Richard Kulmacz, Ph.D., Professor
Rice University, 1978
The University of Texas
Health Science Center at Houston - Medical School
Department of Internal Medicine
Division of Hematology
6431 Fannin, MSB 5.288
Houston, Texas 77030
Tel: 713-500-6772
Fax: 713-500-6810
richard.j.kulmacz@uth.tmc.edu

Research Interests
Eicosanoids are very potent cellular signalling molecules derived from polyunsaturated fatty acids. Their name comes from the prototypical polyunsaturated fatty acid, eicosatetraenoic acid (arachidonic acid), and the class includes prostaglandins, leukotrienes, hydroxy fatty acids, and epoxy fatty acids. Eicosanoids have been implicated in a wide variety of pathophysiological processes, including carcinogenesis, hemostasis, inflammation, renal function, reproduction, and sleep/wake cycles. My general interest is in understanding at the molecular level how eicosanoid biosynthesis is accomplished and how it is regulated.
A major control point in eicosanoid biosynthesis is the initial oxygenation of fatty acid to form a lipid hydroperoxide, catalyzed by one of several fatty acid oxygenases. My lab's focus at present is on prostaglandin H synthase, the oxygenase which catalyzes the initial step in the synthesis of all prostaglandins. There are two isoforms of the synthase, which have distinct physiological functions and distinct regulation at the level of catalysis. We are interested in relating the catalytic differences between the isoforms to specific structural differences between the two proteins.

Selected Publications
Bambai, B., and Kulmacz, R.J. (2000) J. Biol. Chem. 275, 27608-27614. Prostaglandin H synthase: effects of peroxidase cosubstrates on cyclooxygenase velocity.

Guo, Q., and Kulmacz, R.J. (2000) Arch. Biochem. Biophys. 384, 269-279. Distinct influences of carboxyl terminal segment structure on function in the two isoforms of prostaglandin H synthase.

Tsai, A.-L., and Kulmacz, R.J. (2000) Prostaglandins Other Lipid Mediat. 62, 231-254. Tyrosyl radicals in prostaglandin H synthase-1 and -2.

Wu, G., Vuletich, J.L., Kulmacz, R.J., Osawa, Y., and Tsai, A.-L. (2001) J. Biol. Chem. 276, 19879-19888. Peroxidase self-inactivation in prostaglandin H synthase-1 pretreated with cyclooxygenase inhibitors or substituted with mangano protoporphyrin IX.

Wang, L.-H., and Kulmacz, R.J. (2002) Prostaglandins Other Lipid Mediat. 68/69, 409-422. Thromboxane synthase: structure and function of protein and gene.

Peng, S., Okeley, N.M., Tsai, A.-L., Wu, G., Kulmacz, R.J., and van der Donk, W.A. (2002) J. Am. Chem. Soc. 124, 10785-10796. Synthesis of isotopically labeled arachidonic acids to probe the reaction mechanism of prostaglandin H synthase.

Tsai, A.-L., Palmer, G., Wu, G., Peng, S., Okeley, N.M., van der Donk, W.A., and Kulmacz, R.J. (2002), J. Biol. Chem. 277, 38311-38321. Structural characterization of arachidonyl radicals formed by aspirin-treated prostaglandin H synthase-2.

van der Donk, W.A., Tsai, A.-L., and Kulmacz, R.J. (2002) Biochemistry 41, 15451-15458. The cyclooxygenase reaction mechanism.