(SANITIZED)UNCLASSIFIED RUSSIAN-LANGUAGE ARTICLE ON FOLIC ACID METABOLISM AND AN ENGLISH-LANGUAGE ARTICLE ON 4-AMINOANALOGUES OF FOLIC ACID(SANITIZED)

• Document Type: CREST
• Collection: General CIA Records
• Document Number (FOIA) /ESDN (CREST): CIA-RDP80-00247A003600070001-3
• Release Decision: RIPPUB
• Original Classification: C
• Document Page Count: 12
• Document Creation Date: December 27, 2016
• Document Release Date: February 18, 2014
• Sequence Number: 1
• Publication Date: September 11, 1964
• Content Type: REPORT

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Declassified in Part - Sanitized Copy Approved for Release 2014/02/18: CIA-RDP80-00247A003600070001-3
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0 METABOJIIIME 40JIREBOR KIFIGTIOTIDI. II*
YCJIOBHH 0PMHJ1UP0UAII11800JIIIEBON ICHCAOTIA**
It CJIABH1( i b. IdATOYJIKOBA
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6mem1tate, i 11-a .4a6opossopiat stimuiustu eloymperesux 60.444m418 IImc p.4
oey0apcswemoorit imaispenwasaani 6o.sesugs, 17 pasts
110mm:to I penantuns 18 nuaapn 1954 r.
Aatopi pa8pa6orann moroinsy 6ynamoso4 xpomarorp8488 u1op8H08
BOARMx pacraopirenFri H koAnnecrsemmoro onpenenennn Opium-
+onnesoll nwc.80884.
riierwamm, ypomamorae n 40068.1171n1noranrr9posan Kmr,a0Thi I me-
(Konbee pas y88.88romairr ko.ruellecrio lopmantonnesoll limcncrnd ,
06P6dyinleici 110 elmuutesoll MINIOTSI 8 illITe80980M romorenare.
ricrinama npons.ineren I anaapo6n8rx ycnoannx 8 me 895.18)-
?nova npn sapo6Koae. ibopiataranersimn isopulinusoragnahowm Ns
&TIMM ea o6peaosamee 401)111140.11118804 K8C80T111.
B npeamayumee coo6nommm1 6h1,1 ony6,ammoaam na4ieHH1111 Hain 418KT, TTO
npm mamy6aarat romoremaTe ma Ilegelin mpwebl c otonnomot mmcaoroll o6pasyer-
cm cameaexemo +nlooperuispyieniii iiera6oanr, noroptall H8 ocmonamwm exert-
rpoe 6m.3 maemr14omumpoeam max 10-4101)KM.40.1111e8111
patiee Payems, ma ocmcmammm maymemmm mpmeux ero
Neway 0,1X .HC1 ii 6yrRionoli, 110.narin, o 8TOT MPT860.111T TOMAOCTICI
C fopimatbdamesoll KINCJIOTOIL BeCiata BOpORTHO, 4T0 8T0 sentecriu,
Plume xio6otlarrmane 4agamonormeecamir aeiteramem, /111H caw Limner ma np0-
ZeitHOBlii aNa6onnem, Nam msaltetcm apeatuecTmenummom Two 06pa8011141Valli
aellioSopitita, CHHT88 moroporo Me +oamesol IMCJI0Thi B oiworemaraz is
xypnaolk ine?reim ioxasaa Hilicoa84 trpm noacours wwspo6monormgoemmx wroa
c Le eitrovorum. B macTorrate. pa6crre 111,1 maymaim ycaoamm, npat
NOT0=Ipe anyeren 4)opirma.o.ameaam mmcaora, 4TO rips 6oabwom atiVIONIMM
prom seulecrea WIPE 81860.1118118 &Limos Nor.no 6w arm% memoropur ceeaexam
o peryaxautommuz Nexammamai CallTeei 6eamosaa sewers B opran14814aZ.
esimpantearranatas vans
liarepiaa
tOoFasu.,s-Ll&spoma.atioc," $OO err L-rearramese pacrsopnaocs B 12 ma 80% nypanbourall
uncnorm, i pacrsopy np1038aninoel, 13 ma yncycnoro amrnApuma. Terneparypa ups
91.011 camonpOnasenbao nosatusanacb no 45*. 4'OpM841190801iilan CMG, OCT8BAIRA806 ero0r8
? Coo6nteise 1 rm. wypnane Chem. 184 47, 1616 (1953) i i prini aftypnane 11, 393
(1964).
