Peptide hormones

TIBS - December I976

carbon dioxide and formaldehyde [7] were, Baly believed, capable of being converted by irradiation, and non-enzymatitally, into starch, according to the equations: CO,+H,O-+H,CHO+O, and, n H .CHO-+(CH,O),

He claimed to have photosynthesized formaldehyde from carbon dioxide and believed that the photosynthetic capacity of chlorophyll resided in its green colour. In demonstration of these ideas, carbon dioxide and water were irradiated in presence of a nickel oxide/thorium oxide catalyst. There was formed a compound, believed to be a form of starch, that was hydrolysed by takadiastase to reducing sugar [S]. References 1 Semmens, E. S. (1926) Nature 117,821-822 2 Baly, E. C. C. and Semmens, E. S. (1925) Proc. R. Sot. Ser. B97,25&253 3 Semmens, E.S. (1934) Nature 134,813 4 Semmens, E.C. (1932) Nature 130,243 5 Semmens, E. S. (1948) Biochem. J. 43, xviii 6 Semmens, E.C. (1949) Nature 163,371 7 Peat, S., Bourne, E.J. and Whelan, W.J. (1948) Nature 161,762 8 Baly, E.C. C. (1939) Proc. R. Sot. Ser. A172, 445465 W. J. WHELAN W. J. Whelan is Professor of Biochemistry at the University of Miami, Miami, Florida, U.S.A.

293

Righetti and Drysdale in their excellent survey of IEF in Part 2 of this volume do not accept the inevitability of this situation. Not only do they describe a method by which the number of ampholytes used in a particular experiment can be ascertained but also they give details of how mixtures similar to the commercial Ampholine can be synthesised. Unfortunately, the products thus obtainable are coloured and difficult to decolourise. However, as Righetti and Drysdale point out, many of these coloured substances are themselves amphoteric and thus able to contribute1 towards formation of pH gradients. A further, well-known disadvantage of commercial Ampholines, which surprisingly is not mentioned in this book, is that mixtures which are advertised as being able to give pH gradients between certain values in fact yield somewhat shorter ranges. / The above facts, together with the very high prices of reagents which are rather simple to prepare, inevitably lead to adverse criticism of the manufacturers by most users of Ampholine. Fortunately, the appearance of informative books like this must help towards a needed rectitication, and Righetti and Drysdale make the useful suggestion that less pure Ampholine might be sold at a lower price. This should be quite adequate for large scale, preparative experiments. Apart from certain minor criticisms this book can be recommended to all those using IEF. Perhaps most important is the confusion likely to be caused by the duplication of ‘d(pH)/’ in Eqn 18 and the omission of an oblique line between ‘d(pH)’ and ‘dx’ in the numerator of Eqn 19 on p. 354. Finally, the explanation concerning the importance of minimum volume for the electrode vessels used when IEF is conducted in gel rods is hardly convincing. Why should ‘convective mixing’ have such adverse effects?

may be mentioned. Also, this Table is referred to on p. 82 as Table 14.1. Some further cross-referencing would be desirable. Thus N.C.S. is mentioned on p. 54 (with a reference). ‘NCS’ appears on the next page. Evidently a cross reference to page 97 would have been helpful as on that page the significance of these initials as ‘Nuclear Chicago Solubilizer’ is revealed. The last 20 pages of the book are devoted to five appendices, all of which are useful. Appendix 3 is especially so because HUGH GORDON it provides a primary guide to the most H. Gordon is a member of the scientific staff of the appropriate method of counting for par- National Institute for Medical Research, Mill Hill, London, U.K. ticular samples. This book includes much more than is suggested by its title but as has already been indicated it covers in reasonable detail a wide field, some knowledge of which is required to determine optimum Chemistry and Biochemistry of conditions for estimation of radioactivity Thiocyanic Acid and its by liquid scintillation counting. Isoelectric focusing (IEF) has higher Derivatives edited by A.A. Newman, published by resolving power than any other method Academic Press, London, New York, San used for separation of proteins. UnfortuFrancisco, 1975. E12.- (approx $24.-) nately to achieve such separations (xiv+351 pages) ‘Ampholine’ or other commercially availOne would not have believed it possible able mixtures of amphoteric substances are required, and the manufacturers are 1that a book solely concerned with the not prepared to supply complete analytical ! chemistry and biochemistry of thiocyanates could possibly be interesting. Useful, data.

