Bile acids: Chemistry, physiology, and pathophysiology

Table 2 Inborn defects in bile acid synthesis and biotransformation

Impaired process	Defect localization	Consequences
Sterol ring modification	Cholesterol 7α-hydroxylase (CYP7A1)	Increased hepatic cholesterol. In adults, LDL hypercholesterolemia and cholesterol gallstones
	Oxysterol 7α-hydroxylase (CYP7B1)	Accumulation of monohydroxyl bile acid species with marked cholestatic and hepatotoxic capabilities. Severe neonatal liver disease
	3β-Hydroxy-C27-steroid dehydrogenase/somerase (HSD3B7)	Cholestatic jaundice and malabsorption of lipids and lipid-soluble vitamins
	δ-4-3-Oxosteroid 5β-reductase (AKR1D1)	Accumulation of δ-4-3-oxo- and allo(5α-H)-bile acids. Liver disease rapidly progressing to liver failure
Side-chain modification	27-Hydroxylase (CYP27A1)	Cerebrotendinous xanthomatosis
	25-Hydroxylase (CH25H)	Low levels of primary bile acids in serum and increased urinary excretion of typical bile alcohols
	α-Methylacyl-CoA racemase (AMACR)	High concentrations of (25R) trihydroxy-cholestanoic acid in urine, bile, and serum
	Complete or partial absence of peroxisomes	Zellweger syndrome
		Infantile Refsum disease
		Neonatal adrenoleukodystrophy
		Hyperpipecolic acidemia
	Altered peroxisomal enzymes	Pseudo-Zellweger syndrome
		Pseudo-neonatal adrenoleukodystrophy
		X-linked adrenoleukodystrophy
Bile acid amidation	Bile acid acyltransferase (BAAT)	Absence of taurine or glycine conjugates. Enhanced proportion of sulfate and glucuronide conjugates
	Bile acid-CoA ligase?	Absence of taurine or glycine conjugates. Enhanced proportion of sulfate and glucuronide conjugates