?? Sian? 'panee ony6nnmos880 B tetyplaze MOM listy 48, 765 (1964).
??? Moan ononmannot ;vroll paiorri Bopem i Vain mas ?nom= aoarteine 8TRT
Olen upionAtrr Ana .opanta-L-ramaxilt T Wt. 118-1W, Ann tOopinn-1.-iiiorarnaann
(nosynennor0INWM nyrem) T. u. 185',
1032 CoLleetioe Oiseelioalov. Obses. 00gailtol. VOL 19 (1894)
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Declassified in Part - Sanitized Copy Approved for Release 2014/02/18 : CIA-RDP80-00247A003600070001-3
9 Aetna,&imam .Sixese?oii NUC.40J114. //
I" *Lae, saves neperonnaaes ups $W, a weassuilles e=jacrupaaes a meat mope&
aserrous (2 1). Hpa nos staxpsessiusisossusaases au %MTh asonpopaarupoaas-
wore ramoriussua, itoroptall .4win.iposwu.ica. Hoene zusaapnassixa sasyyme ia carpi,-
aneraruoro Ssabrpara wartime'. 120 sr spuessams. T. sta. 112.
(173) shruicaeuo: 16,20% N;
salamis: 14,92% N fRi.eakilanu) .
foopAssi4-L-uaoemontamtu4:*** 250 sr I.-assay:wants& paersopognoes a 10 ma 80% itypa-
asaruoll wcaont, K pacrsopy npir6auasaocs 10 ma yucycnoro auritatna. Hoes, rbro,
Jim( rewneparypa sot-rums 45', pacrsop oixams2a.newAo sointarnoll resneparypsi I mule
Cross/Nu a release 1 xraca lloopintasrposurruas emca neperousaaes. sips SC . Ocrassndlon
airport pactsopsaen a cnspry a neboasnras viers uenpopeatiposastuero ass,asausweroca
arsornrrralonta crilkinarpoestwasacs. fires sunapirsanws enurresoro pacrsopa a samyyme
nonynancs cspon, nocrenenuo sarsepaessanne a upscraaasi.1Hpir pacruparus
*epos (upon aaraspnesiut a sroassarsie upsersaauxu. Burro* 70 Mr. T.
128?
C.?H ?0,N, (175) ahrrucaeso 11,10% N;
lialkneuo: 16,01% N.
06a seeneersa we saw? pumps e innerkwireour. tips ix 2w.liC1 iv* 100?
spurning ammuss s rmoraszsoaux piencrra, Hamm? soma? 20Kasart. pamszirreamitoll
6yamacmoll xpseskrorps.uell.
Oup.sedosebdshowonsaparea suesesse noarraaaes no cnoco6Y. Sopess u trammel' !tyres
aaxy6*tuis ebrrsouss Na Elegies's IMMIX c rim/amazon. Howrolias an Orrirni, all.f, ?mum?,
se Aucrorau soasreecrsemsoll possums racTemina U W10/40a, ykaaaRatiii truss saropases
a ax opeasapirreabliom c00604ets11". Tam Ham nay He y9unoci. maim. 6osusnoe soauluterso
aleupopearsposastnero nepyyTITOm, TO Kw MAMBO 4110plialla0110rniOTapOlyal
micnoTy Or rlICTICatal arms npenaparusnoro uosoloopess a flymassiol mime a 0,05s age.
Tarnow 6y4joepsor psersope pH 6. Ms nOariami Tamils o6pasoat nponymr, wecouepatasmull
aeiecn,uausaux peamuss3 nava.
