins. It contains one atom of cobalt in its molecule. It is required in minute amounts but without it the manufacture of proteins and red blood cells is affected. A diet which is deficient in liver, eggs, meat, fish or milk can lead to pernicious anaemia. Vegetarians are often advised to take vitamin B12 supplements. 

Marsh EN (1999) Coenzyme B12 (cobalamin)-dependent enzymes. Essays in Biochemistry 34, 139-54. 

Scalabrino G, Tredici G, Buccellato FR, and Manfndi A (2000) Further evidence for the involvement of epidermal growth factor in the signahngpathway of vitamin B12 (cobalamin) in the rat central nervous system. Journal of Neuropathology and Experimental Neurology 59, 808-14. 

Herbert, V, Fong, W., Guile, V, and Stopler, T. (1990). Low holotranscobalamin II is the earliest serum marker for subnormal vitamin B12 (cobalamin) absorption in patients with AIDS. Am. J. Hematol. 34,132-139. 

The metals copper, chromium and cobalt also appear to be essential for growth for some, if not all, microorganisms. Cobalt is an essential requirement for cobalamin-utilizing bacteria, but apart from being an alternative substrate for an Mg " " transport system, there appears to be no highly specific transport system for Co. E. coli has a high affinity uptake system for cyanocobalamin, even though it does not require B12. Cobalamin may thus serve as a source of cobalt. 

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