2002 by The International Union of Biochemistry and Molecular Biology Printed in U.S.A.

BIOCHEMISTRY

AND

MOLECULAR BIOLOGY EDUCATION Vol. 30, No. 4, pp. 221223, 2002

Metabolic Minimap Metabolic Minimaps of Glycolysis and Gluconeogenesis and Their Regulation, Designed by Donald E. Nicholson
COMMENTARY: METABOLIC MINIMAPS ARE USEFUL TOOLS
Received for publication, May 3, 2002 Richard W. Hanson From the Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4935

This issue of Biochemistry and Molecular Biology Education (BAMBED) presents metabolic minimaps by Dr. Donald Nicholson on the reactions and control of gluconeogenesis and glycolysis (Figs. 1 and 2). These are the fourth and fifth in a series of metabolic minimaps to be published in these pages [13]; when completed, they will cover all of the major pathways of intermediary metabolism. As any student of biochemistry can readily attest, metabolism can be a very intimidating subject. It often seems to be all details and very little theory. This is complicated by the complexity of the interaction between the specific metabolic pathways. A student may memorize a give metabolic sequence only to find that it interacts with another pathway that is critical to the regulation of yet a third set of reactions. As Sir Hans Krebs once said, when asked why the control of the citric acid cycle seems overly complicated, complexity is the starting point. And so it is! Without some aids to help keep it all straight, it would be very easy to lose the forest for the trees. Donald Nicholsons metabolic minimaps will provide the student of biochemistry with a valuable tool for keeping the facts straight. The first minimap shown here presents the major reactions in glycolysis and gluconeogenesis, complete with International Union of Biochemistry and Molecular Biology enzyme numbers and the names of the enzymes to match their numbers listed below. There are no structural formulas presented; it is assumed that the student has a working knowledge of the various structures or can look them up in a textbook if required. This greatly simplifies the map and makes it easier to follow. A critical perusal of the map provides a wealth of information for the initiated. For example, the minimap clearly indicates the cellular compartmentation of gluconeogenesis in the mitochondria and cytosol (the reader is left on his/her own to know that 3.1.3.9, glucose-6-phosphatase, is in the endoplasmic reticulum). All of the reactions of glycolysis are located in the cytosol. The key role of the citric acid cycle in generating the carbon used for gluconeogenesis (anaplerosis and cataplerosis), as well as the reducing power (NADH) and the ATP required for this
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process, is indicated clearly. One can even find the directionality of efflux from the mitochondria to the cytosol of the various citric acid cycle anions involved in glucose synthesis presented in the minimap. The important metabolic roles for gluconeogenesis in liver and glycolysis in muscle are indicated, as is the interconnection between the tissues via the Cori cycle. Even the effect of the fed and fasted states on hepatic glycolysis and gluconeogenesis is presented. Its all there and in a most accessible format. How should one use the metabolic minimaps? The answer will vary between teacher and student. Both should welcome having the metabolic pathways laid out so clearly. For students, the maps can be readily downloaded from the BAMBED web site [4] and used to annotate lectures. As the details of the regulation of these metabolic pathways accumulate, the major regulatory points in each pathway can be noted, and the rate-controlling enzymes can be underlined. For example, the negative feedback regulation by citrate on phosphofructokinase could be noted as could the reciprocal control of this reaction by ATP and AMP. For teachers, the availability of a concise set of reactions that are easy for students to follow should provide a adjunct to available text books of biochemistry. I can imagine the metabolic minimaps acting much as a road map by providing a guide to the location of specific facts in a variable landscape of reactions. It is important to stress that the metabolic minimap is a work in progress. Donald Nicholson (donald.nicholson@ which.net) and the Editors of BAMBED welcome your feedback on how the minimaps can be improved so that they are even more useful. With your help, errors can be corrected and additions made. For example, a regulatory minimap that contains all of the control points in the pathways of gluconeogenesis and glycolysis is also included here and might be used as an overlay to provide an integration of concepts for both the reactions of a metabolic pathway and its regulation. Dr. Nicholson is to be complimented for his dedication to this project and for the wonderful outcome. However, no tool is of value unless it is used; your feedback on the usefulness of these metabolic minimaps is thus important for their ultimate success.

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FIG. 1.

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FIG. 2.
REFERENCES
[1] D. E. Nicholson (2001) IUBMB-Nicholson metabolic pathways charts, Biochem. Mol. Biol. Educ. 29, 42 44. [2] D. E. Nicholson (2001) Pentose phosphate pathway(s) minimaps, Biochem. Mol. Biol. Educ. 29, 179 182. [3] D. Nicholson (2002) Mitochondrial ATP formation, Biochem. Mol. Biol. Educ. 30, 35. [4] http://www.bambed.org.