06.111iMILS suesouss ourulaascs stro,lotd, onacaustat a upeasnymes coo6upusa, we
IlialeTota Kosrpoaaposaaam, npu noisome 6ybsuusoll sposarerpailsiu.
lioaultecriesnoe onpesenesse 4flopsumpoasenolt sucaorst
t?opwsraponiesau ime.a0Ta oraugaerren csabnot cusesesessal tisnoopecnennael, a oso-
6eusoers a UtORONH011 epene, sampan aser e0a140)KaOtTi rips npameaealii noax0aaalar0
Ta6aima 1
Iteaaganid Ft, mosoropsx wrepusos aps xpomarorpa.ant a SIOANWI paCTOopax
Ilreples I 0 ,1H.HC.1
0,1x.NaOH
suers?
pH I
I *Asir
04,6,5
4poe+ar
pH 7,7
0,5?
II Tomlin - 6 - ma p-
6oReambaerro .
nTepwnsw-6-Naprlo
noose swam* .
0,62
0,52
0,45
0,63
0,26
0,60
0,45
0.4
0,38
0.61
0,42
0,61
6-Merstaurep lemur
0,76
0,53
0,48
0,53
0,51
0,55
.11edbunrrepus
0,30
0,50
0,24
0,29
0,201
0,35
Coopiniasepoasessui
MICAOTI
0,78
0,93
0,77
0.2'1
0,34
0,87
4ISSTResan Rite..119ta
0,63
0.32
0,5$
0,45
0,50
alopnan qpxocfl. Xiat. PafScrr f. 19
1033
Dnrf - qnniti7Pd Cony ADoroved for Release 2014/02/18 CIA-RDP80-00247A003600070001-3
Declassified in Part - Sanitized Copy Approved for Release 2014/02/18: CIA-RDP80-00247A003600070001-3
(:AH/eat, Manioymeoen ?
unnapaTa onpeAeoarb ;to 0,02 ?Om. ilpamoe n.aloopoiderpagecioe onpeReneano Soopan.n-
noaneoollk KIICAOTIA w pacTsopaz, noxyveualwa Houle yRa.iesua Genaoa NH IIINHy6auxotiwhoi
mecca, Hecbma meaaRemao, Tea max a Teveinie waky6awma 06paaprertn Apyrie .aioopec-
Rappotame irrepanaosbie meTa6oaaTu, a rips iamopemai 4)afoopecReaRra aarreppapytte
TaK)ot meaTaa Saloopeateattia 4oluntHoa. lipowe Toro, HeaoToptaa semet:Tha, upeaca?
acero Neopupearrposaautan tonmesaa Kar,.urra, racaT 4).THoopecueawno. floaToogy 6bia
paapa6oTaa meToA t;pakin.aoll xpomaTorpackam uTepamos, RaaaHma 8031110HMOCTb Eumaoro
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xposaTorpailiant Ha ymare BaTMUH J4 1 IlpH IICHOZIAORAHNI BOAtibla 6y4wpinax pacTaopoi,
I HOTOphil xopoiao MOWN? paMealiTis X1 nTepaHoa. B Ta6inote 1 upigae,aea oftop
se.aatHau ftp aeaoToplax cauTeTagocanz, irrepaaoa a paaamx 6y4)epakax pacTsopax. (Vasa-
necitaa cywocTb aT0i0 lflLJ 6yransuol ipomaTorpa.am aoRtimax paeraupama mexaseetna.
alpupTei, paaReawatual 1poilaTo1pa4nmacan aposasoamae eaamtaaoaoa KaGIOTIelso,amesaai
panraopama, upennonaraer, %ITO 5paara RPacTayeT a magecTiie aomoo6menaina.
flpic nominecivenaom onpunciatos MW nocrynana Taoism o6paaom, 4TO OVILHOffielik or
o0paaen a KonamecTaa 60 n.n mananbtaanca Ha gerupszoturramerponyio nonocay 6y-
Nara aa ?pax 11no cirrupei meirraz. llocce paaAe.newaa a 0,6% pacraope yrnemicaoro
awrpica icrrnpurtma a VV-nymax soma 4)opman.onaesoll xacacyru Bapeannianacs a a np0Roa?
weave 2 sac. npdabiaanacii 10 inn yr.nemacrioro aarpan a con6onne ups 886HaTliaatilla spout
OT apemen' PaCTHop Sarmirpoalinca a441100peCHHallaa a:1140pRafieb as 6?KMIUMOUCH0N
asapiamor cneterpofoTomerpe DU c apacnoco6.7enian xis assepenua cliapopecuenviai.
