ONTOGENY AND LOCATION OF HMG-COA REDUCTASE, ACAT, AND MGAT IN HUMAN SMALL-INTESTINE

Because a few enzymes are in most tissues, enabling them to produce li pids necessary for growth and differentiation, the development of thei r activity in the intestine, an important organ of fat transport and m etabolism, is of great interest. In this investigation, the ontogeny a nd location of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase (the key regulatory enzyme in the cholesterol pathway), acyl-CoA:cholester ol acyltransferase (ACAT; responsible for cholesterol esterification), and monoacylglycerol acyltransferase (MGAT; the more representative e nzyme of the neutral lipid pathway) were examined in the human fetal s mall 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 re corded between fetal age (8-22 wk) and the enzyme activities of HMG-Co A 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 segm ent (P < 0.03) of the gut. Age-specific changes were found in the loca tion of the three enzymes in the contiguous intestinal segments that w ere investigated. We concluded that the fetal small intestine has subs tantial HMG-CoA reductase, ACAT, and MGAT activity, which displays spe cific patterns during development.