Page 273 - Color_Atlas_of_Physiology_5th_Ed._-_A._Despopoulos_2003

Vitamin Absorption It takes years for these symptoms to manifest as the
body initially has a reserve of 1000 times the daily re-
Since higher animals cannot synthesize quirement of 1µg (! p. 90).
cobalamins (vitamin B 12), they must obtain Folic acid/folate (= pteroylglutamic acid). N , 5
this cobalt-containing coenzyme from the diet. N -methylenetetrahydrofolate, the metaboli-
10
Animal products (liver, kidneys, fish, eggs, cally active form of folic acid (daily require-
milk) are the main source. ment: 0.1–0.2 mg) is needed for DNA synthesis
(formation of deoxythymidylate from deoxy-
Cobalamin biochemistry. Aqua- and OH-cobalamin
are precursors of the two active forms, methyl- and uridylate). Folic acid in the diet usually occurs
adenosylcobalamin. Methylcobalamin is needed to in forms that contain up to seven glutamyl res-
form methionine from homocysteine; cobalamin idues (γ-linked peptide chain; Pte-Glu 7) in-
5
transfers the methyl group required for this from N - stead of pteroylglutamic acid (Pte-Glu 1). Since
Nutrition and Digestion bon–carbon bonds. tamyl chain must be shortened before absorp-
methyltetrahydrofolate (see below) to homocys-
only Pte-Glu 1 can be absorbed from the lumen
teine. Some enzymes, e.g. methyl-malonyl-CoA mu-
of the proximal jejunum (! B), its polyglu-
tase, need adenosylcobalamin to break and form car-
tion. This is done by pteroylpolyglutamate hy-
Cobalamins are relatively large and lipophobic
drolases located in the luminal membrane of
molecules that require transport proteins
enterocytes. The absorption of Pte-Glu 1 is me-
(! A). During passage through the GI tract,
diated by a specific active transporter. In mu-
bind to (1) intrinsic factor (IF), which is
5
yield N -methyltetrahydrofolate (5-Me-H 4-fo-
secreted by gastric parietal cells; (2) trans-
late) and other metabolites. If already present
10 plasma and other compartments, cobalamins cosal cells, Pte-Glu 1 is than broken down to
cobalamin II (TC II) in plasma; and (3) R proteins
in the ingested food, these metabolites are ab-
in plasma (TC I), and granulocytes (TC III), sorbed from the intestinal lumen by the afore-
saliva, bile, milk, etc. Gastric acid releases mentioned mechanism. (The same applies to
cobalamin from dietary proteins. In most the cytostatic drug, methotrexate.) Methyl-
cases, the cobalamin then binds to R protein in cobalamin is needed to convert 5-Me-H 4-folate
saliva or (if the pH is high) to IF (! A1). The to tetrahydrofolate (see above). The body
R protein is digested by trypsin in the stores about 7 mg of folic acid, enough for
duodenum, resulting in the release of several months (cf. folic acid deficiency,
cobalamin, which is then bound by (trypsin- ! p. 90).
resistant) intrinsic factor. The mucosa of the The other water-soluble vitamins—B 1 (thi-
terminal ileum has highly specific receptors for amin), B 2 (riboflavin), C (ascorbic acid), and H
the cobalamin-IF complex. IT binds to these re- (biotin, niacin)—are absorbed via Na symport
+
ceptors and is absorbed by receptor-mediated carriers (! C). Vitamin C is absorbed from the
endocytosis, provided a pH of ! 5.6 and Ca 2+ ileum, whereas vitamins B 1, B 2, and H are ab-
ions are available (! A2). The receptor density sorbed from the jejunum. Members of the vi-
and, thus, the absorption rate increases during tamin B 6 group (pyridoxal, pyridoxine, py-
pregnancy. Cobalamin binds to TC I, II and III in ridoxamine) are probably absorbed by passive
plasma (! A3). TC II mainly distributes mechanisms.
cobalamin to all cells undergoing division (TC Fat-soluble vitamins—A (retinol), D 3
II receptors, endocytosis). TC III (from granulo- (cholecalciferol), E (tocopherol), K 1 (phyl-
cytes) transports excess cobalamin and un- loquinone), and K 2 (menaquinone)—must be
wanted cobalamin derivatives to the liver (TC incorporated into micelles for absorption (cf.
III receptors), where it is either stored or ex- lipid digestion, p. 252). The exact absorption
creted in the bile. TC I has a half-life of roughly mechanism has not yet been explained,
10 days and serves as a short-term depot for though it is known to be partly saturation- and
cobalamin in the plasma. energy-dependent. Fat-soluble vitamins are
incorporated into chylomicrons and VLDL for
A vegan diet or disturbed cobalamin absorption can
260 lead to severe deficiency symptoms like pernicious transport in plasma (! p. 254ff.).
anemia and spinal cord damage (funicular myelosis).
Despopoulos, Color Atlas of Physiology © 2003 Thieme
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