Bum.* nepaonatiaamioro 1eT0911Ke. enema a anAe anewrpatiecao$ aaasawmi aeHaaallaillen
MU 11041be0Baalleb irryTwoll Rama**, 1 Ile of enearpa rips oomouas saa eastakaabworoimablpa
^ sumapare anarwaapoaeb nograRaioul lm aa hau 365 ps. Corpam v
eonnae 110-arla
IICHaleqa:111Cb Hp. Homouas wearoro SanuTpa, acraaaeauoro aepea isYroaaanewrom. 06-
paanka a:wept:Ian, no cpaanenamo co cnaaAayrroa 10 sax 20 Lr ourrirrimecnoll
itioanesoll micsorm, notopaa Tannin no;thepranacb xpomaTorpa.am a npomisaanaio
Toro, gTo6bi 61a/a1 amnoaaeabi ycaoass oniaTos aaaanauponaamaz o6paaRoa. non acnoab-
aoaaaint eTaaRapros 10-20 la iLoA Kaam6posomaba }(paaoll (manna-Tea :uivallawas.
?HUTU eableamaau
B 6onbine6 gacnit onfrgroa nuay6awia nonaepranics 2 ALT1 60?)?,, neganonnoro roaoreturra
a 0,9% NaC1 c 0.2 ma pacruopa Beniecraa, Banname noToporo as ansaiaaTirlecaro awning
aarmaoci., a 0,1 an parreopa tbonaeaoll mac.aoria (.tS mr) a apo6ripsas BOA weans mamas
a rename 22 vac. tips 26?, a Teaa0Te. 113 o6paaRoa saran yaaanaca knois 0,1 RA 70%
paCTIKIpa TplIlLeOpOyHeyellOa Haea0T11; HOCae eTO oTaearrpi+yriposanan tpax.nopo-
yacycaaa HaCAOTEi yRansaach Tpoemparmaa alaanTbiaaaaeat a agpap (I pass no 4 ma).
06pa6oTaszhae Tumid o6paaom o6paaum ipomaTorpa4Hiposaaner a ansuntaapooanach as
.0p111U1.0AlleaylD HICAOTy. Hp* aapodaoas a aaaapo6moaa o6pamai iulay6apo-
yammer azoi:s5a0 a cocymmax aapflyproscsa: seanOmmoi arsocilaipe Hse.nopoRa, aaaap06-
Iame Ria awxy6apoaaanca a Tpy6mai TrilSopra a ansoupape aocopoaa.
Peilyal.TATIA R 11X olkyamease
,1.1114 yc?rakormemin ycamoill peamput doopmumspoaaann tioomfesolk sur-son4
6bulo ueo6xdAmmo H&TM IacTotnik1KH 4)opuitabao3 rpynma, a ?UMW acToinfax
aoeprazp.Ju Toit peamrxm. Mimi mcupo6osa.na tom senlec.ra, OTHotifTe.11600
HOTOIMIX R8DOCTHO, TO ORR Rorr 41yHHI1n0HaposaTb xastecrae Aoltopon
Mei1labH031 rpynnu, upen(Ae acero KeTMOHNH, copal R IoJLKH. oxiaamo Hi y oa-
*tyro NB BTRX seulecTB He 11pOR3RROCb cyntecTaennoro eT14111yRAIARORHOTO
nekirraan rIB o6paaosanne .oparamloonseaolli micaona. Tomato rimerwAsa,
FIR.IRIDWRRog a opranmamax npa R8130CTHUI ycnoammx RICTOTIRMICON Kellum/to*
rpyrrnu, 0HaaancH cnruyairropou 6aocaaTesa 4)opganfoameacIt macacrru.
