"*4“. (~-

 

THE REPLACEMENT 0F CYSTINE
BY SOME PHENOLS IN METABOLISM .
'Thesls for Degree of M. S.

I Shwen-yuing Chen . A
l926__ '

 

        

_/_\
ugunvc7a'6 Y1;
‘ MN I " 5% r

1'33 HEW" (1' «arm I! 80!! mm
II mum!“

than
me“ to tho Faulty ¢
th- lhhku Sat. 00110:.
In Mu! fulfill-Int
at th. mum-Int.
d‘ tho
later of Educ- Dam

3!

Shun-yum; Ohm
July, 1926

2!- int» vinhu to think
Put. 3. D. 1.wa sud Pt. 3. 6. M.
for their “shunn- and within
h tho mounts: or this we“...

331618

in “PM”! W 018?!!! I! I” Pill”
a mum:

Introdnotin

tho oombnotion of tho oooioilohlo food notoriol oo gluoooo tur-
niohoo tho ouorgy ooooooory for tho nointoouoo of tho living orgonio-o.
Int tho protoino, oorholvltotoo. toto on! thoir iorivotiwoo in tho food
no only oxidioohlo through tho ootiwotia; of argon (or hydrogoo.) Gonor-
olly tho prooooooo or pivoiologiool ouidotiono oro hold to ho oooonliohod
through two ogonoioo. tho 1o onsywio, which bringo ohout diroot ciao-
tiono. ‘l’ho othor i. brought ohout by l-ooooptoro, oo gamma whioh
otfooto oxidotiu through o. roootion of «mogonotion. rho on group in
tho oyotoino W at glutothion (zcnzsnannzaom o zoomugcnzcnnzoom -

320) hoo tho proporty or toting up out giving off hydrogoo oo roprooontol
by tho following oquotiom

MA

81-“ o n V— m

oxidiood roduood
rho nouooo fan of glutothion in hoing can“ no: produoo tho oyotioo
«uplox and Magoo poroaido oo:

an o 03 ----9 18-8! 9 [303
rm poroxilo will tlmo nob turtho‘r ouidotion poooiblo, ow tho uidiood
rm roooting with wotor no: liboroto oxygon u:

”-8! o- 320 ———) 2m 0» 0

ibdorhollon and Northoilor (Ax-oh. goo. Pivoiol. (Pflugoro) 1”,
£15.20 1928) ohowod thot tho onto- oyotino : oyotoino io o noohonion

-1-

whidn onohloo tho oollo to bring obout tho tronoi’onotioo of oliolwoo into
ooid ooo olooholo. 'l'ho odditiu of oyotioo roworo tb prolution of oliolqoo
whilo tho oodition of oyotoino foworo tho torutiu of oloohol. In «pori-
oontiog with pigoono thoy oloo {out thot tho hirdo rod on o diot of poliohod
rioo oxolooiwoly ohowod o foiluro to utilioo tho oxygoo of tho hlooi non-oily.
Thio woo oooonpooiod by o loworod body tooporoturo one! o doproooioo at tho
goooouo notoholion. Sinoo tho tioouo oxtrooto of tho rioo-tod pigoono ooold
not offoot tho roduotion at oyotino, it woo intorprotod thot up dirootioo
of tho woll holonood roootioo ”-83 z." ”I o 8!! only gooo i‘ru right
to loft rooulting in tho look at lorooptor groupo oooouory for tho uiiotioo.
In oyohido poiooniog m roootiu gooo ru- ns-ao —-.» m , an in:
otiliootioo of tho norooptor groupo for ouiiotioo io iopoooihlo. I

Goldoohlidt (Aroh. Ophthollol., 1917, x0111, “7) oholoi thot
thoro :- ammua at oyotim in odult m. on! em ootoroot :- duo to
tho look of oyrtoino or mobility of oyotino to torn oyotoino.

