# LIPID METABOLISM IN NORMAL DISORDERS OF KERATINIZATION

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1988 · $140,797

## Abstract

This proposal represents a continuation of the applicant's interest in
lipid metabolism in disorders of cornification.  There are two major
thrusts to this work.  First, the applicant will explore the mechanisms of
sterol regulation in the skin.  Since it has been shown that lipoprotein
cholesterol does not regulate epidermal cholesterol synthesis, the
candidate will determine whether stratum corneum polar sterols such as
cholesterol sulfate or oxygenated sterols are regulators.  In addition to
sterologenesis, the applicant will also study another product of
3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase, the rate-limiting
enzyme of the cholesterol biosynthetic pathway, that is potentially
important for energy production (ubiquinones) in the epidermis.  To resolve
these points the applicant first will utilize normal cultured human
fibroblasts, attempting to validate cell culture results in organ culture
and the whole animal.  Elucidation of epidermal sterol metabolism is likely
to provide important insights not only into sterologenesis, but also into
more general effects of HMGCoA products on cell function.

The second major thrust is aimed at a further elucidation of the lipid
abnormalities in inherited recessive disorders of cornification.  Since
intercellular lipids appear to be one factor that controls desquamation,
discovery of the basic defect in these diseases will provide new insights
both into the role of certain lipids in normal epidermal function, and more
rational approaches to therapy of these sometimes devastating diseases.  In
addition to the well-appreciated importance of sterols for cornification,
best exemplified by fork of the applicant and others on recessive x-linked
ichthyosis, the applicant is studying two autosomal recessive diseases:  a)
non-bullous congenital ichthyosiform erythroderma (CIE), where she has
shown that aliphatic hydrocarbon accumulation is associated with
ichthyosis; and b) Chanarin-Dorfman Syndrome (CDS, neutral lipid storage
disease), a multisystem disorder, including ichthyosis, that is associated
with abnormal fatty acid metabolism.  In both diseases the basic defect
will be sought in cultured cell lines established from these patients.  CIE
is of general interest because it suggests for the first time that alkanes
may have a previously unrecognized role in mammalian cell function, while
CDS is important because it promises to open up a relatively unexplored
field of lipid metabolism, namely that of intracellular triglycerides.

## Key facts

- **NIH application ID:** 3155723
- **Project number:** 5R01AR029908-06
- **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:** 1988
- **Award amount:** $140,797
- **Award type:** 5
- **Project period:** 1981-07-01 → 1988-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155723

## Citation

> US National Institutes of Health, RePORTER application 3155723, LIPID METABOLISM IN NORMAL DISORDERS OF KERATINIZATION (5R01AR029908-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3155723. Licensed CC0.

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