.0TROCRTeZbli0 racTamula yore pOn0J1bH0 auuo RalleCT004, WO OR noaumae?
Honwiec-rao,immpoomonoragecith yaoanuOt (tooasteaolt xacaoru a netremouniz
rouoreaarat. thrum neKuropui airropoa7.? c ITICT11*4110M, meienbru C14
notcaaa,am, wro yrnepoA, naxowitalicst a itulmasonbaoar 101x.ne rue-moms
1034 Colleotion Csechoslov. Chem. Coalman. Vol. I (1964)
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Declassified in Part - Sanitized Copy Approved for Release 2014/02/18: CIA-RDP80-00247A003600070001-3
0 mema6oAsuAse 00.410?014 Ximaombt. II
rtanomensu 2, uepexotorr Apyre eoettzwestut (Ratipstuep, 11 upearrtitt,
Ramat, ceptin) 8 tome uteranbaolt rpymmt u ?matte eT111,011ITCH COCTIINHO*
?acruto nypmmosoro mtpa. florroary aroma() 6wto 6ta npemonarrn, 4TO
TICTWARE1 mower 611Tb IRCT041111140814iopmantmott rpyzma trim dapirmatiposatom
+oamesoll POICJIOTIA. 118.1101 omt 110141881111, RTO rmer?Amt ypeamtmweer H04111-
118CTIO tioopinta4loamesollt MYCJIOTEJ, e6paapouteitcx Ma Somse?oft HilevlOTIA
Pse. 1
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romoreasrax
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4,00
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3,84
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Ceopiatit Mezorz. Xis. Patio? r. 19
103$
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Declassified in Part - Sanitized Copy Approved for Release 2014/02/18: CIA-.RDP80-00247A003600070001-3
CABALLX,
H ittil48HORHUX romorettaTax (pile. 1 pile. 2), II 1104TOMy mown() upe.utn-taraTr.,
9TO OH HB.afteTCH HcTOIIHOHuil Ann 06paaottainut titopowwabiti.di rpyttimi KooN.
tieeTHO 1191(6aBaeHHur0 THCTHAHHa OKHablHaeTekt Hpftmo 1ipo1Torp04,11;tablibell
mo.initecTay co6paa08ainneitcw 4)0pmit40.1Hesoil HHOJIOTb1 (pile. 2),
JJf Toro, riT061.1 /MATH 14P.T86011HT rucTitiraFta, woTophtti wenocpego-raeHmoo
AlieT 4bopmwthiipo rpynuy, MM TaJ1150, yeT8HOBliTb, 6yAyT iii OHH:HABBTS.
vTithiyARI.KHOHHOe ;tette/rime Ha oGpaaoaanne 400pM11.11410.1HeNI4 HHC.loTI4 flitf the enzymes iormylating the tetrahydrofolate, the
system formiminotransferase cyclockaminase only was
inhibited by all 4-arnino-anakigues tested, but only con-
centritions 10 'M caused the 50% inhibition of the
enzymes. As tested by the LineveasPer-Berk test, the
0.t._ BtacLar, Bwchem. J SS, 445 (1954).
S. Fsf , Chem. Zentr. Ji, 9610 11961).
? S F. Zakazawski and C. A. Nicent, Biockim. biopsy,. wets IT,
425 (19661.
' G , Fed. Pmr. 17,744 (1+44).
i 14 Ferias and D. M. G , Nature 81, IOW (INC.
' 54. J. ()swam and F. M. fluatireaates, J. biol. Chem. SiS, tee
-- 0968).
K. SLAVIC V. SLAVICOVA. and Z
Commun. ts, 19411 f 1960).
? NC J. 0a9oac and F. M. H
646 (1967).
? R. L. BLAIELIY, Biochem. J. si, 316 (19661.
m Y. HATIII, 11. J. ?MOOCH. L. D. K.v sad
J. biol. Chem. 337, 637 (1967).
G. R. G , L. J4.12cfcaz, and M. Sit.vaitu?s, hioelsaia.
bwpsys. Acta 1r, 509 i1950).
