Liver and Small Intestinal Mucosa Lysoplasmalogenase and Nutrient Metabolism/Distribution

Abstract

Lysoplasmalogens, produced from plasmalogens by phospholipase A2, can disrupt cell membranes. Lysoplasmalogenase (Lpnase) catalyzes hydrolysis of the vinyl ether bond of lysoplasmalogen yielding an aldehyde and glycerophosphobase. We purified Lpnase from rat liver microsomes and identified the integral membrane protein as TMEM86B, a member of the YhhN family- conserved from bacteria to humans. In mammals the activity of Lpnase is very high in liver and small intestinal (S.I.) mucosa, low in brain, and undetectable in heart and smooth muscle. We tested the hypothesis that liver and S.I. Lpnase is involved in nutrient metabolism/distribution by examining microsomal enzyme activities in: 1. Adult livers during pregnancy, lactation, and post lactation. 2. Pups' livers and S.I. mucosa during early development. During gestation the units and specific activities (SA) of liver Lpnase were similar to non-pregnant (N-P) controls. During 20 days (d) of lactation (10 pups) the units of Lpnase increased by 90%; the liver wet weight (ww), and the tissue- and microsomal- protein values each increased by 88%. During 20 d following weaning, these values returned to N-P levels. Throughout these 40 d, the SA of Lpnase remained constant: 64 nmol/min/mg pro. In development, the SAs of liver Lpnase were 28% and 75% of adult levels at post natal days (PN) 4 and 20, respectively. Slower development of the S.I. Lpnase occurred: 8% and 36% of adult SA levels were reached at PN 4 and 20, respectively. The data suggest that liver and S.I. Lpnase may function in the metabolism and/or distribution of nutrients. A model: Plasmalogens enriched in PUFAs are synthesized in liver, carried to brain via HDLs where PUFAs are delivered. Lysoplasmalogens in the HDL remnants return to liver and S.I. where they are catabolized by Lpnase.