All facets of thiocyanates revealed

perhaps, but hardly the topic to elicit enthusiasm. In this book every conceivable facet of the subject is revealed and though opinions may differ on its importance, the authors have certainly striven to highlight the more appealing aspects. I enjoyed particularly the chapter on ‘General Chemistry’ by M. N. Hughes; that on ‘Coordination Chemistry’ by J. L. Burmeister dwelt overlong on certain pseudo-theoretical aspects for my taste. I remain unconvinced about the possibilities of ‘Molten Thiocyanates’ as described by D. H. Kerridge but found the chapter on ‘Biochemistry’ by J. L. Wood absolutely fascinating, especially as it drew attention to so many unsolved problems concerned with the formation, metabolism and physiological chemistry of thiocyanate. H. A. Beekhuis describes the ‘Technology and Industrial Applications’ in a wellbalanced manner. The ‘Analytical Chemistry’ is thoroughly covered and, though it could not be described as light reading, is a competently constructed account. The book will probably find its way on to few shelves. However, it is a valuable addition to the literature and the chapters by Hughes and Wood should repay closer study. H. A. 0. HILL ,H. A. 0. Hill is Lecturer in Organic Chemistry at the Universiiy of Oxford, Oxford, U.K.

Beginner’s text Peptide

hormone

Hormones

edited by J. A. Parsons, published by (Macmillan) The British Council, London, 1976. E15.- (approx. $30.T) (399 pages)

Polypeptide hormones are the concern of biochemists, immunologists, clinicians, physiologists, pharmacologists and many others, and so hormones have a varied physiognomy. To some they are a chemical structure, to others an immunoreactivity, or even a set of initials - V.I.P., HPL, ACTH and so on - on a vial provided by a generous ‘synthetic’ chemist or biochemist. This complexity of interests makes the presentation of data in the form of an introductory text a real challenge, but it is one that is met bravely by the editor of and contributors to this very readable and useful book. Peptide Hormones includes some excellent reviews on insulin and glucagon, gastromtestinal hormones, parathyroid hormone and calcitonin, neurohypophysial hormones, the renin-angiotensin system, pituitary hormones, human chorionic gonadotropin and hypothalamic hypo-physiotropic hor-

TIBS - December I976

294 mones. We are told in Chapter 3 that we need not define too closely the term peptide hormone : ‘it is used in this contribution to mean a polypeptide of known constitution, with a molecular weight of less than 10,000 daltons which has, or may be presumed to have hormonal activity.’ However, four other chapters concern the growth hormone family and the two subunit glycoprotein hormones which have molecular weights in excess of 20,000. ‘Polypeptide hormones’ may have been a more appropriate title. The text, which derives from a meeting sponsored by the Biological Council in 1974, is divided into three sections. The first of these concerns general aspects of the hormones. It begins with a concise summary of the chemistry by J. Rudinger, one of the most outstanding peptide chemists working in this area, whose death sadly occurred last year. However, the discussion in the subsequent chapter of the conformation of hormones represents the most unsatisfactory part of the book. We are treated to diagrams of the cc-helix and /?-sheet - hardly an imaginative contribution - followed by several pages of discussion and methods of conformation prediction which can only be noted for their unreliability. However, there is no mention of the precise determination of the structure of insulin nor of the nuclear magnetic resonance studies of small peptides like oxytocin which must surely be more useful in defining conformations important for receptor binding. Other introductory sections concern the evolution of polypeptide hormones, both in terms of sequence homologies (H.D. Niall) and (A. G. relationships developmental Pearse). A review by D. F. Steiner of hormone precursors contains an interesting discussion of some possible functions of precursors. This is a complicated area; precursors may play many roles including regulation of the secretory product, and precise adjustment of the hormone in terms of not only receptor binding properties but also metabolism, degradation and vascular permeability. Alternatively, the larger sequences may be related to the constraints of transcriptional or translational unit size or to their evolution reflecting their origin from pre-existing gene products. In another chaper J.T. Potts discusses preproparathyroid hormone ; the more recent of other pre-prohormones discovery makes this a general phenomenon which may be related to sequestration of the hormone by the endoplasmic reticulum, immediately after or during synthesis. Endocrine pharmacology is also dealt with in a very useful and well written contribution by J. A. Parsons. The assumption