H. Taatut and L. YPIGAinalli, J. btol Chan. far, 1880 (11611).
" ti_*kay-tit and V Maroutsiu2.4,c9.11. Czech. Owen. Commus.
"19547-
KOLe?II, COM. COMM. abliMi.
, Biockisn. biophya. Ada if,
F. M. Humanists**,
Si PIET/Its I) 14 , .ooi. Caen. Ill, 395 (1117).
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Declassified in Part - Sanitized Copy Approved for Release 2014/02/18: CIA-RDP80-00247A003600070001-3
114
Tab 1
breves comintitlications - hurze.Mitteituttigen.
k-iiesautirria XV1118
Ihe inhibit on 01 some enzyme systems con.erfine I if 11110 cuenzyntatically active derivstes by 4-aintrioanaloques 01 folic
Enzyme
Method of activity determination
Antimetabohte
II iii mirtatiobtes
I.4. 01111
1k at :142 nip,
[mature iaii imidAlolilir
tetratoklrofoi.tte
ia
VI lodrhydrase
us the incubation
derivate of I
I 4
Aminopterin
n. intubiti )n at U 3 Jo Its
N"-Formylaminopterin
. inhibition at 0 5 10-I AI
N"-Forinyltetrah vdroaminopterin
1%14- Form y heti ahvdroaminopterin
43 10
202 0
0 76
Tetrahydroaminopterin
143 ltr I
(34t1
2 38
M-Meth ylentetrahydroammopterm
i 10
477 0
1 78
N"-Hydroxymethylammopterin
N"-Hydroxymethyltetrahydrosmiriopterin
Trihydroxymethyltetrahydroamitiopterin
, tio uttuLawn at u s 'Ws Al
N"-Methylsminopterin
4.6 il) 4 26b 0.43
N "-Meth y ltetrah ydroamiliopterin
no inhibit tin at II 5 lira M
Folic acid reductase +
dLhydIofulic acid reduction
Determination of dinotable amine after
decomposition of tetrehydronnto ionised
with acid
8 6 ? 10-' 0.0036 0.000016
3 5 ? 10-400167 0.0000724
4.3 ? 10-'
0.19 0.00062
t' 2 ? 10-6 2.3 0.01
10 ? 10-4
.5 ? 10-7 046 0.002
0.202 0.00088
1.19 10-4
0.526 0.0023
?
7.6 ? 10-a 0.336 0.00146
2.0 ? 10-4 0.885 0.00325
6.2 ? 10-4 0.00275 0.0000119
? I. Molar concentration of the inhibitor causing the bli% inhibition .4. .41/8olute omcentration of tbe intub tor causing Ow 60%
ininhition. :1. Molar inhibitor - substrate relation.
Enzyme
Method ot 411 IIV
An till tabohte
A nil ii pt trill
NI6- I oT7t11 la ini noliter Ill
N" 111011, 'tett
pterin
10-Form vitet taO VIII.a
pterin
Tetrahydroarninopterin
N4- la- Methylentetrahydro-
aminopterin
N"-Hydroxyniethylanuno-
pterin
N "-H Vdros yrneth y 'tetra?
hydroaminopterin
Trihydroxymethvitetta ?
hydroanunopterin
N Methytarninoptei in
N"- Met ti y Itet rahydroaniino-
pterin
Tab II
Senile akil)laISX I Uviioayinvthylietrahydrofutic
bvdrozyinethyltetrahydrotolic acid ,lith Ydroffeliarie
atd dehydriigtinase
I
?
1 8 lir' 79 11
32 10-6 142 0
6 9 10-6 300
37 lir 6 165
7 3 10-4
414 10-6 139 5
3 25 01 14 1
:1
Fonniniinotraintiesse+
cyclodearniesse
1141. find, dr. ?t ii after lit 114 deprotemitation
ItSI'
0.2i)
0 109
0 (121)5
II 911
o'(44
84 2
111 4 1113 11
1.7 10I 737
22 6 97
74 10' 33
$3 ltr 3h1
1 28 111-4 14 0
a H._
t, 549
u67
0.48
0 0634
0.0209
0 247
0.214
It
$
o7 U
122 0
104 0
0.43
0.78
0.67
no inhibition at 0 t? 10-4
3.9 .10-6
8 2 10-4
1 86 ? 10-4
362 10-4
25 ? 10-?
