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Book Review Relationships between Structure and Function of Cytochrome P-450ЧExperiments Calculations Models. (Series Frontiers in Biotransformation Vol. 7.) Edited by K. Ruckpaul and H

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BOOKS
Mass Spectral and GC Data of Drugs,
Poisons, Pesticides, Pollutants and Their
Metabolites. Volumes 1-3. 2nd edition.
By K. P f k g i v , H . H . Muurer and A . Weher. VCH Verlagsgesellschaft, Weinheim/
VCH Publishers, New York, 1992. XXIX,
4224 pp., hardcover
D M 1290.00.ISBN 3-527-26989-4/0-89573-855-4
In clinical toxicology the diagnosis of
toxic symptoms requires that a poison
must be definitely
identified froln the
x imCLr munr
various possibilities
Mass SPedral
and GC Data
in a very short time,
so that remedial
pd1%%?~~%2
kund
treatment can begin
1
as soon as possible.
Mass spectrometry
in combination with
gas chromatograw.0
phy (GC - MS) has
become established
as the analytical method of choice for this
application. The mass spectra obtained by
electron impact ionization in the full scan
mode yield detailed structural information which can be verified by comparing
with reference spectra. For this purpose,
in 1985 the authors of this work published
the first (two-volume) version, a compilation of over 1500 mass spectra of drugs,
poisons, and their metabolites. In this second. threc-volume edition the collection
has been enlarged to include data from
further toxicological studies. Of the 4370
spectra about 1500 are of drugs and poisons, 800 of pesticides and environmental
pollutants. and 2000 of metabolites.
In addition to giving mass spectra
(measured in their own laboratory) of all
these biologically active substances and
metabolites, with details of artefacts resulting from the sample preparation o r
from the gas chromatographic separation,
the authors also relate these directly to the
corresponding sample matrix (e.g., plasma, intestine contents, urine, or the pure
compound). Volume 1 describes the analytical procedures used, including extraction. derivatization, concentration, and
measurement of retention time (RT) index. Computer monitoring programs for
rapid detection of individual suspected
H I/
XI\^^,
rs~~u
mdn!lat#mli.&~xmm
d
Fir,
This section contains book re>iews and a list of
new books icceived by theeditor. Book reviews are
writtcn by invitation lrom the editor. Suggestions
for book:, to be reviewed and for book reviewers
are uelcome Publishers should send brochures or
(better) hooks to the Book Editor, Dr. Gerhard
Karger. Kediiktion Angewandte Chemie. Postfach
1011 61. D-69451 Weinheim. Federal Republic of
Gcrinsnq The editor reserves thc right of selecting
which hooks will be reviewed. Uninvited books
not chosen for revieu h i l l n o t be returned.
compounds are also given; with these one
searches for specific substances in defined
retention time windows using the ionspecific mass chromatogram. To complete
this volume there are tables in which the
substances are indexed according to compound name (or common name), active
groups, R T index, exact molar mass, and
CAS Registry number.
All this information, coded by means of
a set of abbreviations, as well as molecular
and structural formulas, is given along
with the individual mass spectra. One is
also told whether or not background subtraction has been applied to the spectrum
shown, since this can affect the intensity
ratios of the ions. Also important are the
indications given in cases where the analysis of standard solutions is essential for
unambiguous identification, and especially for quantification.
With electron impact ionization the
molecular ion peak, whose mass is the
most important piece of structural information. is not always strong enough to be
measured satisfactorily. Consequently the
arrangement of the mass spectra in Volu m e 2 (mi== 4 to 221 amu) and Volume 3 ( Y P Z ~ : = 222 to 777 amu) is not
wholly consistent, being in order of increasing mass of a characteristic fragment
ion or of the molecular ion itself. Thus, for
example, in the mass spectra of the morpholine fungicides one finds tridemorph
(p. 491) listed under the base peak mi: =
128, whereas fenpropimorph (p. 1502) appears under the molecular ion m / z = 303,
despite the fact that the base peak is at
m/: = 128. Consequently, when searching
for compounds according to their molar
mass one must first refer to Table 4 in Volume 1 to find the page numbers of the
corresponding spectra in Volumes 2 or 3.
In cases where there are two further ion
peaks with intensities greater than 80% of
the base peak, variations in measurement
conditions affecting the intensities can result in the mass spectrum appearing twice.
Thus. the metabolites of the neuroleptic
agent proinethazine-M (Nor-sulfoxide)
after acetylation give as the strongest ion
peaks 1y4i = 58 and rnji = 222 (base
peak). However, following the entry under m/== 58 (p. 104), the second entry
appears not under the base peak but under the molecular ion rnjz = 328 (p. 1634).