With rogord to tho offoot or phonolo in ootohol'iol, luotoa on!
Lighthody (Unpoh. work) hovo town! ovidonoo thot tho ditqiroq-phonolo on
oorvo. «- phyoiologiool function oo. shown by tho mama or thooo phonolo
to oolo roohot producing dioto.

Tyrooioo. ono of tho ilportont onino «1a- in nutrition. in do-
onpooition by oolon bootorio yieldo phonol, which con to oxidiood to for:

pyroootoohol or hydroquinono oo:

2 6 oxidotion 6 m 0-

ft» phonolo oro thou oxorotod in tho urino in Minotiou with oulphurio
ooid or to oortoio utont with gluourmio ooid.

Upon furthor ooidotioo in tho oouroo of utobolioo tho bonoo’no
ring io broho. i'ho roooorohoo of Joffo ohowod thot on odoiniotrotioo of
boooono to dogo oooll oncooto of monio ooid on bo ioolotod from tho
urino. Io roprooouto thio roootioo oo followo: *

q/ck oxidotioo cop o‘ocn
._._._——-_9 m
03%03/ \\ an ' aux/an luoooio ooid

lijlono ond Vorotoigh (Arch. g“. Phyoiol. (Pflugoro) 1”, 416-28.
1922) hovo ohown thot hydroqoinouo odoiniotorod to oioo on! guiooo pigo in
ovor dooo couooo oorhod motor diotnrboncoo of tho hoort. oro-po. opiothotoooo
ond othor offooto.

rho poooiblo noohonioo of the cation of thooo dihydrooyphooolo in
notoboliol no: bo ooggootod oo following:

1) According to Ioilondo dohydrogonotion idoo (lor. 1912, 45,
4M.) hydroquinono io oxidiood to quinono by oxygon froo pollodim. rho
oaidotion oonoioto of tho rooml of lobilo hydrogoo which io to!!! up by
pollodiuo. Gluoooo io oooily oxidiood to oorbon dioxido ond wotor ot low
to-poroturo by quinouo oo on oocoptor for Magoo in tho oboonoo of olooon-
tory canon. looot (liootor thooio, Hiohigon Btoto Gollogo. loco) oho‘od
thot quioono in‘wotor for-o hydroquinono oo o rovoroihlo roootion. Tho
quinono ottocho tho wotor nolocolo with liborotia of ootivotod oxygoo oo:

m

9
2) Rn'oyuio oxidation thom‘y.
t

It hoo boon known that in oninolo ond plonto thoro oro oxidoooo
or oxidising onoynoo effecting oxidation, which ordinorily con not ho

 

brooght oboot by oolooulor ongoo olooo ouoh oo tho blooing of gooioou.
tho oouworoion of ludroquioono to qoioooo, oto.

Ohodot ond Booh (am dor Iiooholioohoh orboito nothodoo
I. ibdorholdon, Borlio. 1910. Vol. 8 pp. ‘24?) omidor on oaidooo oo
ooopoood of on oxygooooo ond poroxidooo. rho oxygonooo boing onyx-o lib
unitoo with tho uygon of tho oir to for: poroxidoo. Tho poroxidooo ooto
upon tho poroxido ond roodoro ono otoo of ito oxygoo ootiwo for oubooqoont
nidotioo of on ocooptor. ‘rho roootioo io opproxi-otoly oo followo:

no 0-0: ————> 2A0: (Poruido)

A0

2
According to molow (bioobo J. M. 536) tho ouidooo io o throo

o Poruidoooa A0 9 O

ooopoaont oyotoo. mo oombor io on organio oubotonoo ond probobly io on
oroootio ooopound with two hydrowy groupo in tho o-pooitioo or o ootoohol
oubotonoo. Upon ooidotim tho ootoohol will boooloo orthoquinuo. 'I’ho othor
two oro oooyno. mono" which ootolyooo tho produotioh of poroxidoo (or
tho owidotion of tho ootoohol) ond o porosidooo which doooqoooo tho por-
oxidoo with tho for-lotion of ootivo canon. fhuo tho orthoquinoao poroxido
io ootod upon by o poroxidooo to yiold ootiwo oxygon with tho foo-notion of
ootochol.

