MACM ILLANENCYCLOPED IA OF

CHEM ISTRY

Joseph J . Lagowsk i

Ed i tor i n Ch i e f

Vo l ume 4

MACM ILLAN REFERENCE USAS i mon & Schus t er Macm i l l an

NEW YORK

S i mon & Schus t er and Pren t i ce Ha l l In t erna t i ona lLONDON MEX ICO C ITY NEW DELH I S INGAPORE SYDNEY TORONTO

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S i mon & Schus t er Macm i l l an1633 BroadwayNew York , NY 10019

PR INTED IN THE UN ITED STATES OF AMER ICA

Pr i n t i ng Number

1 2 3 4 5 6 7 8 9 10

L IBRARY OF CONGRESS CATALOG ING - IN-PUBL ICAT ION DATAMacm i l l an encyc l oped i a o f chem i s t ry I ed i t ed by Joseph J . Lagowsk i .

p . cm .Inc l udes b i b l i ograph i ca l re f erences and i ndex .ISBN 0-02-897225-2 (se t : a l k . paper ) . - ISBN O-02-897221 -X

(v . 1 : a l k . paper ) . - ISBN 0-02-897222-8 (v . 2 : a l k . paper ) .- ISBN 0-02-897223-6 (v . 3 a l k . paper ) . - ISBN 0-02-897224-4(v . 4 : a l k . paper )

1 . Chem i s t ry -Encyc l oped i as . I . Lagowsk i , J . J .QD4 . M33 1997540 ' . 3-dc2 l 97-1824

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F i g . 9 . Reac t i ve pa th f rom v i ny l ogous am i de to v i ny lt r i f l a t e .

Cope per i cyc l i c reac t i on to g i ve the a l keny l cyc l ohep-t ad i ene 18 . In F i gure 8 the v i ny l brom i de 19 i s me t a l -a t ed (conver t ed by an organo l i th i um to a v i ny l an-i on) . The v i ny l an i on reac t s i mmed i a t e l y byi n t ramo l ecu l ar add i t i on to the ke tone to g i ve a prod-

uc t (21) re l a t ed to the h i gh l y f ragran t pa t chou l i a l co-ho l s . In F i gure 9 the v i ny l ogous am i de 22 undergoesN-a l ky l a t i on by the d i l odoa l kene 23 . Th i sd i i odoa l kene has bo th v i ny l i od i de and a l l y l i od i defunc t i ona l groups : the v i ny l i od i de i s comp l e t e l y un-reac t i ve to nuc l eoph i l es , wh i l e the a l l y l i od i de i sh i gh l y reac t i ve , reac t i ng a t the n i t rogen to g i ve 24 .The very poor reac t i v i t y o f v i ny l ha l i des toward nu-c l eoph i l es i s a consequence o f the grea t er e l ec t ronega -t i v i t y o f the sp1 hybr i d i za t i on , wh i ch des t ab i l i zes theaccumu l a t i on o f nega t i ve charge on the ha l i de tha tmus t occur i n the t rans i t i on s t a t e for nuc l eoph i l i cd i sp l acemen t . Fo l l ow i ng me t a l a t i on , v i ny l i od i de 23undergoes i n t ramo l ecu l ar con j uga t e add i t i on to g i veeno l a t e 25 ; wh i ch i s t rapped by the t r i f l a t e donor 26to g i ve the v i ny l t r i f l a t e 27 . Ca t a l y t i c hydrogena t i onreduces the a l kene and v i ny l t r i f l a t e func t i ona l groupsto comp l e t e a syn thes i s o f the i ndo l i z i d i ne 209D , oneo f severa l s t ruc tura l l y re l a t ed neuro tox i ns secre t ed bythe neo t rop i ca l po i son dar t f rogs . In F i gure 10 , theeno l a t e o f the me thoxy enone (a v i ny l ogous es t er ) 28i s t rapped by t r i me thy l s i l y l ch l or i de to g i ve the d i ene

S i (CH3)3

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OCH3 OCH3 OCH328 29 31

F i g . 10 . Reac t i ve pa th f rom the eno l a t e o f the me thoxyenone to v i ny l s i l y l e ther .