70 ? 10-4
5.85 10-1
173.0
365.0
82.6
160.0
1130.0
312.0
2600.0
1.106
2.34
0.53
1 02
16 1
2.0
16 7
6 I. Molar concentration of the inhibitor causing the So% 'II 2. iibsi ALIO. concentration of the inhibitor (Jitii ill cauMnIf the 60%
inhibition. 3. Molar inhibitor substrate relatioli.
inhibition may not be of competitive nature The enzyme
leucovonn-cyclociehydrase was mostly inhibited by the
structural analogue of leucovorin, but the inhibition was
of the same order as in the case of the formimino-system.
Al for the hydros vmethylating systems, the mano-
metric method for the serine-aldolase determination de-
scribed by BLAKLEY 4, appeared to be unsuitable for the
inhibition studies. Thus, the activity of the hydroxy-
methyltetrahydrofolic .acid dehydrogenase was deter-
mined with serine and tetrahydrofolate as substrates
The activity of both the serine-aldolase and the dehydrti
genase has been determined in these experiments For the
determination of the dehydrogenase activity only, N4 a-
meth% lentetrahydrofolic acid was used as the substrate.
From ilie comparison of the inhibition of both enzymes
tested, it can be concluded that the serine-aldolase may
not be inhibited by lower concentrations of the inhibitors
than the ciehydrugenage.
In two enzyme systems tested, it was found that the
structural 4-amino-analogue of the substrate was attacked
by the ?myna. The enzymic formylation of aminoisteria
into N to-formylaniinopterin was deecribed earlier. In the
course of the studies on the serine-aldolase, the conversion
K TosAllova, and V. SLartitovA, Coti. Caeca. Caen.
tot-moue. 1367 (19641).
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ti 1141 Bre,' connnincutoro line( Reports ? 115
a
1 2 4 6
The chromatogram of the incubation mixture of seriue aidolase from
Pesos liver with totrahydroaminoptenn (0.5% sodium carbonate,
ascending technique).
Ihhopirs: 1. striae aldolase ?-(-? tetrahydroarninopterin t
5. sample without enzyme. 3. sample without serine. 4 vtithetic
11*-14-usethylentetrahydroarninopterin. 5. the mixture of sample I.
with the synthetic N*?"-rnethykntetrahydroasiiinoprerin.
loom : a) light-green fluorescent decomposition product ,,f t,?tra?
bydreaminopterin, probably 2,4,6-trtaminopteridine, b) tetrahydru-
aminopterin. c)1,11-0-methylentetrahydroaininopterin.
if tetrahydroaminupterin into Ni-o-rnethylentetrahydro-
aminopterin was detected by means of paper chromate-
why of the reaction mixtures. The product showed
identical behaviour with that prepared by the non-
enurymic hydroxymethylation of tetrahydroarninopterin
by low concentrations of formaldehyde. However, the
dehydrogenation of the substance mentioned to the
148-"-methylen-tetrahydroaminopterin could not be ob-
served. From the results presented here, it can be sup-
posed that from the enzyme systems of folic acid turnover
ths hydrogenases are most strongly inhibited by the
4-amino-analogues of folk acid derivate.. Even the hydro-
genated and N? or Nie substituted 4-amino-analogues,
which are much less active than aminopterm or ametho-
pterin themselves, show the strongest activity on the
folk acid hydrogenises. However, in the case of the last-
mentioned substances, the inhibition of the hydroxy-
seathyltetrahydrofolic acid dehydrogenase should be con-
sidered.
The results of the toxicity determination of the above-
mentioned 4-amino-analogues for mice" do not agree with
the enzyme inhibition observed. Thus another mechanism
of action might be supposed; i.e., the interference with the
natural folk acid coenzymes in the single carbon transfer
reactions. The inhibition of the thymidylate synthetase
and the glycinanainoribotide and aminoimidazolcarb-
oxanside ribotide transformylases will be reported later.