In oxporioonting with tho tioouo ond tioom outrooto d plonto
oho found thot thooo oontoioing oooo oohotonoo with ootoohol grouping givo
o bluo color with guoioouo tinoturo. Iho oloo found thot ootochol. odron-
olin, ond oonpomdo th c-dihydraoy groupingo toad to ooidioo olowly whoo
loft in tho oir with tho formation of poromidoo, tho oaygoo of which con
bo ootiwotod by porowidoooo.

fl! oxidotioo of guoioonl, porophonylon-dionino, ond phonolphtholin
by hydrogon poroxido ado:- tho influonoo of tho porosidooo of milk io groot-

ly occolorotod by phoool ond oroool (notlo ond Porch Bygonio Lobmtory
lull. lo. 59). rhooo poroaidooo oooolorotoro nobobly oct io tho oopooity
of ouxiliory moo corrioro cod oro tho-oolvoo ooro or loco ocuplotoly
oxidiood in ouch prcoooooo.

lot 1' o Poroxidoooo.

A o Auxiliory oxy'gon oorrior,
D g 'rho poroxidooo roogcnt,

thou
P 0» 211303 —-9 P02
902 o A -———> P «- A02 or
ZPOZ o A ---> 2P0 .- 502
A0: 0- B —--> A0 0- BO

8) 'l'ho poroxido theory of oxidotion ocoounto for tho phononono
of ouboxidotion cud oxygon corrying upon tho ouppcoition thot opontonooooly
oxidioohlo oubotonooo howo the powor of combining with portiolly diooocé-
otod ncloouloo d’ owygoo to for: poroaidoo. ‘rhooo poroxidoo noy thou rooot
oithor with odditionol ooounto of tho outoxidiooblo oubotonoo itoolf, or
with oono othor oubotowo to for. oioplor oxidooo

4) Rolf Riot (Arch. Exptl. Path. Photo. 100, 187-48, 1928)
found thot in tho prolonoo of blood pigmonto ooting oo t ootolytio ogonto
hydroquinono. onino-phonol ond hydroxcbonoono oro quickly ozidiood by otzooo-
phoric argon. io o roducing ogont, with tho ootolytio offoot of blood
pig-onto, hydroquioono or pyroootochol thoroforo my rondor tho ordioory
oxygon octiwo in brooking up tho oclooulor for: to otuio oxygou oo:

. 0
6 t- 02....) Q o 3200(0)

Quin. io wotor oclutioa olmo io oufficioot to blwo guoioou.
looot ooggootod thio to bo duo to tho foo-notion of hydrogoo poruido fr"
tho roootioo of hydration-o cod oolooulor ouygco on

6 o 03 g.) [202 o

w
oinoo gm oloc forno on equilibriun m with WW”;

5) 0n tho othor hond tho worklof Maroon and anroiooo (J. of tho
dhol’lool Socioty Vol. 127 Jam, 1925) provod thot hydroquinono or pyro-
ootochol is ontioxygonio. Thoy provont out’oxidotion whoo oddod in vory
lull quantitioo to outoaidizoblo oubotonooo. It io “plow oo followo:
tho ontioxygm B cuts by decompooing cotolytioolly tho porowido A02 which
rooulto tron tho union of tho outoxidizoblo cubotonoo with no nolocolo of
froo oxygon, with tho formation ortho poruidoo .AO ond BO. Thooo two por-
oxidoo boing ontogoniotic to each other deccnpooo to for- A, B, and aygoo
in thoir originol ototo.