Aqueous Emu l s i on

rH C I i or Suspens i on Free rH C i iI \ / I Rad i ca l Po l ymer i za t i on I \ /I C=C I

__C-C__H HJ LH Hn 3 Po l yv i ny l ch l or i de

F i g . 11 . Po l ymer i za t i on o f v i ny l ch l or i de .

29 . Th i s d i ene undergoes D IELS-ALDER cyc l oadd i -t i on w i th the n i t roa l kene 30 to prov i de the v i ny l s i l y le ther 31 .

The i mpor t an t v i ny l po l ymers i nc l ude po l yv i ny l ac -e t a t e , po l yv i ny l a l coho l , po l yv i ny l e ther , po l yv i ny l i -dene ch l or i de , and the po l yv i ny l -ha l i des . The bes tknown v i ny l po l ymer i s po l yv i ny l ch l or i de (PVC) , athermop l as t i c po l ymer . V i ny l ch l or i de i s po l ymer i zed(F i gure 11) , t yp i ca l l y w i th a rad i ca l i n i t i a tor , to pro-v i de a powder tha t upon hea t i ng i n a mo l d fuses(cross- l i nks) , to a tough , durab l e p l as t i c . The add i t i ono f p l as t i c i zers , or copo l ymer i za t i on w i th ( for exam-p l e ) v i ny l ace t a t e or acry l on i t r i l e , g i ves equa l l y dura -b l e bu t ma l l eab l e PVC po l ymers . Po l yv i ny l ace t a t e i sused as a b i nder for pa i n t s and as adhes i ves ; po l yv i -ny l a l coho l i s a l so an i mpor t an t componen t o f adhe -s i ves and , as i t has proper t i es s i m i l ar to s t arch , i s usedas an emu l s i f i er and th i ckener .

B IBL IOGRAPHY

BEYER , H. ; WALTER , W. Handbook o f Organ i c Chem i s t ry ;New York : Pren t i ce -Ha l l Europe , 1996 ; pp . 73-89 , 95-98 , 329 .

1

JED F . F ISHER

V i s i on , Chem i s t ry o fV i s i on i s a spec i a l i zed form o f l i gh t de t ec t i on . The eyei s the organ o f v i s i on . I t cons i s ts o f op t i ca l e l emen t s ,such as the l ens , and a ne twork o f sensory ce l l s andneurons known as the re t i na . There are two t ypes o fpho torecep tor ce l l s i n the re t i na : rods and cones ,named because o f the i r charac t er i s t i c shapes . Rodce l l s are respons i b l e for d i m- l i gh t b l ack -and-wh i t ev i s i on , and cone ce l l s are respons i b l e for br i gh t - l i gh tco l or v i s i on . L i gh t s t r i k i ng a pho torecep tor ce l l i sconver t ed i n to an e l ec t r i ca l s i gna l by a pho tochem i ca lreac t i on . The s i gna l i s processed by o ther ce l l s i n there t i na and sen t to the bra i n . Key e l emen t s o f v i s i on i nhumans i nc l ude h i gh acu i t y , co l or sens i t i v i t y , andthe capab i l i t y for a l arge dynam i c range o f s i gna li n t ens i ty .

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V i s i on , Chem i s t ry o f

Pho torecep tor Mo l ecu l e

V ITAM IN A AND RHODOPS I N

A chromophore i s a chem i ca l group tha t producesco l or by absorb i ng l i gh t . The chromophore i n near l ya l l ver t ebra t e v i sua l p i gmen t s i s der i ved f rom v i t am i nA1 , a f a t -so l ub l e t erpene a l coho l o f the formu l aC20H300 . V i t am i n A1 i s an examp l e o f a compoundw i th a h i gh l y con j uga t ed sys t em o f a l t erna t i ng s i ng l eand doub l e bonds , a po l yene . I t has f i ve carbon-carbon doub l e bonds . The over l app i ng p-orb i t a l s o fad j acen t carbon a toms form a IT-bond . Each doub l ebond be tween ad j acen t carbon a toms cons i s ts o f oneo- - and one i r -bond .