Zasessiseeatessiiieg, Der Einfluss einiger 4-Aminoana-
login der coenzymatisch aktiven Folsaturederivate auf die
Enzyme der Folsiureumwandlungen wurde verfolgt. Die
Market* Hemmung zeigen alle 4-Aminoanaloge auf die
Hydrogenise der Folature, wobei die Hydrierung des
Pyrazinringes dieeelbe deutlich vermindert. Eine milssige,
jedoch deutlich schwlichere Hemmung von nonhompeti-
fiver Natur wurde bet der Hydroxynsethyltetrahydrolol-
siuredehydrogenase, Forminunotransferase und Leuko-
vorincyckxiehydrase festgesteUt. Welter wurde die enzy-
matische Hydroxyrnethylierung von Tetrahydromnino-
ptenn durch Serinaldolaseaus der Tau ben le bar beobaChtet.
C Vine, SLAVIKoitri and K. SLAWIC
/within ol Hematology ami Laboratory ol Protein Melii-
bol:sne, Charles' University (Prague), 8. November 1960.
" K. Morvt K A and J. &knees, in Press.
Establishment of an Epithelial C.0 Strain
from Calf Liver in Continuous Culture
Calf liver cells were isolated in September 1950 for
various researches in the following way. Fetal calf liver
N% as minced and the fregments were explanted on glass
without plasma in a culture medium containing 25% calf
serum and 0.5% lactalbuinine hydrolysate (N. B.C.) in
Hanks balanced salt solution 1. The cultures were in-
cubated at 37?C. Media were changed every 1-3 days.
Subcultures were made after about a month by trypeiniz-
ing (0.5% trypsin in a salt solution deficient in Cu" and
Mg). In the beginning growth of the cells was slow, but
after the 5th subculture (March 1959) the growth was
more regular, quicker and clearly epithelial as a close
packed pavement epithelium. Cells frcim various explants
were kept in culture. In the early stages most explants
often formed epithelial cells, but after prolonged culture
the cells were fibroblastlike. One of the subcultures how-
ever grows as a sheet of cells on the glass wall. After
establishment of these cella in continuous culture the
serum percentage of the medium wee reduced gradually
to 5%. The doubling time for this strain is two to three
days and the mitotic Inds% 2-3%. The shape of the cells
from this strain (KaLe) is polygonal (see Fig.). The mean
nuclear size, measured in ? culture fixed with formol-
alcohol-aceticacid and stained with iron hematoxylin, is
16 iy . (The mean nuclear sift of liver tissue filed and
stained on the same manner is 7 There are some
'giants', 6-7%, whose nuclear sire varies from 23-42 P.
The number of nucleoli per nneleus varies from 1-7. There
is no relation between number of nucleoli and size of the
nucleus. The number of chironimomes is 70 2 (normal
fetal liver cells 60). The cell* on the photograph were
fixed and stained with 2% AgN051. between the cells a
'cement subetance is clearly visible, Which is stained by
the silver. (Cultures of cartilage cella, stained with AgNO,,
never gave gaining of such 'cement substance although
some aneuploid strains grow as epithelial sheets as well.)
The mitochondria of the liver cells ate mostly spherical,
some are filamentous. The pliplina of the liver cells hued
with alcohol 70% and stained with the PAS reaction is
clearly PAS positive. Pbyekilogically they are thin liver
cells. Up to now it was impassible to cultivate this KaLe
strain as separate cells in saeptualos. We tried it with
shake and stir cultures, but alwaye Woups of calls were
found. It is probable that the colln am held together by the
cement substance. Biochemical ratiarch on this strain will
be published elsewhere.
J. Print., Colt one risme Ceder* (S. sad S. Livieestrew Ltd.,
kdenburgh and London 11160).
B Ito a, a is, Mshreehreiselre Teshmik lith dd. (11 Oldsaboimi,
nuneesii 19411).
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