Evidence for carrier proteins in bile acid synthesis. The effect of squalene and sterol carrier protein and albumin on the activity of 12alpha-hydroxylase.
The possibility that carrier proteins are involved in bile acid synthesis was investigated using rat liver homogenates. The 105 000 X g supernatant fraction was found to contain heat stable proteins that bound the bile acid precursor, 7alpha-hydroxy-4-cholesten-3-one, and increased the amount of 7alpha, 12alpha-dihydroxy-4-cholesten-3-one formed by the microsomal enzyme, 12alpha-hydroxylase. Subsequent studies were carried out to determine if squalene and sterol carrier protein or albumin, two lipid binding proteins present in the 105 00 X g supernatant fraction of rat liver homogenates, may be responsible for the effects seen with this fraction. Squalene and sterol carrier protein bound several water insoluble bile acid precursors, including 7alpha-hydroxy-4-cholesten-3-one, and increased the apparent activity of 12alpha-hydroxylase. Squalene and sterol carrier protein, however, did not bind either cholic acid or chenodeoxycholic acid. Rat serum albumin also bound 7alpha-hydroxy-4-cholesten-3-one and increased the apparent activity of 12alpha-hydroxylase. Kinetic analysis indicated that the apparent stimulation of 12alpha-hydroxylase by squalene and sterol carrier protein and albumin was due to increased solubilization of the substrate, 7alpha-hydroxy-4-cholesten-3-one. Thus, these studies indicate that bile acid precursor carrier proteins are present in the 105 000 Xg supernatant fraction of rat liver homogenates and suggest that squalene and sterol carrier protein or albumin may participate as carrier proteins in bile acid synthesis.
D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000502:physiology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D011485:Protein Binding; D051381:Rats; D012709:Serum Albumin / Q000502:physiology*; D013185:Squalene / Q000494:pharmacology*; D013250:Steroid Hydroxylases / Q000378:metabolism*; D013261:Sterols / Q000378:metabolism*; D013329:Structure-Activity Relationship
D002352:Carrier Proteins; D012709:Serum Albumin; D013261:Sterols; D013185:Squalene; D013250:Steroid Hydroxylases