16 October 2007 © 2007 The Biochemical Society

Features

Biochemistry textbooks: are they getting better?

When I was a young lecturer at Birmingham in the 1970s each student had to write a review of a book chosen from a list of four or five possibilities during the summer vacation after completing the second year of biochemistry. At least half of them chose to write about the same book, always saying how clear and understandable it was. After 2 or 3 years of reading these essays I decided that I ought to read it myself, and found it to fall far short of what I expected. Still available more than 30 years later, it is not the worst book on biochemistry ever written, but it is cheap and short, and has sold many thousands of copies. I started asking students who had reviewed it favourably to check some factual information with me. It would have been too easy to choose a topic that I know well, such as enzyme kinetics, or one that everyone finds difficult, such as thermodynamics; however, I usually chose to look at the stereochemistry of simple sugars, a subject where I have no more knowledge than every teacher of biochemistry can be expected to have. With a little coaxing (or in some cases a lot) they were then able to find the mistakes in the use of the Fischer convention, in the meanings of the stereo‑ chemical prefixes and their relationship (or lack of one) to the polarization of light, and so on, and I told them to re‑read the whole book in a proper critical spirit.

to present kinetics intelligibly. Even such a simple mat-ter as drawing a reasonably accurate curve representing the Michaelis–Menten dependence of rate on substrate concentration was once beyond the capacity of virtually all textbook authors, and although this has improved in 35 years there is still some way to go. Grossly inaccurate curves in which the limiting rate is reached at about 5Km can still be found, and some authors who draw the curve adequately on one page show it badly on another. I find it hard to know how one can explain to students that one cannot estimate the parameters accurately from a plot of rate against substrate concentration if one assigns them a textbook that indicates plainly that one can!

Maybe I should move away from my personal in-terests to discuss other aspects of biochemistry, such as the structure of proteins. I long had a belief that most textbook authors did not believe in the reality of zwit-terions. Even Mahler and Cordes1 followed what was then the standard pattern in describing amino acids, first mentioning (p. 9) the fictitious ‘neutral’ structure NH2–CHR–COOH, and presenting the structures of all the important amino acids in terms of it. They then added a ritual mention of the real structure (p. 15), but made it clear that they didn’t believe a word of it by reverting to wrong structures for the rest of the book. In my early years at Birmingham I sometimes complained about this to senior colleagues, who typically said that it was not important because students knew when they saw NH2–CHR–COOH that it meant NH3

+–CHR–COO– and any-way, knowing that amino acids were zwitterions was not

This experience encouraged an already lively interest in the accuracy of the information supplied by general biochemistry textbooks, and I was not happy with what I found. Of course, it must be obvious to everyone that even by 1970 biochemistry had become such a huge sub-ject that no one could be expert in all of it, and it was a brave author who could even contemplate the idea of writing a book of more than 1000 pages that was sup-posed to cover the whole field. Even when expert review-ers check each section of a book there are bound to be a few mistakes that escape detection until after it is too late to correct them. Nonetheless, there remain some errors that are quite elementary and yet continue to be copied from book to book.

The first general textbook of biochemistry that I bought was the 1st edition of Biological Chemistry by Mahler and Cordes1, which had been published in 1966; it has also proved to be the last widely known general text-book to make a serious effort to describe the kinetic be-haviour of enzymes. All of its well known successors have treated the subject as one that was essentially completed by Lineweaver and Burk in 1934. In a sense, therefore, one can claim that the dumbing down of biochemistry to meet the capacities of the weakest students has been going on for a long time, but that is not really fair, because the books that preceded Mahler and Cordes were no bet-ter in this respect than the ones that succeeded them. The truth is rather that most authors of textbooks, even in the 1960s when the study of enzymes was regarded as the core of biochemistry, have found it too difficult

Athel Cornish-Bowden (Unité de Bioénergétique

et Ingénierie des Protéines,

Marseille, France)

Key words: education,

errors, inaccuracy, textbooks

Of the making of books

17October 2007 © 2007 The Biochemical Society

FeaturesWhat is biochemistry?

necessary for understanding their properties. I thought that the first half was wishful thinking, and the second half gro-tesquely wrong. How can students who think that glycine combines the attributes of acetic acid and ethylamine fail to be surprised to learn that it is a white and odourless crystalline solid, and not a strongly smelling liquid or gas? How can they understand why it is a far weaker acid than acetic acid, and a far weaker base than ethylamine? It looks, smells and behaves like a salt because it is a salt; no more recondite ex-planation is needed. What one cannot guess from a knowledge of the structure (though a classically educated person might guess it from the name) is that glycine tastes like sugar, but now we are into physiology rather than chemistry.

I take Mahler and Cordes1 as an example not because their book was the worst of its time, but because it was about the best. The really bad books available in 1970 did not mention zwitterions at all. In this respect, at least, general textbooks have im-proved enormously in the past 35 years, and I know of no current textbook that follows the full pat-tern that I have described. Most modern books get the structures of amino acids more or less right, though some misconcep-tions continue to be encour-aged, such as the idea that the ionization is a consequence of being dissolved in water.

