This collaboration is aimed at solving the long-standing dilemma of the pathway of prostaglandin biosynthesis in coral. Certain corals contain huge levels of prostaglandins (2-3% of their dry weight) and all the evidence from the early 1970's to the present suggests that they are not formed by the well-characterized cyclooxygenase enzyme as in mammals. The main possibilities include a lipoxygenase pathway via an unstable allene oxide, or a novel lipoxygenase pathway that leads to an endoperoxide intermediate. Previous work with prostaglandin-containing corals by Dr Brash and others has failed to unravel the metabolic pathway largely because the formation of optically active prostaglandins was not detected under in vitro conditions. Dr Samel of the Estonian National Academy of Sciences has now found a coral from the White Sea (north Russia) that does form prostaglandins with all the correct stereochemistry of the natural products. This FlRCA collaboration is aimed at following up on these observations, to delineate the mechanism of the coral prostaglandin biosynthesis and the properties of the enzymes involved. Often the fundamental biochemistry of eicosanoid biosynthesis has been elucidated first in plant and lower organisms. In this case the key to a novel pathway of prostaglandin synthesis is awaiting discovery in coral. The biosynthesis of novel eicosanoids is subject of the parent RO1. This collaborative project aims to extend this theme with resolution of the 20- year enigma of the prostaglandin pathway in coral.

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
Small Research Grants (R03)
Project #
1R03TW000404-01
Application #
2291995
Study Section
Special Emphasis Panel (SRC)
Project Start
1994-09-30
Project End
1997-09-29
Budget Start
1994-09-30
Budget End
1995-09-29
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Pharmacology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212