V i t am i n A1 i s enzyma t i ca l l y ox i d i zed i n the re t i nato an a l dehyde , re t i na l . Re t i na l i s cova l en t l y a t t achedto a spec i f i c l ys i ne res i due i n the AM INO AC ID se -quence o f the ops i n pro t e i n to form the v i sua l p i g-men t rhodops i n . Rhodops i n i s the pho torecep tormo l ecu l e o f the rod ce l l . I t cons i s ts o f a pro t e i n (op-s i n) embedded i n to the spec i a l i zed d i sk membrane o fthe rod ce l l and a chromophore ( re t i na l ) . The pro-t e i n-chromophore l i nkage i n rhodops i n i s an unusu-

a l l y s t ab l e pro tona t ed Sch i f f base bond .The bond i ng o f the re t i na l chromophore po l yene

canno t be adequa t e l y descr i bed by a s i ng l e e l ec t rons t ruc ture . There fore , the bond i ng i s de l oca l i zed andd i sp l ays resonance , a we i gh t ed average o f canon i ca ls t ruc tura l forms .

The re t r i a l i n the i nac t i ve , or dark -adap t ed , s t a t eo f rhodops i n i s a spec i f i c geome t r i c i somer , 11-c i s - re t i na l . Geome t r i c i somers are poss i b l e becausethere i s h i ndered ro t a t i on abou t carbon -carbon dou-b l e bonds . The 11-c i s no t a t i on re f ers to the f ac t tha tthe carbon a tom cha i ns a t t ached to carbon a toms 11and 12 l i e on the same s i de o f the C11-C12 doub l ebond . Th i s resu l t s i n a bend i n the carbon backbonei n add i t i on to a s l i gh t tw i s t because o f s t er i c e f f ec t s o f

12

ops i n

l i gh t

H

® ops i n6~ l 2 H

F i g . 1 . The chem i ca l process o f v i s i on .

the me thy l group on carbon 13 . The s i ng l e carbon -carbon doub l e bond i n the i onone r i ng o f re t i na l (C5-C6) i s a l so i n the c i s or i en t a t i on i n rhodops i n . Thethree o ther carbon -carbon doub l e bonds i n the re t i -na l po l yene cha i n are i n the t rans or i en t a t i on .

RHODOPS IN PHOTOACT IVAT ION

V i sua l exc i t a t i on i s t r i ggered by pho to i somer i za t i ono f 1 1-c i s- re t i na l to the 11- t rans i somer w i th i n there t i na l b i nd i ng pocke t o f rhodops i n . The absorp t i ono f a pho ton , a quan tum o f energy , by rhodops i ncauses the pho to i somer i za t i on . A l though rhodops i ncan absorb a f a i r l y w i de range o f l i gh t energ i es , greenl i gh t i s mos t e f f ec t i ve i n ac t i va t i ng rhodops i n . The

wave l eng th o f l i gh t tha t i s max i ma l l y absorbed (Xmax

va l ue ) i s 500 nm .

Rhodops i n has an unusua l l y h i gh quan tum y i e l dfor a b i o l og i ca l sys t em . The quan tum y i e l d i s de f i nedas the f rac t i on o f absorbed l i gh t tha t resu l t s i n a par -t i cu l ar ou t come . The pr i mary quan tum y i e l d o f rho-dops i n i s abou t 0 . 67 , mean i ng tha t abou t two o fthree rhodops i n mo l ecu l es tha t absorb a pho ton un-dergo re t i na l pho to i somer i za t i on .

The re t i na l pho to i somer i za t i on i s the on l y l i gh t -dependen t even t i n v i s i on . Re t i na l i somer i za t i on veryrap i d l y conver ts l i gh t energy i n to mo l ecu l ar mo t i on ,or therma l energy . The new l y formed 11- t rans- re t i na li somer can then i n t erac t w i th spec i f i c am i no ac i ds o frhodops i n to cause a change i n recep tor con forma -t i on . The ac t i ve recep tor con forma t i on b i nds to aspec i f i c s i gna l - t ransduc i ng pro t e i n i n the cy top l asmo f the rod ce l l ca l l ed t ransduc i n . In th i s way , a pho-ton o f a spec i f i c wave l eng th i s absorbed by rhodops i nand conver t ed i n to a b i ochem i ca l s i gna l .

