Ciba Foundation Symposium - Isotopes in Biochemistry

313 Pages·1951·16.951 MB·English

BIOCHEMISTRY
Reports of Conferences held at The Ciba Foundation
and published by
J. & A. Churchill La:-
TOLEMIAS OF PREGNANCY
Human and Veterinary
LIVER DISEASE
In the press
STEROID HORMONES AND TUMOUR
. . .
GROWTH Ready end
1951
METABOLISM STEROIDS AND
OF
THEIR ESTIMATION
Readyzend
195 1
Other volumes in preparation
CIBA FOUNDATION CONFERENCE
ON
ISOTOPES I N
BIOCHEMISTRY
Consulting Editors
J. N. DAVIDSON, M.D., D.&., F.R.S.E.
L. H. GRAY, M.A.,Ph.D.
s.
A. McFARLANE, M.A., B.&., M.B., a.~.
A. NEUBERGER, M.D., Ph.D., F.R.S.
POPJAK,
G. M.D.,D.&.
c. RIMINGTON, M.A..P~.D.
Editor for the Ciba Foundation
G. E. W. WOLSTENHOLME, O.B.E., M.A.,M.B.,B.C~.
With 79 Illustrations
LONDON
J. & A. CHURCHILL LTD.
104 GLOUCESTER PLACE, W.l
1951
ALL RIGHTSR ESERVED
This book m y n ot be reproduced by
any means, in whole w in part, with-
out permission. Application with
regard tn copyright should be addressed
to the Publishers.
Printed in &eat Britain
FOREWORD
SIR CHARLES HARINGTOFN.R,. S., M.A., Ph.D.
THE advent of an entirely new tool of research is always
something of an event in science. There can be few more
striking illustrations of this than the story of the advances
in knowledge that have been made with the aid of isotopes.
The speed of development of this branch of research is due to
the realization of some of the potentialities of the method
even before separated isotopes were available, and to the
eagerness with which such pioneers as Hevesy exploited the
possibilities as soon as the discovery of induced radioactivity
made the preparation of minimal amounts of radioactive
isotopes possible; it was still further increased by the
dramatic circumstances of the war-time work on nuclear
fission, which brought the technique within the reach of
laboratories in all branches of science.
So far as biological science is concerned it was obvious at
the outset that the tracer isotope technique would find its
widest application in biochemistry; it offered indeed a
method of attack on problems of intermediary metabolism
and biosynthesis which had hitherto been unapproachable.
It was unfortunate, though perhaps only natural, that the
sudden general availability of isotopes for biochemical
research should have led to some rather hasty experimenta-
tion in which the more obvious problems were studied without
deep thought. Such work, although it may provide quick
answers to some questions of interest, is far from representing
the best use of the new method.
As time has passed, there has been more opportunity for
reflection, and the result of this is apparent in the nature of
the biochemical problems that are now being tackled with the
V
vi FOREWORD
aid of isotopes as tracers. All of these problems require powers
of biochemical interpretation ; many of them demand also
new work in organic chemistry, both for the synthesis of the
specifically labelled precursors whose metabolic fate it is
desired to study, and for the stepwise degradation of the
biosynthetic product, so that the process of its formation can
be analysed. Again new methods of isolation of intermediary
metabolites may have to be devised. Thus the full develop-
ment of the isotope tecfinique in this field can only be
achieved with the aid of concurrent advances in more con-
ventional chemical and biochemical methods.
The collection of papers in the present volume, contributed
at an informal meeting by a number of leading workers,
affords as good an illustration as could be wished of the stage
of isotope research in biochemistry that has now been reached
by the process of development that has been outlined. The
Ciba Foundation are to be congratulated on performing a
useful service in assembling a number of contributions which
are not only of the greatest intrinsic interest but, in so far
as they indicate the potentialities of isotope research in
biochemistry, will serve as an inspiration for the further
cultivation of this productive field of work.
CONTENTS
PAGE
Foreword by
SIR CHARLES HARINGTONP,~ D,F RS, D.ir ector, National
Institute for Medical Research, London . v
Opening Address
A. S. MCFARLANE, MB, c.m , National Institute for
MA,
Medical Research, London
. 1
part I-STEROIDS
s.
Chairman: A. MCFARLANE, MA, BSc, MB, ChB
Editm: A. S. MCFARLANEM, A, BSC, MB, c h ~
Metabolism of l*C-labelled steroids
C. P. LEBLON. DP,h D, Dept. of Anatomy, McGiIl University,
Montreal . 4
Discussion
R. J. BOSCOITc, . P. LEBLONDM, . MAROIS, a. HEIDEL- .
. ia
BERGER
High cholesterol content of human spleen
K. BERNHARDPh,y siologisch-chemischesI nstitut, University.
of Bade 14
Discussion . .
D. RI-NBERG, K. BERNHARDK,. BLOCH
16
The biosynthesis of radioactive cholesterol br
surviving
liver slices
S. GURIN, PhD, and R. 0. BRADYM, D, Dept.. of Physiologica.l
Chemistry, University of Pennsylvania
17
Discussion
. .
K. BLOCHW, . G. DAUBEND, . RITTENBERG 24
Studies with deuterium steroids
T. F. GALLAGHEPhRD,, Sloan-Kettering Institute, New York 28
Discussion
R. J. BOSCOTTT,. F. GALLAGHEDR. , RIITEN-BERGK, .
. .
