Bile acids: Chemistry, physiology, and pathophysiology

Table 1 Minimum and maximum values of CMC in water at 37°C (in mmol/L) for the sodium salts of major bile acids

Bile acid	Minimum CMC	Maximum CMC
Cholic acid	2.5	29.3
Deoxycholic acid	0.8	70
Chenodeoxycholic acid	3.0	30
Taurocholic acid	1.5	12
Taurodeoxycholic acid	0.6	12
Taurochenodeoxycholic acid	1.25	8

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