B i ochem i s t ry o f V i s i on

G PROTE IN CASCADE

The rod ce l l pro t e i n t ransduc i n t ransm i t s a b i ochem-i ca l s i gna l f rom rhodops i n to a ce l l u l ar e f f ec tormo l ecu l e . Transduc i n i s a guan i ne nuc l eo t i de -b i nd i ngregu l a tory pro t e i n , or G pro t e i n . Pho toac t i va t ed rho-dops i n ca t a l yzes the exchange o f guanos i ne 5 ' -d i phospha t e (GDP) for guanos i ne S ' - t r i phospha t e(GTP) by mu l t i p l e t ransduc i n mo l ecu l es . The ac t i -va t ed t ransduc i n , w i th GTP i n i t s nuc l eo t i de -b i nd i ngpocke t , then t ransm i t s a chem i ca l s i gna l to the e f f ec -tor mo l ecu l e i n the s i gna l i ng cascade . The e f f ec tormo l ecu l e i n the ver t ebra t e v i sua l sys t em i s the enzymeguanos i ne 3 ' : S ' -cyc l i c monophospha t e (cyc l i c GMP)phosphod i es t erase . A s i ng l e t ransduc i n mo l ecu l e ac t i -va t es a s i ng l e phosphod i es t erase mo l ecu l e .

Phosphod i es t erase ca t a l yzes the hydro l ys i s o f cy-c l i c GMP to guanos i ne 5 ' -monophospha t e (GMP)

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V i s i on , Chem i s t ry of

and i n t race l l u l ar l eve l s o f cyc l i c GMP drop . Thel ower l eve l s o f cyc l i c GMP cause a rod ce l l p l asmamembrane ca t i on channe l to c l ose . S i nce the p l asmamembrane i s se l ec t i ve l y permeab l e to i ons , wh i ch are

e l ec t r i ca l l y charged , an e l ec t r i ca l po t en t i a l d i f f erenceex i s ts be tween the i ns i de and the ou t s i de o f the rodce l l . The po t en t i a l i ncreases as ca t i on channe l s arec l osed and the i n f l ux o f sod i um and ca l c i um i ons ,wh i ch car ry pos i t i ve charge , i s s l owed . The resu l t i stha t the rod ce l l becomes hyperpo l ar i zed i n responseto l i gh t . The i ncrease i n po t en t i a l var i es propor t i on-a l l y w i th the s t reng th o f the l i gh t s i gna l . The changei n membrane po t en t i a l i s sen t as an e l ec t r i ca l s i gna lf rom the p l asma membrane to the synap t i c t erm i na lo f the rod ce l l , where i t i s t ransm i t t ed . to o ther spe -c i a l i zed ce l l s o f the re t i na .

S IGNAL AMPL I F ICAT ION

A proper l y dark -adap t ed rod ce l l can de t ec t a s i ng l epho ton . Th i s ext reme sens i t i v i t y i s poss i b l e i n par tbecause o f two i mpor t an t f ea tures o f the v i sua l sys-t em: (1) the s t ab i l i t y o f rhodops i n i n darkness to ther -ma l ac t i va t i on and (2) the h i gh degree o f s i gna l am-

p l i f i ca t i on by the b i ochem i ca l cascade o f v i s i on . I t hasbeen es t i ma t ed tha t the spon t aneous therma l i somer i -za t i on o f 11-c i s - re t i na l i n rhodops i n i n darknesst akes p l ace rough l y once i n 300-1 , 000 years . In con-t ras t , a s i ng l e pho ton can theore t i ca l l y cause as many

as 1 , 000 ca t i on channe l s i n a rod ce l l membrane toc l ose .