that hormones do not cause side effects is challenged and the discussion shows that overall patterns of response in vivo vary qualitatively not only with dose but also with the rate and site at which the hormone enters the circulation. This is clearly important in the clinical use of these hormone preparations. The second section comprises reviews of individual hormones. Almost all are contributed by distinguished innovators in their fields of research, G. F. Cahill, M. I. Grossman, R. E. Canfield, R. Guillemin, G. E. Bisset, to name a few. They are concisely written and in general cover the whole range of biochemical and physiological aspects of the hormone, at the same time emphasising recent some important results. In particular, W. S. Peart’s discussion of the renin-angiotensin system is very well presented and its interest is even further heightened by the results, in the last year, on the relation of the enkaphalins to fl-lipotropin which probably involves an enzyme system similar to renin. The final section reviews the biochemical mechanisms of hormone action. Although there are interesting contributions on ACTH-receptor interactions by Schwyzer and Schulster’s groups, the book fails to reflect the great excitement and interest in this area during the last seven years which has qualitatively changed our understanding of hormone action. There is, however, a very useful discussion by P. Cohen which highlights the problems of finding the intracellular sites of action of those hormones like insulin where the nature, and even the existence, of a second messenger is the subject of continued debate. This is a very useful text which is probably the best starting point for students interested in learning about polypeptide hormones in general. It is also one to which I will often make reference. It should be an important part of the library of any research group working with polypeptide hormones. TOM BLUNDELL

T. Blurtdeli is Professor of Crystallography of Molecular Biology and Director of a research group concerned with the structure andbiology ofpolypeptide hormones, at Birkbeck College, University of London, London, U.K.

Helpful

to specialists

Ageing, Carcinogenesis and Radiation Biology, the Role of Nucleic Acid Addition Reactions edited by K. C. Smith, published by Plenum Press, New York and London, 1976. $47.40 (approx &25.-) (xi+561 pages)

The association between, or a unifying theme to link, the three subjects in the title of this book will by no means be immediately obvious to the majority of potential readers. It is therefore very much to the credit of K. C. Smith and the many contributors to this volume that they have kept this objective to the fore in their presentations and have made a strong case for considering that research activities in these three fields have much in common. More specifically the intention has been to delineate a role for nucleic acid addition reactions, and particularly those involving nucleic acids and proteins, in these various areas of research. I shall not attempt to comment on individual chapters or contributions, which would probably only reflect personal interests and prejudices, but rather I shall attempt to give an indication of the broad areas covered by the twenty-four separate articles. Thus there are articles on four main areas of research which relate to the topic of nucleic acid adducts. The first is concerned with such aspects as the contentious role of protein linkers in DNA in determining the architecture of the eukaryotic chromosomal DNA, and how DNA is attached to membranes, and the involvement of membranes in DNA replication and chromosomal segration. The basis for the specificity of such reactions as the interaction of a repressor with its operator DNA, of DNA polymerase with DNA, of ribosomal protein .with RNA, of aminoacyl transfer RNA synthetase with transfer RNAs are important current questions which involve DNA-protein interactions. The selective control of localised DNA strand separation to permit RNA synthesis during transcription and the onset of DNA synthesis during gene replication are no doubt mediated by a variety of associated chromatin molecules, and these processes are presumably vitally involved in the mechanisms of both ageing and carcinogenesis. The inclusion of some recent concepts on the structure of chromatin and its role in these processes would therefore have added to the completeness of the volume. It is relevant that cross-linking techniques evolved in radiation biology have now been used to investigate packing arrangement of the DNA in phage, the association of sites between specific ami-