A comparative study of the rate-limiting enzymes of cholesterol synthesis, esterification and catabolism in the rat and rabbit.
1. The rat and rabbit are amongst the animal models most widely used in the study of human atherosclerosis, a disease state correlating with disturbances in cholesterol metabolism. 2. In order to relate the key regulatory enzymes of cholesterol synthesis, esterification and catabolism in the rat and rabbit to their differing degree of susceptibility to atherosclerosis, enzyme levels and their properties were determined in liver and intestine of both species. 3. Hepatic HMG CoA reductase and cholesterol 7 alpha-hydroxylase levels were significantly higher in the rat than in the rabbit, while intestinal HMG CoA reductase activity in the two species was comparable. Conversely, the capacity to esterify cholesterol as measured by ACAT activities was considerably greater in both sites in the rabbit compared to the rat. 4. The data suggest that differences in the key regulatory enzymes of cholesterol metabolism in both liver and intestine may reflect different methods of cholesterol utilization in the two species.
Devery
R A
RA
Department of Biochemistry, Royal College of Surgeons in Ireland, Dublin.
O'Meara
N
N
Collins
P B
PB
Johnson
A H
AH
Scott
L
L
Tomkin
G H
GH
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008798:Mevalonic Acid / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D011817:Rabbits / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains / Q000378:metabolism*; D013045:Species Specificity; D013250:Steroid Hydroxylases / Q000378:metabolism*; D002785:Sterol O-Acyltransferase / Q000378:metabolism*
D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D013250:Steroid Hydroxylases; D002790:Cholesterol 7-alpha-Hydroxylase; D002785:Sterol O-Acyltransferase; D008798:Mevalonic Acid