People who think that enzyme kinetics is too difficult to be taught properly may also think that ionization is too advanced to be considered important, so let us turn to a different example. The structure of glycogen was established by William Whelan’s group2 in the early 1970s. It is a very large spherical molecule, consisting mainly of polymerized glucose but with a small protein, glycogenin, at the centre. This protein is at-tached to a single C chain, which branches out into equal numbers

Of the making of books

18 October 2007 © 2007 The Biochemical Society

Features What is biochemistry?

of A and B chains, all of these being essentially equal in length and with two branch points in each B chain. This structure is easy to describe, easy to remember, and easy to draw, at least for the first few layers. Why then, do textbooks insist on representing an obsolete view of the structure that dates from 1940, that is more irregular and much more difficult to remember and draw? (Note, inci-dentally, that there is no controversy about this: no one who has studied the structure of glycogen thinks that the earlier structure is correct.) When I surveyed all of the major general textbooks of biochemistry a few years ago there was not a single one (out of ten examined) that gave the correct structure: two gave no structure at all for the whole molecule, one (the 5th edition of Berg, Tymoczko and Stryer’s Biochemistry3, but unimproved in the current edition4) showed it in such a vague way that it was difficult to discern what it was supposed to represent (though it was probably the obsolete struc-ture), and the other seven showed the obsolete structure. In several cases glycogenin was not mentioned, and when it was it was mentioned out of context or given a fantastic function: Berg and co-workers3,4 claim that the size of glycogen granules is limited by the interaction between glycogen synthase and glycogenin, but they do not explain how an enzyme acting on the surface of a huge molecule can interact with a small protein buried in its centre.

The liver isoenzyme of hexokinase has been re-garded as worthy of a brief mention in textbooks since it was discovered, but it remains the subject of many mis-conceptions. For example, the following sentence from Garrett and Grisham’s Biochemistry5 makes three points, all of them wrong: ‘Liver contains an enzyme called glucokinase, which also carries out the [hexokinase] reaction, but is highly specific for d-glucose, has a much higher Km for glucose (approximately 10.0 mM), and is not product-inhibited.’ In reality the liver isoenzyme is no more specific for glucose than the other isoenzymes found in mammals, and the authors have been misled into thinking that the popular (but ineradicable) misno-mer ‘glucokinase’ for it provides a guide to its specificity. As it does not follow Michaelis–Menten kinetics it has no Km, and although it is true that inhibition by glucose 6-phosphate is too weak to be physiologically significant it is not true to say that it is not product-inhibited. These

mistakes have appeared in many textbooks, but, unlike some that I have mentioned, they are becoming less fre-quent, perhaps as a result of the new prominence for the enzyme that has come with recognition of its implication in maturity-onset diabetes of the young.

In this short article I have refrained from discuss-ing aspects of biochemistry that I have only a superficial knowledge of, such as the notion that plants do not con-tain cholesterol, and ones that I know quite a lot about but which will be regarded as esoteric by many readers, such as metabolic control analysis. Even within mainstream biochemistry, however, there are numerous beliefs that have been known to be wrong for many years and yet continue to be repeated in textbooks. Does it matter, and if so what can be done about it? In some cases it clearly does matter: anyone designing a low-cholesterol diet needs to know that plants contain cholesterol in amounts that may be small but are by no means negligible. One might be tempted to expect multi-author textbooks to contain fewer errors than single-author textbooks, and in either case a large panel of expert reviewers should eliminate them. Unfortunately the example of Zubay’s Biochemistry6, which has eight other contributing au-thors (and acknowledges 20 contributors to previous editions) and benefitted from the advice of many other experts, does not really bear out this hope, as it is not no-ticeably more accurate than competing books. Moreover, a multi-author book can hardly avoid suffering from an unevenness of style and treatment. Probably the number of authors of any textbook needs to be kept small, but they need not only to seek criticism from qualified ex-perts but also to follow the advice they receive. ■I am most grateful to Christopher Lai (Imperial College, London) for checking the factual information in this article.

References1. Mahler, H.R. and Cordes, E.H. (1966) Biological Chemistry, 1st edition,

Harper and Row, Tokyo2. Gunja‑Smith, Z., Marshall, J.J., Mercier, C., Smith, E.E. and Whelan, W.J.

(1971) FEBS Lett. 12, 101–1043. Berg, J.M, Tymoczko, J.L. and Stryer, L. (2002) Biochemistry, 5th edition,

W.H. Freeman, Reading

4. Berg, J.M, Tymoczko, J.L. and Stryer, L. (2007) Biochemistry, 6th edition, W.H. Freeman, Reading

5. Garrett, R.H. and Grisham, C.M. (2005) Biochemistry, 3rd edition, Thomson Brooks/Cole, London

6. Zubay, G. (1998) Biochemistry, 4th edition, McGraw–Hill, New York

Athel Cornish-Bowden is Directeur de Recherche in the CNRS unit of bioenergetics and protein engineering, Marseilles, France. He is interested in the kinetics of enzyme-catalysed reactions, especially in multi-enzyme systems, and in

metabolic regulation. In addition, he has long been interested in the accuracy of the information to be found in general textbooks of biochemistry. email: acornish@ibsm.cnrs-mrs.fr