The system whereby an individual mass
spectrum can appear twice therefore
seems to be rather unhelpful, especially
since in this example only the mass spectrum on page 1634 is listed in the volume
containing the tables (Vol. 1).
The data systems of modern mass spectrometers include commercially available
libraries of spectra such as the NIST or
Wiley collections. containing as many as
130000 entries, which can be augmented
by users' own spectra libraries. One therefore has to question the justification for
producing this present spectra collection
in book form. However. a comparison of
the spectra entries reveals that the standard collections only partly cover the
range of compounds included in this
Pfleger/Maurer/Weber library. which is
expressly intended for use in systematic
clinical and toxicological analysis. and is
also an important resource for toxicological work in the fields of legal medicine, the
workplace, food analysis, and the environment, as well as the control of doping.
Whereas computerized spectra libraries
often consist only of reduced mass spectra, those reproduced in these volumes are
complete spectra with much useful additional information.
On-line library searching allows one to
apply different search criteria and thus offers greater flexibility, and therefore for
routine analysis it is desirable to be able to
use the Pfleger/Maurer/Weber library in
computerized form. However, it is not
available from all mass spectrometer
manufacturers, as licensing arrangements
d o not exist in all cases. Moreover, for
some mass spectrometers, especially older
ones, compatible data storage media are
not available, and thus the three-volume
work should prove a valuable resource in
these cases.
Robert Kveicig, Miifi'r Balicidir
Institut fur Okologische Chemie
und Abfdanalytik
der Technischen
Universitat Braunschweig ( F R G )
Relationshipsbetween Structure and Function of Cytochrome P-45O-Experiments,
Calculations, Models. (Series : Frontiers in
Biotransformation, Vol. 7.) Edited by K .
Ruckpaul and H . Rein. Akademie-Verlag,
Berlin, 1992. VIII, 370 pp., hardcover
D M 224.00. -ISBN 3-05-501 329-8
Researchers in the field of cytochrome
P-450 are currently investigating possible
ways around the unsolved problem of the
three-dimensional structure of the isoforms
of membrane-bound eukaryontic P-450.
Of the three prokaryontic soluble forms
of cytochroine P-450 that have so far been
crystallized. a detailed structural characterization has up to now been achieved for
only one of these (P-450-cam). Therefore,
in order to get the information about structure-function relationships that is so
essential for understanding the many
reactions of biosynthesis, toxicity. and
detoxification that are catalyzed by P-450.
there is no alternative to the approaches
based on modeling of proteins, directed
mutagenesis, matching of ligands, comparisons with analogous (or supposedly
analogous) model systems. more sophisticated methods of spectroscopic analysis,
etc. This volume collects together some of
the results obtained by such strategies.
The editors have recruited a team of
competent authors to prepare the ten
chapters. The book begins with a chapter
on that same P-450-cam (one is tempted
to add, in accordance with tradition). in
which Raag and Poulos emphasize the importance of matching the substrate to the
enzyme used for the catalysis. This is followed by a shorter contribution by Strobe1 summarizing current ideas about the
likely topology of eukaryontic cytochrome
P-450 variants in membranes of the endoplasmic reticulum. An excellent review by
Woggon and Matile provides an introduction to the ‘P-450 mimics’, metalloporphyrin models that can simulate the bonding to and activation of substrates, the
role of the thiolate group. and the embedding of cytochrome P-450 in lipid membranes. Lewis discusses, with an appropriate degree of reserve and critical caution,
the possibilities of using computer modeling as an aid to rationalization in making
predictions about carcinogenicity, in the
context of known metabolic reactions and
known structural characteristics of P-450
variants. In another highly informative
contribution Loew and Collins give an impressive account of the interesting results
(predictions of regio- and stereoselectivities) that can be obtained by integrating together a number of different experimental and modeling strategies. Hildebrandt contributes an article on studies of
P-450 by resonance Raman spectroscopy.
The articles that follow are concerned
with the characterization of enzyme systems, which one can expect to lead indirectly to further insights into the structure and
function of P-450. Hawkins and Dawson
discuss the only monooxygenase that is
not a P-450 (which catalyzes the oxidative
N-dealkylation of secondary amines in certain bacteria), mainly from the viewpoint
of the iron-oxygen interaction, while
Veitch and Williams give a general overview of electron transfer systems, including cytochromes c and b, and iron-sulfur
clusters. After this digression the two concluding chapter5 revert to concentrating
solely on P-450. G r a j summarizes current
knowledge regarding electron transfer in
P-450 monooxygenase systems, and discusses the importance of each individual
component, which involves some overlapping with the subject matter of the preced-
ing chapter. In the final article Lu gives a
lucid introduction to the interpretation of
the deuterium isotope effect and the contribution that this brings to understanding the P-450 catalyzed cleavage of C-H
bonds.
