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Companion Animals: Vitamin B12

Functions

Vitamin B12 is an essential part of several enzyme systems that carry out a number of basic metabolic functions. Most reactions involve transfer or synthesis of one-carbon units, such as methyl groups. Vitamin B12 is metabolically related to other essential nutrients, such as choline, methionine and folic acid. (Savage and Lindenbaum, 1995). Although the most important tasks of vitamin B12 concern metabolism of nucleic acids and proteins, it also functions in metabolism of fats and carbohydrates. A summary of vitamin B12 functions includes (a) purine and pyrimidine synthesis, (b) transfer of methyl groups, (c) formation of proteins from amino acids and (d) carbohydrate and fat metabolism. General functions of vitamin B12 are to promote red blood cell synthesis and to maintain nervous system integrity, which are functions noticeably affected in the deficient state. Overall synthesis of protein is impaired in vitamin B12-deficient animals (Friesecke, 1980). Gluconeogenesis and hemopoiesis are critically affected by cobalt deficiency; and carbohydrate, lipid, and nucleic acid metabolism are all dependent on adequate B12 and folic acid metabolism.

Vitamin B12 is necessary in reduction of the one-carbon compounds of formate and formaldehyde, and in this way it participates with folic acid in biosynthesis of labile methyl groups. Formation of labile methyl groups is necessary for biosynthesis of purine and pyrimidine bases, which represent essential constituents of nucleic acids.

Deficiency of vitamin B12 will induce folic acid deficiency by blocking utilization of folic acid derivatives. An enzyme containing vitamin B12 removes the methyl group from methylfolate, thereby regenerating tetrahydrofolate (THF), used in producing the 5,20-methylene THF required for thymidylate synthesis.

In animal metabolism, propionate of dietary or metabolic origin is converted into succinate, which then enters the tricarboxylic acid (Krebs) cycle. Methylmalonyl-CoA isomerase (mutase) is a vitamin B12-requiring enzyme (5´-deoxyadenosylcobalamin) that catalyzes the conversion of methylmalonyl-CoA to succinyl-CoA. Flavin and Ochoa (1957) established that for succinate production the following steps are involved:

succinate production

Methylmalonyl-CoA (a) is an inactive isomer. Its active form, (b), is converted into succinyl-CoA by a methylmalonyl-CoA isomerase (methylmalonyl-CoA mutase) (fourth reaction).

Vitamin B12 is a metabolic essential for animal species studied, and vitamin B12 deficiency can be induced with the addition of high dietary levels of propionic acid. However, metabolism of propionic acid is of special interest in ruminant nutrition because large quantities are produced during carbohydrate fermentation in the rumen. Propionate production proceeds normally, but in cobalt or vitamin B12 deficiency, its rate of clearance from blood is depressed and methylmalonyl-CoA accumulates. This results in an increased urinary excretion of methylmalonic acid and also loss of appetite because impaired propionate metabolism leads to higher blood propionate levels, which are inversely correlated to voluntary feed intake (MacPherson, 1982).

 

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