Synthesis of bile acids and bile salts via 24-hydroxycholesterol

Stable Identifier
Homo sapiens
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In the body, 24-hydroxycholesterol is synthesized in the brain, exported to the liver, and converted there to bile acids and bile salts. This pathway is only a minor source of bile acids and bile salts, but appears to be critical for the disposal of excess cholesterol from the brain (Bjorkhem et al. 1998; Javitt 2002).

In the liver, conversion of 24-hydroxycholesterol to bile acids and bile salts is initiated with hydroxylation and oxidoreductase reactions to form 4-cholesten-7alpha,24(S)-diol-3-one. The pathway then branches: hydroxylation of 4-cholesten-7alpha,24(S)-diol-3-one to 4-cholesten-7alpha,12alpha,24(S)-triol-3-one leads ultimately to the formation of cholate, while its reduction to 5beta-cholestan-7alpha,24(S)-diol-3-one leads to chenodeoxycholate formation. In both branches, reactions in the cytosol, the mitochondrial matrix, and the peroxisomal matrix result in modifications to the ring structure, shortening and oxidation of the side chain, conversion to a Coenzyme A derivative, and conjugation with the amino acids glycine or taurine (Russell 2003). These reactions are outlined in the figure below. The final three reactions are identical to ones of bile salt synthesis initiated by 7alpha-hydroxylation and are shown as arrows with no substrates.

Literature References
PubMed ID Title Journal Year
11969205 Cholesterol, hydroxycholesterols, and bile acids

Javitt, NB

Biochem Biophys Res Commun 2002
12543708 The enzymes, regulation, and genetics of bile acid synthesis

Russell, DW

Annu Rev Biochem 2003
9717719 Cholesterol homeostasis in human brain: turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation

Lutjohann, D, Bjorkhem, I, Diczfalusy, U, Stahle, L, Ahlborg, G, Wahren, J

J Lipid Res 1998
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