collaboration with Dr. Howard Brockman (Hormel 
Institute). 
In a second set of studies, a newly discovered 
pathway of animal cell phospholipid biosynthesis is 
being characterized. Recent experiments in Dr. 
Glomset's laboratory showed that animal cells in 
culture readily convert 5«-2-arachidonoyl monoa- 
cylglycerol into 5n-l-stearoyl-2-arachidonoyl spe- 
cies of several membrane phospholipids, including 
phosphatidylinositol, phosphatidylethanolamine, 
and phosphatidylserine. In addition, experiments 
with cell-free systems provided evidence that a 
monoacylglycerol kinase activity initiates the mono- 
acylglycerol incorporation pathway by converting 
monoacylglycerol into 5n-2-acyI lysophosphatidic 
acid and that a stearoyl-specific, coenzyme A- 
dependent transacylase activity catalyzes the next 
step in the pathway by converting xw-2-acyl lyso- 
phosphatidic acid into 5n-l-stearoyl-2-acyl phos- 
phatidic acid. Subsequent experiments with a 
similar transacylase activity from bovine testis mem- 
branes provided more-detailed information about 
the enzyme's substrate specificity and mechanism of 
action. Attempts to purify the enzyme and deter- 
mine its intracellular location are under way, as are 
attempts to obtain more-detailed information about 
other enzymes in the pathway. 
A third set of studies (in collaboration with Dr. 
Andreas Habenicht, University of Heidelberg) is de- 
signed to provide information about metabolic 
pathways that deliver arachidonic acid for eicosa- 
noid formation in animal cells. An initial study of 
human skin fibroblasts in culture demonstrated that 
the classical, low-density lipoprotein (LDL) recep- 
tor-dependent pathway of LDL uptake delivers ara- 
chidonic acid for eicosanoid production during 
the cell cycle; a recent study showed that the 
LDL receptor-dependent pathway also provides 
arachidonic acid for eicosanoid production in 
freshly isolated, human blood-derived monocytes. 
Importantly, the monocytes convert the arachidonic 
acid into products of the prostaglandin H synthase 
pathway, even in the absence of agonists that in- 
crease the concentration of intracellular calcium 
ions. In contrast, they convert the arachidonic acid 
into products of the 5 -lipoxygenase pathway only in 
the presence of such agonists. Experiments are 
currently under way to determine whether an LDL 
receptor-dependent pathway of arachidonic acid de- 
livery also operates in other cells, such as those of 
the adrenal cortex. 
A fourth set of studies concerns membrane 
proteins that are post-translationally modified by 
one or more thioether-linked, 20-carbon isoprenoid 
groups (geranylgeranyl groups) . Previous studies by 
Dr. Glomset's group in collaboration with others 
showed that several of these proteins, including 
the proteins rab 3A and G25K (CDC42Hs), are 
members of the ras superfamily of low-molecular- 
weight GTP-binding proteins. Studies of the mecha- 
nism of binding of these proteins to specific cell 
membranes are currently in progress. 
Dr. Glotnset is also Professor of Medicine and of 
Biochemistry at the University of Washington 
School of Medicine, Seattle, and Core Staff 
Member of the Regional Primate Research Center 
at the University of Washington. 
Books and Chapters of Books 
Gelb, M.H., Farnsworth, C.C., and Glomset, J.A. 
1992. Structural analysis of prenylated proteins. 
In Lipid Modification of Proteins: A Practical 
Approach (Hooper, N.M., and Turner, A.J., Eds.). 
Oxford, UK: IRL Press, pp 231-257. 
Salbach, P.B., Janssen-Timmen, U., Glomset, J.A., 
Schettler, G., and Habenicht, A.J.R. 1992. LDL- 
dependent eicosanoid formation in monocytes. In 
Atherosclerosis IX: Proceedings of the Ninth In- 
ternational Symposium on Atherosclerosis 
(Stein, O., Eisenberg, S., and Stein, Y., Eds.). Tel 
Aviv, Israel: R & L Creative Communications, pp 
363-366. 
Articles 
Applegate, K.R., and Glomset, J.A. 1991. Effect of 
acyl chain unsaturation on the conformation of 
model diacylglycerols: a computer modeling 
study, f Lipid Res 32:1635-1644. 
Applegate, K.R., and Glomset, J.A. 1991. Effect of 
acyl chain unsaturation on the packing of model 
diacylglycerols in simulated monolayers. / Z?/?/f/ 
Res 32:1645-1655. 
Glomset, J.A., Gelb, M.H., and Farnsworth, C.C. 
1992. Geranylgeranylated proteins. Biochem Soc 
Trans 20:479-484. 
Itabe, H., King, W.C., Reynolds, C.N., and Glom- 
set, J.A. 1992. Substrate specificity of a CoA- 
dependent stearoyl transacylase from bovine tes- 
tis membranes. /5?o/ Chem 261 •.15^19-15525 . 
Lemaitre, R.N., and Glomset, J.A. 1992. Arachi- 
donoyl-specific diacylglycerol kinase. Methods 
Enzymol 209:173-182. 
Salbach, P.B., Specht, E., von Hodenberg, E., Koss- 
mann, J., Janssen-Timmen, U., Schneider, W.J., 
Hugger, P., King, W.C., Glomset, J.A., and 
Habenicht, A.J.R. 1992. Differential low density 
lipoprotein receptor-dependent formation of ei- 
cosanoids in human blood-derived monocytes. 
Proc Natl Acad Sci USA 89:2439-2443. 
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