The catalysis Icy be pooitivo, if tho pcroxido BO ottooko tho
oubotonoo A in profcronoo to tho peroxide A0, or nogotiwo it tho cooworoo
condition prtnilo. Tho oquotiono oro:

A o 02 -——-> AO2
A0398 -—-9 5.0080
politiwo ootolyoio;
30 o A ~—) B 0 A0
nogotivo ootolyoio;
30 «0» A0 -—> A o B o- 02

ixpori-ontolly hydrcquioono ployo tho port of on ontioxygon in '

tho owidotioo of bonooldohydo by intorforing with tho fintion of froo

 

-6-

onygon. nmr rooont work by Bmoot in this lohorotcry ohowod thot in
high conoontrotion of hydroqninono, tho Iorooo ood Dufroiooo offowt dooo
toko plooo with gluocoo. In low ooooontrotioo of hydroqoimno ouch on
offoot io not noticooblo.

Hydroquinono and pyrocotochol oro ontipyrotic. fhio my bo
portly duo to tho doprooood oxidotion in tho body, olthoogh thoy oro woll-
hcwn oo noodilotoro.

loorly oll tho obovo rooulto oro bucd upon tho work dono in
vitro oo wt of tho otriking bioohorical oxidation of tho living coll
con bo initotod noro or looo ootiofoctorily by oxporimnto in toot tubco.
80 for thorc io no owidonoo thot onggooto tho ozidotivo prcooocoo of tho
living organiono diffor in ony fundamental way from ohonicol oxidotionl
known to toko plooo in inoninoto noturo. For cxomplo, A Icetonic acid my
undorgo throc typoo of ohongo in the body according; to the dirfororrt con- 0
ditiono: '

1) It my bo oxidiood to a lower fatty acid ,

2) It may bo roducod to a hydroxy acid,

8) Ito ommoniun «it! may be roduccd to on amino ooid.
on oro roodily ammo in vitro; '

1) by hydrogon poroxido,

2) ond 3) by roduoing ogouto oo oodiun omolgan.

In wiow of tho ohm work, nonoly,

l) tho rolotion of cystino to oninol oxidation,

2) tho ovilonoo of o pivoiologicol function of'dihydroazy phonolo.

8) tho rolotion of thoco phonclo to plont oxidation, and to oolo typoo of ‘
aidotion in wivo, thio work woo undortchan. It woo thought thot tho

phonolo light in port roplooe oystine in the oxidatiwo function“

 

 

 

~ .r
~"" 1 44“-!

-__ - ..._—. :—..-_A‘.:-.h. n ‘
. _ (A or”. . .¥!." _

v um:-.-'o.—-w.—.-’a '__‘

 

 

.11 1.;

5.116.)' - ouch-'1.

 

 

Expezimontgl

 

In order to determino if hydroquinono ond pyrocctcchol can bo
substituted for cystino which is oooontiol for growth, four difforont dioto
woro proporod:

Number one has the compos ition of:

Casoin 9%
Salt mm. 4.5% (Osborne ond Kendal, Jo
of Biochom.) 3?, 65731910)
Dextrin 70.65%
Cod liver oil 2%
Hydrogenated cotton seed oil 12.85%
Butter 137.

Diets number too, three, and four have the some compooition as number mo,
except that in number two one per cent of the dextrin is replaced by lobar-
otory preporod oystino, which is ten and forty-six htmdrodths per cent puro;

in nunbor three, one tenth per cent of the dextrin is replaced by hydro-

qulnom; in number four, one tenth nor oont of tho dextrin is. replaced by

pyrocatechol.

In odd 1131011 to the sbow Clio-ts three grams of Fleiaohmanno dry
yeast was gim to each rat wookly, an a swan of vitamino B. Tho Folia-
Locney method for determination of oystino (J. or Biochem. Vol. 51, 1922.
pp. 427) showed tho-611v yeast to contain one and oovon hundred sixty oight
thouoondtho per cent of c reducing oubotonoo. Conoidoring this oo oyotiuo
ond the our-ago food intoko co fifty gram per wool: tho: oyotino fro: tho

yooot amountod to one hmdrod ond oi: thanoandtho per cent of the diet.

