Ontogeny and location of HMG-CoA reductase, ACAT, and MGAT in human small intestine.

Abstract

Because a few enzymes are in most tissues, enabling them to produce lipids necessary for growth and differentiation, the development of their activity in the intestine, an important organ of fat transport and metabolism, is of great interest. In this investigation, the ontogeny and location of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase (the key regulatory enzyme in the cholesterol pathway), acyl-CoA:cholesterol acyltransferase (ACAT; responsible for cholesterol esterification), and monoacylglycerol acyltransferase (MGAT; the more representative enzyme of the neutral lipid pathway) were examined in the human fetal small intestine. The developing gut exhibited high levels (pmol.mg-1.min-1) of HMG-CoA reductase (7.65 +/- 0.35), ACAT (16.98 +/- 1.12), and MGAT (689.74 +/- 37.54). Significant positive correlations were recorded between fetal age (8-22 wk) and the enzyme activities of HMG-CoA reductase in the proximal (P < 0.005) and middle (P < 0.01) segments, ACAT in the distal segment (P < 0.03), and MGAT in the proximal segment (P < 0.03) of the gut. Age-specific changes were found in the location of the three enzymes in the contiguous intestinal segments that were investigated. We concluded that the fetal small intestine has substantial HMG-CoA reductase, ACAT, and MGAT activity, which displays specific patterns during development.