Cyanocobalamin (Vitamin B12) is one
of a family of cobalamins consisting of 1) a corrin ring around
a cobalt atom and 2) a nucleotide group of a base (5,6-dimethylbenzimidazole)
and a phosphorylated ribose with 1-amino,2-propanol. This
complex is linked to a ß-group.
cyanide in cyanocobalamin (at right),
an adenosyl group in adenosylcobalamin,
a methyl group in methylcobalamin,
and a hydroxyl group in hydroxocobalamin.
Conversion between forms readily takes place in body tissues.
Cobalamin is synthesized exclusively by bacteria.
Cobalamin is temporarily bound to R-binding proteins, but
released by duodenal digestive enzymes. The newly freed cobalamin
is bound by intrinsic factor (IF) secreted by gastric
This IF-cobalamin complex binds to receptors on the
brush border of the ileal mucosa and is absorbed over a period
of several hours.
Most absorbed cobalamin (90%) is transfered to transcobalamin
II, the primary transport protein of cobalamin.
Total body stores of cobalamin measure 2-5 mg.
The average daily diet in the US contains about 5-30 mg,
where as daily requirements are only 2-5 mg/day.
Cobalamin, in the form of adenosylcobalamin, is stored primarily
in the liver.
Adenosylcobalamin is key to conversion of methylmalonyl CoA
to succinyl CoA (Krebs cycle).
Methylcobalamin is an essential part of the folate-cobalamin
reaction necessary for DNA synthesis.
Folic acid (pteroyl monoglutamic acid)
occurs in nature as relatively insoluble aggregates - polyglutamates.
Leafy vegetables (broccoli,spinach,asparagus,lettuce), fruit,
milk, eggs, liver, and yeast contain folic acid. Some intestinal
bacteria also form folic acid.
The average US diet contains about 1,000 mg
of folate. The daily requirement is 100-200 mg/day
and body stores average 5,000mg.
Additional folate is required during pregnancy and growth.
Liver is a major storage site, but releases folate only into
the bile for reaborption in the jejunum and ileum. This process,
refered to as the enterohepatic circulation, is necessary
for maintainance of plasma folate levels. Alcohol interferes
with the enterohepatic circulation of folate and can lower
plasma folate levels within hours.
Folate is absorbed in the proximal jejunum
and ileum although the mechanism is unclear. Conjugases along
the brush border break polyglutamates into monoglutamates
Folate circulates free or albumin bound in the plasma as
Absorbed N5-methyl FH4 hands off a methyl group to synthesize
methionine from homocysteine in a step requiring cobalamin
and generates FH4 (tetrahydrofolate) which is reconjugated
to N5,10-methylene FH4 or other FH4-(Glu)n for use in thymidilate
and purine synthesis.
Under no circumstances should you share any material downloaded from Student Source course websites with individuals outside the class. Under no circumstances should you repost material downloaded from Student Source to other websites. Some of our pages are restricted to UVa School of Medicine users and require an Oasis account for access.