r C, U 
2.3 1 3 PROGRAM
0%   9 8 11:50-12:00 Discussion
{9 (I) a u
g i 2 Ninth Annual Symposium on ' . 1.30 P.M. SyntheticModels of Reactive
 o E, 9:00 A.M. CoffeeChemistry-Physws Room Intermediates in the Catalytlc
E ; a 137 Cycle of Cytochrome P-450
'5 g Q Chemlstry and 9:30 Welcome and Introduction Professor Groves
a E g . Chemistry-Physics Room 139 High valence iron-porphyrin spccies are suspected to be re-
8 (73 E MOIBCUIar BlOlogy 9:40 Cytochrome P-450 Structures and Spons'ble for hydrocarbon mm? m me calalyllc ewe 0
('3 < ff. R t. cytochrome P450. The preparation, characterization and re
g 2 eac ions action of synthetic models of these reactive intermediates will
Ur established in memory of PTOfESSOY Gunsalus be described. Comparisons will be made between the reac
A S N ff The P450 heme sulfur proteins of monoxygenase systems tions of these synthetic compounds and those of liver micro
nna ' a encompass a range of synthetic and carbon cycling selectiv- somal cytochrome P'450
ity, oxygen donor cycles, and product yields. They share , ,
unique transient and stable intermediate states, dioxygen 2:20 DISCUSSlon
cycle, resonance spectra of the iron reporter group and pri 2:30 Coffee Break
mary sequence of the thiolate axial ligand. _ -
The microsomal heme sulfur~two flavin reductase systems 2'50 Strucmre and Function 0f
_ contrast in broad substrate and induction potential, weak Isozymes 0f CytOChrome P450
 substrate binding, low turnover and lipid dependence with PFOfeSSOF C000
STRUCTURE .16 three component systems (P450rcdoxinsingle FAD fla Cytochrome P450, the most versatile biological catalyst
Kig'reductase) 9f [2c rigitochondrdia and milcrobes WhiCh ex known, occurs widely in nature, being membrane-bound in
iitmre striete 'ae r . v v) - - -. , -- - -
AND FUNCTION corporaiionreincreasedusubbstrlatzliindlicnf; :Ziiioreicfityziffrfniiiy animal tissues and apparently cytosohc m microorganisms.
  Some of the most puzzling properties of P-450 in liver
underlredox modulated 1?er higher turnover and cou microsomes, including the remarkably broad substrate spec
OF pling 1" oxygenated product yields. Structure-function com- ificity and the ability to carry out both oxygen activation and
parscins of th Lhre: cggigoonent prOCSri/ote hygroxylase peroxide activation, could not be explained until the enzyme
CYTOCHROME P-450 mo es PFOVI e  [Y I e , cam (50161 yene) an P450113 system was resolved into its components (phospholipid, re
(8 methyl and 8 hydroxyl methyl) 1th monoxygenase vari ductase, and isozymes of P-450) and these were obtained in
eties from eucaryote organelles are now becoming available. purified form. Seven distinct isozymes have now been ob-
 The roles Of primary and tertiary structures present a target tained in an electrophoretically homogenous state from rab
Of general biochemical opportunity for the investigation 0f bit liver microsomes and characterized. They have a number
substrate and protein component determinants 0 comple of similar properties but differ significantly in spectra, pep
ment, 1 prec1510n and deg) the phy51cal probe analyses 0f tide maps, N and Cterminal amino acid sequences, patterns
Speakers Stat: structures and dynamic events. of induction, and activity toward selected substrates, whether
, , naturally occurring lipids or foreign compounds including
PROF. LC. GUNSALUS 10:30-10:40 DISCUSSlon drugs, and carcinogens. We have recently identified a highly
PROF D DOLPHIN 10:40 Coffee Break conserved cysteine-containing tetradecapeptide WHO: l:nay
, . . . . provide the sulfur ligand to the heme iron atom an ave
11'00 The Strugture _and ReactiVity 0f shown that the rabbit phenobarbitalinducible isozyme has
PROF. J. GROVES Intermediates m the CytOChrome 8070 homology in primary structure with the corresponding
PROF M COON P-450 Reaction Cycle rat protein. The purified isozymes exhibit individual prefer-
' ' Professor Dolphin ences for particular substrates but are all apparently capable
r g Model and enzymatic studies have suggested structures for Of blildmg. a variety of hydrophobic substrates. AS al-resultg
g :i - the coordination sphere around the heme iron for each of the disposition 0f foreign compounds and the metabo 15m. 0
Q? :2 c 3 Aprll 22, 1983 . . . . phySiologically occurring substances such as fatty aCIds,
 a; i 21 D f ' the enzymatically important intermediates 0f Cytochrome .P- prostaglandins and steroids are closely interrelated.
:2; a? .06 "0 epartment 0 Chemistry 450. Ustng ruthenium porphyrins, an analog for the Fe (iv)  
p :5; 9 g 113 UanCISity Of Kentucky oxy 1rcation radical has been characterized. The role of this 3:40 Discussion
3 g 0;: E. LCXlI'l t 1'1 K t k 40506 intermediate in P-450 function and its relationships to en- ' .
5 E: g 0  en 11C y zymic intermediates in catalases, peroxidases, and cyto 3:50-4:30 Meeting With Graduate SlUdentS
= chrome oxidase will be considered. and FacultyC-P Room 137