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Journal of Lipid Research, Vol. 23, 619-626, May 1982
Copyright © 1982 by Lipid Research, Inc.

Sterol synthesis by the ocular lens of the rat during postnatal development

Richard J. Cenedella

Department of Biochemistry, Kirksville College of Osteopathic Medicine, Kirksville, MO 63501

Great amounts of plasma membranes are formed during early postnatal development of the ocular lens as lens epithelial cells differentiate into fiber cells. Little information is available on the source of the lipids, and particularly cholesterol, required for formation of these plasma membranes. The present study measured the capacity of the lens of the rat to synthesize cholesterol during this dynamic period of growth. Incorporation by lens of ³H₂O into total fatty acids was also examined. Absolute rates of cholesterol synthesis per whole lens were estimated in vitro from incorporation of ³H from ³H₂O into digitonide precipitable sterols (DPS) by intact lenses of 6- to 30-day old rats. Rates of cholesterol synthesis were calculated which were adequate to furnish from either 50-100% or 20-40% of the cholesterol required by the lens for growth, depending upon the animal's age and upon whether one considered NADPH to be generated by the pentose phosphate pathway or by oxidative enzymatic processes (NADPH from the pentose pathway is not labeled from ³H₂O). Generation of the NADPH necessary for cholesterol synthesis principally by the pentose pathway would support the higher percent contribution of synthesis to the total growth requirement. The pentose pathway was clearly active in the young rat lens, since between 7.5 to 9.0 times more [1-¹⁴C]glucose than [6-¹⁴C]glucose was oxidized in vitro to ¹⁴CO₂ by 6- and 22-day old lenses. Incorporation of ³H₂O into DPS decreases sharply after 2 weeks of age in spite of a constant rate of cholesterol accumulation by the lens. These results indicate that the ocular lens of the rat can furnish most if not all of its cholesterol requirements by synthesis de novo during the first 2 weeks of life, and imply a contribution from another source at older ages. Whether lipoproteins can supply cholesterol to the lens is still unclear, although neither HDL nor LDL altered the incorporation in vitro of [U-¹⁴C]glucose into DPS by lens.—Cenedella, R. J. Sterol synthesis by the ocular lens of the rat during postnatal development.

Supplementary key words digitonide precipitable sterols • cholesterol synthesis • fatty acid synthesis • pentose phosphate pathway • HDL • LDL

Submitted on June 23, 1981
Revised on November 12, 1981

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