The l i gh t s i gna l i r turned o f f by a number o f b i o-chem i ca l mechan i sms . L i gh t -ac t i va t ed rhodops i n be -comes phosphory l a t ed by a spec i f i c rhodops i n k i nase

enzyme . The phosphory l a t ed form o f rhodops i n canno l onger i n t erac t w i th t ransduc i n . The ac t i ve GTP-bound form o f t ransduc i n has an i n t r i ns i c enzyma t i cGTP hydro l ys i s ac t i v i t y . Over t i me , the bound GTP i sconver t ed to GDP , and t ransduc i n re turns to i t s i nac -t i ve s t a t e . In add i t i on , i n t race l l u l ar ca l c i um l eve l s

drop a f t er the ca t i on channe l o f the rod ce l l c l oses . Af a l l i n i n t race l l u l ar ca l c i um concen t ra t i on med i a t es

pho torecep tor ce l l recovery and adap t a t i on .The process o f adap t a t i on a l l ows the sens i t i v i t y o f

the re t i na to ad j us t based on the l eve l o f l i gh t i n av i sua l scene . Adap t a t i on i s ext reme l y i mpor t an t for ause fu l v i sua l sys t em s i nce the magn i tude o f l i gh t var -i es w i de l y i n the env i ronmen t . For examp l e , br i gh tsun l i gh t and d i m s t ar l i gh t d i f f er i n l um i nance by a tl eas t severa l orders o f magn i tude .

Co l or V i s i on

Humans possess t r i chroma t i c co l or v i s i on , or t r i chro-

macy . Mos t peop l e can ma t ch any g i ven re f erence

co l or by comb i n i ng the three pr i mary co l ors . Thethree pr i mary co l ors for add i t i ve co l or m i x tures arered , green , and b l ue . In 1802 , Thomas Young hy-po thes i zed tha t t r i chromacy resu l t ed f rom humanshav i ng three separa t e co l or -sens i ng mechan i sms . I t i snow known tha t the re t i na con t a i ns three c l asses o fcone pho torecep tor ce l l s. Each c l ass o f cone ce l l i ssens i t i ve to a spec i f i c wave l eng th o f l i gh t .

At the mo l ecu l ar l eve l , human t r i chroma t i c co l orv i s i on requ i res the presence o f three cone p i gmen t sw i th broad over l app i ng spec t ra l absorp t i on . Each

spec i f i c cone c l ass con t a i ns on l y one t ype o f pho tore -cep tor mo l ecu l e . The three t ypes o f cone pho torecep-tor mo l ecu l es ( red , green , and b l ue ) are homo l ogueso f rhodops i n. The am i no ac i d sequences o f these op-s i ns are abou t 40 percen t i den t i ca l to tha t o f human

rhodops i n . The green and red ops i ns are abou t 96

percen t i den t i ca l to each o ther and abou t 43 percen ti den t i ca l to the b l ue ops i n .

The spec t ra l proper t i es o f human cone p i gmen t shave been s tud i ed by a var i e t y o f t echn i ques rang i ngf rom psychophys i ca l co l or ma t ch i ng to m i crospec -t ropho tome t ry . Us i ng t echn i ques o f mo l ecu l ar b i o l -

ogy , the human cone p i gmen t genes were expressedi n t i ssue cu l ture ce l l s , recons t i tu t ed w i th I 1-c i s - re t i -na l chromophore , and s tud i ed by u l t rav i o l e t -v i s i b l e

absorp t i on spec t roscopy . The ) tmax va l ues o f the p i g-men t s were es t i ma t ed to be 425 nm (b l ue cone ) ,530 nm (green cone ) , and 560 nm ( red cone ) . Theses tud i es con f i rmed the prev i ous ass i gnmen t s o f thec l oned p i gmen t genes , wh i ch were based on a gene t i cana l ys i s .