This book appears at a rather turbulent
time in the progress of such research. In
the first place, work is proceeding on the
three-dimensional structure of bacterial
P-450,,+,, which shows promise as a
model for most eukaryontic cytochrome
P-450 variants. but it has not been possible to include that work in this volume.
Secondly, there is active competition in
books on this theme: the past year saw the
appearance of Volume 206. Cjtochrorne
P-450. in the Mctlioils in Enzy?no/ogj series, which contains not only detailed procedures for the analysis of P-450 enzymic
activities. for purification, and for heterologous expression, but also some limited information about P-450 structures.
And now Volume 105 of the Handbook of
E.xperinien tal Phamiucology , also entitled
C:,.rochmnw P-4.50, has been published.
containing a greater number of individual
contributions which make up a survey
that is nearly exhaustive. although orientated mainly towards P-450 function.
In this area of research the volume reviewed here suffers from the disadvantage
that. although the chosen topics are certainly interesting and are competently reviewed (covering publications up to mid1991 in most cases), such a selection does
not provide a consistent overview of the
current state of knowledge on P-450 structural characteristics, nor is it claimed by
the editors to d o so. It seems to this reviewer that the work could have been improved if the editors had exercised firmer
control to impose some order: in particular it would have made life easier for the
reader seeking information if the contents
of the individual volumes of the series
were more clearly coordinated with each
other, at least by cross-referencing and
perhaps also by a cumulative index. For
example, important information relating
to the structure of P-450-cam (corresponding to Ch. 1 of this volume) also appears in Volume 4 of the series (Microhial
and Plant Cytochromes P-450), information on P-450 insertion into membranes
(corresponding to Ch. 2) also appears in
Volume 5 (Mernhrcine Orgmization and
Plzospliolipici Intrriiction of‘ Cjtocliromc.
P-450), and information on metalloporphyrin models (corresponding to Ch. 3)
can also be found in Volume 1 (Basis and
Meclianisnis of’ Regulation of’ Cytochrome
P-450).
Nevertheless, this volume forms an appropriate extension to and advance on the
earlier volumes that appeared in the Frontiers in Biotran.sforrnufion series from 1989
onwards. As a comprehensive work on this
field the series is almost unrivalled, and it
should be in the departmental library of
every laboratory with ambitions in this
area, whether concerned primarily with
biochemistry, microbiology, pharmacology. endocrinology, or protein structure.
W Nikolaus Kiilin- Velfen
Institut fur Physiologische Chemie
der UniversitCt Diisseldorf ( F R C )
A Dictionary of Concepts in NMR. (Biophysical Techniques Series. Series editor :
R . A . Dw.ek.) By S. W Homans. Clarendon Press, Oxford, 1992. VI, 372 pp.. paperback E 17.50.-ISBN 0-19-854765-X
This book is an introduction to the basic concepts of NMR spectroscopy. The
theoretical fundamentals are explained
under subject headings arranged alphabetically, together with a brief mathematical appendix on the properties of cartesian product operators, trigonometric
identities, matrix algebra. and rotation
operators. As the author explains in his
preface, the book is intended to help the
reader with a basic knowledge of NMR
spectroscopy to deal with the confusing
plethora of acronyms and technical jargon. He believes that this form of presentation enables the reader to get a quick
overview of a particular topic in N M R
spectroscopy without a laborious study of
the original literature. The book is intended especially for chemists and biochemists
concerned with applications, so that they
can remedy gaps in their understanding of
the methods that they are using to an ever
greater extent.
The subject headings have been well
chosen. There is a definite emphasis
on the description of multidimensional
N M R experiments on solutions, and
nearly all the applications described are
taken from the armory of methods used
for determining the structures of biochemical macromolecules. At least of
equal importance to this is the quality of
the information given. In this respect we
find that there are peaks and troughs.
Apart from a few small errors the most
important standard procedures such as
COSY and NOESY (each occupying
about ten pages) are explained clearly and
in considerable detail. with the help of the
product operator formalism. The liberal
use of the latter concept for describing
N M R experiments, combined with a good
introduction under the relevant subject
heading, is undoubtedly an important
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