# NORMAL SKIN LIPID METABOLISM & CORNIFICATION DISORDERS

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1990 · $158,887

## Abstract

In mammalian skin, permeability barrier function and desquamation are
mediated by intercellular stratum corneum lipids.  The metabolic pathways
whereby epidermis generates lipid for these stratum corneum functions is
not well-understood, however, several inherited skin diseases characterized
by abnormal desquamation and associated with discrete lipid metabolic
defects provide models for the study of these pathways.  Some diseases are
characterized by accumulation of very long chain (v.l.c.) n-alkanes, also
found in normal skin.  These studies are based upon the hypothesis that
epidermis synthesizes alkanes from fatty acids or alcohols; that changes in
the number or function of peroxisomes, a cellular organelle involved in
fatty alcohol and v.l.c. fatty acid metabolism, are involved in n-alkane
accumulation in outer epidermis; and that delineation of the underlying
defect in neutral lipid storage disease (NLSDI), where triglycerides
accumulate in viable cells, but alkanes accumulate in stratum corneum, will
further illuminate the origin of epidermal alkanes.  The defect in NLSDI is
postulated to be an intercellular triacylglycerol lipase that generates
diacylglycerols for phospholipid biosynthesis.  Evidence for alkane
biosynthesis will be sought using radiolabelled v.l.c. fatty acids in
cultured human keratinocytes (CHK), rodent epidermis in vivo, and in mutant
fibroblasts and products analyzed by radiochemical GLC.  The relationship
of alkane synthesis to differentiation will be assessed in isolated
epidermal layers and in CHK cultured by a variety of methods designed to
alter differentiation.  Peroxisomes will be quantitated in relation to
differentiation by ultrastructural cytochemistry for catalase and by three
functional assays for peroxisome specific pathways in both CHK and rodent
epidermis.  The cause of NLSDI will be probed in three NLSDI fibroblast
cell lines using radiolabelled precursors and by measurement of pool size
using recombinant diacylglycerol kinase.  Delineation of the metabolic
defect in NLSDI will contribute to our understanding of glycerolipid
metabolism and to the origin of epidermal alkanes.  Studies with mutant
cells which exhibit defects in v.l.c. fatty acid oxidation will aid in our
understanding of the role of peroxisomes in normal epidermal lipid
metabolism.

## Key facts

- **NIH application ID:** 3155724
- **Project number:** 5R01AR029908-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **SAM.gov UEI:** KMH5K9V7S518
- **Principal Investigator:** MARY L WILLIAMS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $158,887
- **Award type:** 5
- **Project period:** 1981-07-01 → 1992-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155724

## Citation

> US National Institutes of Health, RePORTER application 3155724, NORMAL SKIN LIPID METABOLISM & CORNIFICATION DISORDERS (5R01AR029908-08). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3155724. Licensed CC0.

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