 

Bix'ohtto roto ot tho ogo of four‘ooolo‘loro ploood upon oooh
Gilt. Thoy‘Ioro Iopt 1n infltvtdual oogoo and Ioro Ioighod woolly.
Tho rooulto oro u tonal:

 

Avorogo‘Woight
‘Wbokl D105 1 D101 2 D105 5 010% 4
(low oyotino (high oyotino (hydrogutnono) (pyroootoohol)
«about or cutout)
control)_ A

1 55.25 55.51 53.43 58.5
I 50.97 62.25 59.5 52.5
5 62.58 57.77 64.15 51.70
4 62.07 65.27 62.95 61.51
5 72.085 85.41 78.12 75.77
0 85.33 106.12 100.31 95.93
7 87.75 108.37 99.25 95.43
8 89.35 110.45 99.07 92.4
5 89.0 115.95 103.15 94.95
10 100.13 128.8 118.6 104.15
11 121.4 150.95 135.95 125.95
12 128.5 166.3 140.50 132.7
13 128.9 178.25 144.02 152.5
14 139.35 185.88 153.5 185.5
15 150.27 188.1 167.75 105.15
10 145.77 189.3 175.03 155.71
17 153.77 197.97 184.65 156.4
15 155.28 300.5 185.98 155.31

 

in

A

Ff

'—__— fig.— -_.___..__.
._ 4

2.10
100
/q0
Izo
I70.
I60
x50
“/40
1; I30
.5 I10
31/0
[00
610

$0

7 0 /
/.

so — r -
//'

50.
(w oaks)

(1)

(3)

:93 24: s;

(1) Control

(:0 H 18h Cystine
B1H’ydr07u/n one
@fyrocatethol

I1 '
:54 5'6 7 8 q 10 u /2 13/415“, [7187910 .

Oonoluoian

?art of the cystino roqpired for normal growth is roplooooblo 5y
some phenols. Bydroquinone oorvoo hotter than pyrooatoohol.

If tho growth of the control rats 13 considered oo unity, than
the growth of tho roto on tho other throo diets my be oxproasod u, ono
and throo tenths for high oyotino diet, ono Ind two tontho for hydroquinono
diet, and one ond at: hundredtho for pyroootochol dict.

Tho mechonm of the aotion is probably that of tho rogulotlon 01‘
the oxidativo processes.

filth dihydroxy phenols the position of tho hydromy groupo attor-
mino their valuo in metabolism. The barn position 1o proforoblo to tho

otho.

-10¢

(1)

(8)

(8)
(4)
(5)
(6)

(7).

(8)
(9)

Bibliggnm

loch tad Ohm (Mud! (or bioohnuohon Arbolto oo‘ohod. I.
Abdorholdon, Berlin, 1910, Vol. 8. pp. 42-4?)

Abdorhaldon and Worthohnor (Arch. goo. Pfryoiol. (Pflugoro) 198.
415-20 1925)

Goldoohliot (Arch. Ophthalm01.. 1917; x111, 4.7)

Huston a: Lighthody (unpublished work).

Bljlsm & Yorotoigh (Arch. goo. Phyolol. (31115011) 191, 415-28, 1932)

75.11.... (Bor. 1912, or; 484)

0118101! (Bloohon J. 14, 636)

3.1: n1.r (Arch. Exptl. Poth. Pharm. 100. 137-48, 1923)

Ioroou and Dufrolooo (J. of tho Chou. Booioty, V01. 12?, Jon" 1925)

(10) Ooborno .nd 4....1 (J. or B1..h.n.. 37, 551. 1919)

(11) nun a Looney (J. at Bloohom. 7.1. 51, 1922. pp. .27)

(12) Booot (inter thooio, ‘1oh15on Stato Oollogo, 1926)

(13) Clorono (Bull. 8... oh1n. 35, 1198-1206, 1924)

 

«1%.. +11:

1.111.151 d+llét

o. o.‘ 10:0...“h7 J...- A. o. ,I 7'

 

 

 

 

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