© 2002 by The International Union of Biochemistry and Molecular Biology
Printed in U.S.A.
BIOCHEMISTRY
MOLECULAR BIOLOGY EDUCATION
Vol. 30, No. 4, pp. 221–223, 2002
AND
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 [1–3]; 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 Nicholson’s 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
‡ To whom correspondence should be addressed. Tel.: 216368-5302; Fax: 216-368-4544; E-mail: rwh@po.cwru.edu.
This paper is available on line at http://www.bambed.org
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. It’s 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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BAMBED, Vol. 30, No. 4, pp. 221–223, 2002
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, Bio-
chem. Mol. Biol. Educ. 29, 179 –182.
[3] D. Nicholson (2002) Mitochondrial ATP formation, Biochem. Mol. Biol.
Educ. 30, 3–5.
[4] http://www.bambed.org.