BLOCH
38
vii
viii CONTENTS
PAGE
Part 11-HBMOGLOBIN AND METABOLIC DERIVATIVES
Chairman : SIR CHARLES HARINGTOPNh,D , FRS
Editor : c. RIMINGTOPNh,D
The biosynthetic mechanism of porphyrin formation
n. SHEMINP, hD, and J. WITTENBERGPh,D . Dept. of Bio-
. .
chemistry, Columbia University, New York
41
Discussion
A. N~UBERGEDR. ,S E,EMINH~. G. WOOD,K . BLOCH,
. C..
RIMINGTODN., RITTENBERSG. , GURIN
64
t
Studies mammaIian red cells
on
A. NEUBERGEMR,D ,p m, FRS, National Institute for Medical
.
Research, London 68
Discussion
B. THORELLA, . NEUBERGERA,. WORMALLD,. RITTEN-
BERGP, . L. MOLLISON .
82
Preliminary investigations for a study of energy utilized
by the surviving fowl erythrocyte in hsem synthesis
C. RIMINGTOPNh,D , Dept. of Chemical Pathology, University
. .
College Hospital, London
86
Discussion
D. SHEMINC, . RIMINGTONH,. G. WOODH, . A. SLOVITER 89
Iron metabolism in pathological conditions
A. VANNOTTMI, D,C linique MCdicale Universitaire, HBpital
. .
Cantonal, Lausanne 90
Discussion
A. S. MCFARLANEA, . VANNOTTKI,. ATERMANJ, . E. FALK 94
Part 111-USE OF TRACERS IN THE STUDY OF
BIOLOGICAL EFFECTS OF RADIATION
Chairman: SIR JOHCNO CKROFT, FRS
Editor : L. H. GRAYM, A, PhD
The modification of X-ray sensitivity by chemicals
A. HOLLAENDEPR~, DG, . E. STAPLETOaNn,d W. T. BURNEIT,
JR.,D ivision of Biology, Oak Ridge National Laboratory,
. .
Tenn. 96
CONTENTS ix
P' AGE
Discussion
L. H. GRAY, A. HOLLAENDEMR. , GORDONB,. E. HOLMES,
H. A. SLOVITERA, . S. PARKESJ,. F. LOUTIT,L . F.
.
LAMERTON
109
Effect of X-rays on nucleic acid and protein synthesis
in
the Jensen rat sarcoma
BARBARAE . HOLMESP,. h D, Dept. of Radiotherapeutics,
University of Cambridge
114
Discussion
R. J. BOSCOITB, . E. HOLMESG,. B. BROWN.
120
Radiation dose in tracer experiments involving auto-
radiography
S. R. PELC,P ~D,R adiotherapeutic Research Unit of the
Medical Research Council, Hammersmith Hospital, London
122
Discussion
L. F. LAMERTOSN. ,R . PEW,L . H. GRAY,A . HOLLAENDER,
.
B. E. HOLMES
136
Synthesis of deoxyribose nucleic acid and nuclear incor-
poration of as shown by autoradiographs
ALMAH OWARDPh, D, and s. R. PELCP,h D, Radiotherapeutic
Research Unit of the Me.d ical Research Council, Hammer-
smith Hospital, London
138
Discussion
C. HEIDELBERGERA,. HOWARDC, . P. LEBLONDG, .
POPJAK, S. R. PEW,G . B. BROWNB, . E. HOLMES,A . S.
.
MCFARLANE
148
Part IV-NUCLEIC ACIDS
s.
ChaiTWn : A. MCFARLANEM, A, B.Sc., MB, ChB
Editor : J. N. DAVIDSOMND, , DSC, FRS.ED
The biosynthesis of pyrimidines in uitro
D. WRIGHTW ILSON,P ~D,D ept. of Physical Chemistry,
.
University of Pennsylvania
152
Discussion
E. HAMMARSTKE. NA, TERMANA,. NEUBERGERD,. W.
.
WILSON
162
Studies with organic- and bio-synthetic nucleosides and
nucleotides
.
G. B. BROWNP,h D, Sloan-Kettering Institute, New York 164
CONTENTS
X
PAGE
Discussion . .
C. HEIDELBERGEE. RH,A MMARSTGE.N B, . BROWN
171
The use of radiophosphorus in the study of the nucleic
acids
J. N. DAVIDSONM,D , D.S C, FRS.ED, Biochemistry Dept.,.
University of Glasgow
175
Rate of synthesis and quantitative variations of the ribo-
nucleic acid during the growth of a culture of Polytomella
coeca
R. JEENER,D ept. of Animal Physiology, Universit4 Libre
. .
de Bruxelles (presented by D. SZAFARZ)
184
Discussion
G. B. BROWNJ,. N. DAVIDSOCN. ,P . LEBLONDD,. SZAFARZ,
. .
G. POPJ~K 188
Part V-PROTEINS AND AMINO-ACIDS
Choirman : A. s. MCFARLANEM, A, BSC, MB, c h ~
EditOt : A. NEURERGEMRD, , PhD, FRS
A method for the evaluation of the rate of protein synthesis
in man
D. RITTENBERGP,h D, D.e pt. of Biochemistry, Columbi.a
University, New York 190
Discussion
. .
A. NEUBERGEDR., RITTENBERG, 201
Turnover rates during formation of proteins and poly-
nucleotides in regenerating tissues
E. HAMMARSTEMND, , D.e pt. of Biochemistry, Karolinska.
Institutet, Stockholm
203
Discussion . .
D. RITTENBERGE., HAMMARSTGE.N B, . BROWN
211
Synthesis of phenylalanine and tyrosine in yeast
K. BLOCH,P hD, Dept. of Biochemistry, University o.f
.
Chicago. 213
Discussion
R. BENTLEY, H. R. V. ARNSTEIN,E . E. POCHIND,..
RIITENBERGK, . BLOCHH, . A. KREBS,H . G. WOOD 224