Rhodops i n and the three cone p i gmen t s a l l use thesame chromophore , 1 1-c i s - re t i na l . Th i s s i ng l e chro-

mophore a l l ows a l l v i s i b l e wave l eng ths " -o f l i gh t ,wh i ch range f rom abou t 400 nm (v i o l e t ) to 600 nm

(deep red) , to be de t ec t ed . A spec t ra l tun i ng med i a -n i sm ex i s ts so tha t a par t i cu l ar ops i n pro t e i n canmodu l a t e the absorp t i on spec t rum o f i ts re t i ny l i denechromophore . Spec t ra l tun i ng i s poss i b l e because

spec i f i c am i no ac i d s i de cha i ns o f each ops i n can i n-t erac t w i th the chromophore and sh i f t i t s Amax va l ue .

Among the f i f t een d i f f erences be tween the 364am i no ac i d human green and red p i gmen t s , sevenam i no ac i d changes are respons i b l e for the observed30-nm spec t ra l sh i f t i n go i ng f rom the green to thered p i gmen t . Mos t o f th i s sh i f t i s caused by am i noac i d s i de cha i ns tha t con t a i n a hydroxy l group : tyro-s i ne , ser i ne , and threon i r i e .

Gene t i c var i a t i ons i n co l or v i s i on may resu l t f rom amu t a t i on i n one o f the genes encod i ng a cone ops i n . I fthe am i no ac i d change a f f ec t s spec t ra l tun i ng i n oneo f the cone p i gmen t s , then one o f the cone t ypes w i l lcon t a i n a p i gmen t w i th an anoma l ous absorp t i on

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V i t am i ns

spec t rum . Ind i v i dua l s w i th th i s gene t i c var i a t i on areca l l ed anoma l ous t r i chroma t s . The mos t common

t ype o f anoma l ous t r i chromacy i s ca l l ed red -greenco l or b l i ndness . Red-green co l or v i s i on var i a t i ons a f -f ec t ma l es predom i nan t l y s i nce the genes for the redand green ops i n genes are found on l y on the X-chro-mosome .

Severe co l or v i s i on de f ec t s may resu l t f rom com-p l e t e de f i c i enc i es o f one or more o f the three coneops i n genes . Ind i v i dua l s who l ack a func t i ona l red or

green pho torecep tor are ca l l ed d i chroma t s .

Re l a t ed S i gna l i ng Sys t ems

NATHANS , J . " The Genes for Co l or V i s i on . " Sc i . Amer .1989 , 260 , 42-49 .

O ' BR IEN , D . F . " The Chem i s t ry o f V i s i on . " Sc i ence 1982 ,218 , 961-966 .

SAKMAR , T . P . " Ops i ns . " In Handbook o f Recep tors andChanne l s ; Boca Ra ton , FL : CRC Press , 1994 ; pp . 2S7-276 .

SCHNAPF , J . L . ; BAYLOR , D . A . " How Pho torecep tor Ce l l sRespond to L i gh t . " Sc i . Amer . 1987 , 256 , 40-47 .

STRYER , L . " The Mo l ecu l es o f V i sua l Exc i t a t i on . " Sd .Amer . 1987 , 257 , 42-SO .

STRYER , L . " S i gna l Transduc t i on Cascades . " In B i ochem i s-t ry , 4 th ed . ; New York : Freeman , 1995 ; pp . 332-339 .

WALD , G . " The Mo l ecu l ar Bas i s o f V i sua l Exc i t a t i on . "Na ture 1968 , 219 , 800-807 .

Rhodops i n i s a member o f a f am i l y o f re l a t ed seven-he l i ca l membrane recep tor pro t e i ns . O ther no t ab l emembers o f th i s f am i l y i nc l ude recep tors for the hor -mones adrena l i ne and g l ucagon . Transduc i n i s a l so amember o f a f am i l y o f re l a t ed s i gna l - t ransduc i ng Gpro t e i ns . The same genera l sys t em o f re l a t ed mem-brane recep tors and G pro t e i ns i s used by a l l eu-karyo t i c organ i sms - f rom humans to yeas t .

