TABLE 3

Comparison between the classic and the alternative pathways of BA synthesis

Classic (Neutral) PathwayAlternative (Acidic) Pathway
Operates in the liver.Initial steps involve many different cell types.
Initiated by cholesterol 7α-hydroxylase (CYP7A1).Initiated by sterol 27-hydroxylase (CYP27A1).
CYP7A1 is located in the hepatic endoplasmic reticulum.CYP27A1 is located in mitochondria of many different cell types.
CYP27A1–catalyzed oxidation is involved much later in the pathway.CYP27A1–catalyzed oxidation is involved at the very beginning of the pathway.
Modification of the sterol nucleus precedes the side chain oxidation.Side-chain oxidation precedes the modification of the sterol nucleus.
The classic pathway dominates in healthy humans, producing over 90% of the total BAs.The alternative pathway dominates in neonates. In adults, this pathway produces 5–10% of the total BAs.