Page 323 - Color Atlas of Biochemistry

P. 323

314 Tissues and organs

Bile acids cleavage of the OH group at C-7 (see B).
They are therefore referred to as secondary
Bile is an important product released by the bile acids.
hepatocytes. It promotes the digestion of fats
from food by emulsifying them in the small
intestine (see p. 2770). The emulsifying com- B. Metabolism of bile salts
ponents of bile, apart from phospholipids, Bile salts are exclusively synthesized in the
mainly consist of bile acids and bile salts liver (see A). The slowest step in their biosyn-
(see below). The bile also contains free cho- thesis is hydroxylation at position 7 by a 7-D-
lesterol, which is excreted in this way (see hydroxylase. Cholic acid and other bile acids
p. 312). inhibit this reaction (end-product inhibition).
In this way, the bile acids present in the liver
regulate the rate of cholesterol utilization.
A. Bile acids and bile salts
Before leaving the liver, a large proportion
Bile acids are steroids consisting of 24 C atoms of thebileacids areactivated with CoAand
carrying one carboxylate group and several then conjugated with the amino acids glycine
hydroxyl groups. They are formed from cho- or taurine (2;cf. A). In this way, cholic acid
lesterol in the liver via an extensive reaction gives rise to glycocholic acid and taurocholic
pathway (top). Cytochrome P450 enzymes in acid. The liver bile secreted by the liver be-
the sER of hepatocytes are involved in many comes denser in the gallbladder as a result of
of the steps (seep. 318). Initially, the choles- the removal of water (bladder bile; 3).
terol double bond is removed. Monooxyge- Intestinal bacteria produce enzymes that
nases then introduce one or two additional can chemically alter the bile salts (4). The
OH groups into the sterane framework. Fi- acid amide bond in the bile salts is cleaved,
nally, the side chain is shortened by three C and dehydroxylation at C-7 yields the corre-
atoms, and the terminal C atom is oxidized to sponding secondary bile acids from the pri-
acarboxylate group. mary bile acids (5). Most of the intestinal bile
It is importantthatthe arrangementof the acids are resorbed again in the ileum (6)and
Aand Brings is altered from trans to cis dur- returned to the liver via the portal vein (en-
ing bile acid synthesis (see p. 54). The result terohepatic circulation). In the liver, the sec-
of this is that all of the hydrophilic groups in ondary bile acids give rise to primary bile
thebileacids lie on one side of the molecule. acids again, from which bile salts are again
Cholesterol, which is weakly amphipathic produced. Of the 15–30g bile salts that are
(top), has a small polar “head” and an ex- released with the bile per day, only around
tended apolar “tail.” By contrast, the much 0.5g therefore appears in the feces. This ap-
more strongly amphipathic bile acid mole- proximately corresponds to the amount of
cules (bottom) resemble disks with polar top daily de novo synthesis of cholesterol.
sides and apolar bottom sides. At physiolog-
ical pH values, the carboxyl groups are almost Further information
completely dissociated and therefore nega-
tively charged. Thecholesterol excreted with thebileis
Cholic acid and chenodeoxycholic acid, poorly water-soluble. Together with phos-
known as the primary bile acids,are quanti- pholipids and bile acids, it forms micelles
tatively the most important metabolites of (see p. 270), which keep it in solution. If the
cholesterol. After being biosynthesized, they proportions of phospholipids, bile acids and
are mostly activated with coenzyme A and cholesterol shift, gallstones can arise. These
then conjugated with glycine or the non-pro- mainly consist of precipitated cholesterol
teinogenic amino acid taurine (see p. 62). The (cholesterol stones), but can also contain
acid amides formed in this way are known as Ca 2+ salts of bile acids and bile pigments (pig-
conjugated bile acids or bile salts.They are ment stones).
even more amphipathic than the primary
products.
Deoxycholic acid and lithocholic acid are
only formed in the intestine by enzymatic

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