Membrane recep tor mo l ecu l es undergo a con for -ma t i ona l change i n response to the spec i f i c b i nd i ng o fa hormone l i gand i n the case o f hormone recep tors ,or the absorp t i on o f l i gh t i n the case o f rhodops i n . .Th i s con forma t i ona l change a l l ows the por t i on o f therecep tor on the cy top l asm i c sur f ace o f the p l asmamembrane to i n t erac t w i th spec i f i c pro t e i ns i n thecy top l asm o f the ce l l .

G pro t e i ns are one c l ass o f cy top l asm i c pro t e i nstha t i n t erac t w i th the ac t i va t ed membrane recep tor .The ac t i ve recep tor ca t a l yzes the exchange o f GDPfor GTP by mu l t i p l e G pro t e i n mo l ecu l es . The ac t i -va t ed G pro t e i n then t ransm i t s a chem i ca l s i gna l to ace l l u l ar e f f ec tor mo l ecu l e .

E f f ec tor mo l ecu l es may be enzymes or i on chan-ne l s . An e f f ec tor enzyme produces a sma l l b i oac t i vecompound known as a second messenger mo l ecu l e .For examp l e , adrena l i ne i s secre t ed i n to the b l ood-s t ream and b i nds to the seven-he l i ca l adrenerg i c re -cep tor . The hormone - recep tor comp l ex ac t i va t es aspec i f i c G pro t e i n , wh i ch i n turn ac t i va t es the e f f ec torenzyme adeny l y l cyc l ase to produce adenos i ne 3 ' : 5 ' -cyc l i c monophospha t e (cAMP) , wh i ch a f f ec t s ce l l u l arphys i o l ogy . In the v i sua l sys t em , the e f f ec tor enzymei s cyc l i c GMP phosphod i es t erase , and the secondmessenger mo l ecu l e i s cyc l i c GMP .

B IBL IOGRAPHY

HUNT , D . M . ; DULA! , K . S . ; BOWMAKER , J. K . ; MOLLON ,J . D . " The Chem i s t ry o f John Da l ton ' s Co l or B l i ndness . "Sc i ence 1995 , 267 , 984-988 .

THOMAS P . SAKMAR

V i t am i nsV i t am i ns are subs t ances tha t are essen t i a l for l i f e i nadd i t i on to the pro t e i ns , m i nera l s , f a t s , and carbohy-dra t es i n foods . To be cons i dered a v i t am i n , a sub-s t ance mus t mee t the fo l l ow i ng cr i t er i a :" I t i s an organ i c compound d i s t i nc t f rom f a t s , carbo-

hydra t es , and pro t e i ns ; i t musr be a na tura l compo-nen t o f foods , where i t i s usua l l y presen t i n m i nu t eamoun t s .

" I t i s essen t i a l , a l so usua l l y i n m i nu t e amoun t s , fornorma l phys i o l og i ca l func t i on ( i . e . , ma i n t enance ,grow th , deve l opmen t , and / or produc t i on

" I t s absence or underu t i l i za t i on mus t cause a spec i f i cde f i c i ency syndrome .

" I t i s no t syn thes i zed by the hos t i n amoun t s ade -qua t e to mee t norma l phys i o l og i ca l needs .

Th i s de f i n i t i on i s no t per f ec t i n tha t many spec i es cansyn thes i ze a t l eas t some o f these subs t ances . For ex-amp l e , mos t spec i es can syn thes i ze ascorb i c ac i d (v i -t am i n C) , cho l eca l c i f ero l (v i t am i n D) , and n i ac i n .On l y the f ew (e . g . , gu i nea p i gs , humans) who l ack theenzyme L-gu l ono l ac tone ox i dase requ i re a d i e t arysource o f v i t am i n C , and on l y i nd i v i dua l s no t ex-posed to sun l i gh t canno t per form the pho to l ys i s o f i t sprecursor me t abo l i t e , thus requ i r i ng v i t am i n D i nthe i r d i e t s . On l y those spec i es (e . g . , ca t s , ducks , andf i shes) who are very i ne f f i c i en t i n conver t i ng theAM INO AC ID t ryp tophan to n i ac i n requ i re the l a t t eras a v i t am i n . Thus the de f i n i t i on o f a v i t am i n shou l d

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