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Transcript
796
BIOCHEMICAL SOCIETY TRANSACTIONS
and the articles are generally of a high standard. Most of the authors review data from
studies on normal and abnormal women, but, where clinical information and/or the
results of studies made in vitro are not available, animal models are used.
The first chapter is concerned with the histology and development of the human
ovary, and the second deals with the interrelationship of cyclic AMP, steroids and
prostaglandins during the ovulatory cycle of the rabbit. Subsequent chapters deal with
the steroidogenic capacity of ovarian cells, the role of prostaglandins in gonadotropin
secretion, metabolism of the oocyte during growth and maturation, regulation of blood
flow, the release of follitropin and lutropin, and steroid secretion. Other articles are
concerned with abnormalities of reproduction (amenorrhoea, hypogonadism, polycystic
ovaries, pituitary tumours, anorexia nervosa etc.) and on the role of prolactin in ovarian
function. The book concludes with chapters on such diverse topics as the biochemistry
of ovarian cancer, ‘virilizing’ luteoma, hirsutism, and androgen secretion and
metabolism.
The order in which the various chapters appear in the book is rather arbitrary and
probably follows that in which the papers were presented during the symposium rather
than a logical sequence. Thus the chapter on hypothalamic-hypophysial-gonadal
feedback, which might be expected to appear at the beginning of the book after the
chapter on histology, is actually the ninth chapter. It is also difficult to see the logic of
putting together chapters on specific binding of gonadotropins, puberty, the postmenopausal period and amenorrhoea.
In spite of the rather peculiar order of the articles and a few minor inconsistencies
in terminology, this book will be of great value to biochemists and physiologists in
providing comprehensive information that otherwise would be difficult to find in a
single volume.
T. G. BAKER
Function and Metabolism of Phospholipids in the Central
and Peripheral Nervous System
G.PORCELLAT1, L. AMADUCCI and C. GALL1 (Editors)
Plenum Press, New York, 1976, pp. 412, $4.5.00
This book reports on the International Satellite Meeting on ‘Phospholipids in the
Nervous System’ held at Cortona, Tuscany, Italy, in August 1975. Its prompt publication
in 1976by Plenum Press is therefore of great service to lipidologists and neurochemists.
The book is well edited, although I would argue with the allocation of some of the papers
to the various sections. I could only spot one major editorial error (a graph wrongly
placed on page 190).
It is widely accepted now that the phospholipid bilayer offers the cell its basic
permeability barrier and ascribes to biological membranes its own elastic and dynamic
properties. The physical chemist featured prominantly in establishing this aspect of
phospholipid function in biomembranes. This conference reports mostly on the other
side of the coin, i.e. the contribution of biochemistry to understanding the functional
significance of phospholipid metabolism in membranes. In this review, I shall discuss
only some of the papers reported, mainly to encourage the reading of others.
The most exciting phenomenon discovered in this field in recent years is the
response of phosphatidic acid and phosphatidylinositol metabolism to extracellular
stimuli. Michell et al. summarized some of these observations, and integrated them
into a working model for the possible role of phospholipids in membrane fusion.
This model depends on the production of diacylglycerols as an essential step in
the turnover of these two phospholipids. This happens on one or the other of the
membrane surfaces, and the induced changes in the packing of membrane components lead to vesicle budding either in or out of the cell. We now know that,
1977
BOOK REVIEWS
797
owing to thermodynamic considerations, phospholipids can flip-flop only very slowly
from one side of the membrane to the other. Would the diacylglycerol molecules be
similarly restricted, and remain long enough in one-half of the bilayer to create these
vesicle buddings? Moreover, are the enzymes involved so asymmetrically distributed
as to catalyse these directional buddings? This is certainly an area of research in which
much progress is expected.
Other papers describe some recent results on the mechanism of this phenomenon.
Hauser & Eichbergdifferentiatebetween the enzymic sites of action of neurotransmitters
and cationic amphiphilic drugs (e.g. DL-propanolol). The former are now thought to increase the rate of phosphatidylinositol degradation, and the latter to decrease the rate of
phosphatidic acid breakdown. Hawthorne et al. suggest that these differences may
be correlated with post-synaptic and pre-synaptic events respectively. The former
may involve the integrated turnover of phosphatidic acid and phosphatidylinositol,
and the latter only the independent turnover of phosphatidic acid.
Yet another dimension is added to the role of phospholipids in the nervous
tissue from studies on the effect of brain damage on their metabolism. Ischaemia and
other treatments such as electric shock cause a rise in the free fatty acid concentrations
of brain. It is mostly represented by arachidonic acid, and again phosphatidylinositol
is implicated as the source. The production of arachidonicacid is enzymic in nature and
may be influenced by cyclic nucleotides.
A fascinating topic touched upon in the conference is the turnover and maintenance
of myelin phospholipids. Horrocks et al. describe a method for the correct calculation
of the proportions of fast- and slow-turning-over pools of phospholipids. Application
of the method to myelin and microsomal fractions from brain indicate that both
membranes contain ‘fast’ and ‘slow’ pools with half-lives that are not greatly different.
The myelin fraction, though, contains much less of the ‘fast’ pool than the microsomal.
Presumably the ‘fast’ pools are those that undergo phospholipid exchange, and in the
adult animal are in dynamic equilibrium with the phospholipids of other membranes.
If myelin, then, derives only a small proportion of its phospholipids by exchange, how
are they maintained in the adult animal or deposited in the first place in the immature?
Some of the answer comes from an exciting and careful paper by Dawson & Gould.
They used radioautographyto demonstratethat freshly acquired phospholipid molecules
migrate slowly from the outer to the inner lamellae of myelin by lateral diffusion.
I approached the section on the pharmacological action of phospholipids with
some suspicion, and, I must admit, after reading it my feelings did not alter much.
The principle is simple. One talks of the action of a drug if it is unaltered before reaching
its target, or at most if it is altered into a well-defined form. To say the least, crude
lipid extracts of tissues are not a single molecular species,and the abundance and variety
of enzymes that change them in the organism makes one uncertain of the final form or
of the exact site of pharmacological action. It is not even good enough in this context
to use purified egg lecithin. Moreover, not one paper stated a check on the autoxidation
of the samples used. The most one could justifiably say from the results of this section
is that some phospholipids do manage to arrive at the brain on intravenous administration. This is not new, but we are further told that phosphatidylserine has a specific
effect on brain acetylcholine and brain glucose concentrations in a dose-dependent
manner! Perhaps the authors realize this difficulty of interpretation, since much of the
discussion in this section is speculative.
Of course, there are many papers I have not discussed in this review. It is fair to say,
however, that, inasmuch as this book describes the effects of extracellular stimuli, it also
abounds with stimuli for research thought, and thus deserves much contemplative
reading.
A. SHELTAWY
VOl. 5