© 2006 by The International Union of Biochemistry and Molecular Biology BIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION

Printed in U.S.A. Vol. 34, No. 4, pp. 275–277, 2006

Articles

Pentose Phosphate and Calvin Cycles

SIMILARITIES AND THREE-DIMENSIONAL VIEWS*

Received for publication, December 6, 2005, and in revised form, February 8, 2006

Antonio Sillero‡§, Vitali A. Selivanov¶, and Marta Cascante¶

‡From Departamento de Bioquı́mica, Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de
Investigaciones Cientı́ficas-Universidad Autónoma de Madrid, Facultad de Medicina, Universidad Autónoma de
Madrid, Arzobispo Morcillo 4, 28029 Madrid, Spain and the ¶Departamento de Bioquı́mica i Biologia Molecular,
Facultat de Quı́mica and Centre de Recerca en Quı́mica Teòrica at Parc Cientific de Barcelona,
Catalunya, Spain

The main object of this work is to present simplified and three-dimensional views of the pentose phosphate
and Calvin cycles, emphasizing their functional and chemical similarities.
Keywords: Pentose phosphate cycle, Calvin cycle, tri-dimensional representation.

The pentose phosphate and Calvin cycles are usually
illustrated, in textbooks [1– 8] and other publications
[9 –14], as bi-dimensional diagrams composed of nodes
and lines (representing substrates and enzymes) and with
connections with the glycolytic pathway. Both cycles
share characteristics that make them different from other
classical linear pathways. Some of their substrates: (i)
participate in bi-substrate reactions, (ii) are the center of
small metabolic crossroads as can be metabolized by 2–3
enzymes, and (iii) are part of cyclic pathways. Thus, the
planar representation of both cycles is usually composed
of intercrossing lines that cannot be easily grasped by
students of biochemical courses. Also, the similarity be-
tween both cycles is not clearly visualized. As shown be-
low, these difficulties have been partially solved by a three-
dimensional representation of the pentose phosphate (Fig.
1) and the Calvin pathways (Fig. 2). For additional details,
the student may consult any of the excellent biochemistry
textbooks presently available.
PENTOSE PHOSPHATE CYCLE (FIG. 1)
This cycle is a major cytosolic pathway of carbohydrate
metabolism in some tissues, an alternative to glycolysis for
the oxidation of glucose in all tissues, and essential for the
synthesis of NADPH (a dinucleotide required mainly, but
not exclusively, for biosynthetic pathways) and ribose-5-
phosphate (a precursor of purine and pyrimidine nucleo-
tides). Two stages are usually considered in this cycle: the
oxidative and non-oxidative phases of the pentose pathway.
In the oxidative part (Fig. 1), glucose-6-phosphate is trans-
* This work was supported by grants from the Instituto de Salud
Carlos III (Grant RMN-C03/08) Madrid, Spain (to A. S.); the Span-
ish Ministerio de Ciencia y Tecnologı́a (Grants SAF2002-02785
and PPQ2003-06602-C04) (to M. C.), and Generalitat de Catalu-
nya (Grant ABM/acs/PIV2002-32) (to V. A. S.).
§ To whom correspondence should be addressed. E-mail:
antonio.sillero@uam.es
This paper is available on line at http://www.bambed.org
formed into ribulose-5-phosphate by the action in sequence
of three enzymes (numbered as in Fig. 1): glucose-6-phos-
phate dehydrogenase (1), gluconolactonase (2), and 6-fos-
fogluconate dehydrogenase (3). During this part, formation
of 1 mol of CO2 and 2 mol each of NADPH and proton takes
place per mole of glucose-6-phosphate (Fig. 1; Table I).
The interchange of carbon atoms between the glycolytic
and the pentose pathways takes place at the level of
fructose-6-phosphate and/or glyceraldehyde-3-phos-
phate. The pentose phosphate cycle is also intercon-
nected with other pathways, related mainly to nucleotide
and lipid metabolism (not represented in Fig. 1). As hap-
pens with the Krebs cycle, the pentose phosphate cycle
may have anabolic or catabolic functions depending on
the entrance or exit of metabolites. Further metabolism of
glucose connected with the pentose phosphate cycle is
carried out by the classical glycolytic/gluconeogenic path-
ways (Fig. 1).
CALVIN CYCLE (FIG. 2)
This cycle is part of the photosynthetic CO2 fixation
carried out in the chloroplasts, vegetable cell organelles.
Chloroplasts are surrounded by a double outer membrane
and contain in their interior membrane structures called
thylakoids, which are piled up into stakes called grana.
Grana bear chlorophyll and the enzymes responsible for
the light reactions of photosynthesis leading to the syn-
thesis of ATP and NADPH. The grana are immersed in the
stroma, the gel-like matrix of the chloroplasts containing
prokaryotic DNA, RNA, 70 S ribosomes, and soluble en-
zymes implicated in several biosynthetic processes such
as fatty acids, isoprenoids, amino acids, nucleotides and
conversion of CO2 to carbohydrates, etc. This last conver-
sion, carried out with the help of ATP and NADPH gener-
ated in the photosynthetic reactions, is called the Calvin
cycle, reductive pentose phosphate pathway, or photo-
synthetic carbon reduction cycle.
275
276
FIG. 1. A three-dimensional view of the pentose phosphate
cycle. The cycle is composed of two parts: oxidative and non-
oxidative. Both parts are enclosed in a dotted line. In the first part,
glucose-6-P (G6P) is irreversible transformed into RL5P. The
non-oxidative part of the cycle is depicted with a gray background
and is carried out by enzymes catalyzing reversible reactions. The
cubic structure comprises the reaction catalyzed by transaldolase
and transketolase. The interconnections between the glycolysis
and the pentose phosphate pathways take place at the level of
glucose-6-P, fructose-6-phosphate, and glyceraldehyde-3-P.
The abbreviations correspond to the following compounds: G1P,
glucose-1-P; 2PG, 2-phosphoglycerate; PEP, phosphoenol pyru-
vate; 6PGLone, 6-phosphogluconolactone; 6PGLate, 6-phos-
phogluconate; R5P, ribose-5-P. K 18 represents the Krebs cycle.
The numbers in the figure correspond to the following enzymes:
1, glucose-6-P dehydrogenase; 2, gluconolactonase; 3, 6-P-glu-
conate dehydrogenase; 4, ribulose-5-P 3-epimerase; 5, ribulose-
5-P-isomerase; 6, transketolase; 7, transaldolase; 8, enzymes
acting in the interconversion glucose 1-P 7 glycogen; 9, phos-
phoglucomutase; 10, glucose-6-phosphatase; 11, hexokinase;
12, phosphoglucose isomerase; 13, 6-phosphofructokinase; 14,
fructose-1,6-bisphosphatase; 15, aldolase; 16, triosephosphate
isomerase; 17, glyceraldehyde-3-P dehydrogenase; 18, phos-
phoglycerate kinase; 19, phosphoglycerate mutase; 20, enolase;
21, pyruvate kinase; 22, pyruvate dehydrogenase. The reactions
catalyzed by these enzymes are specified in Table I. The parts in
gray emphasize the similarity between the pentose phosphate
and the Calvin cycles
Three phases can be considered in the Calvin cycle (Fig.
2): fixation of CO2 into 3-phosphoglycerate (3PG),1 or the
carboxylation phase; reduction of 3PG into glyceralde-
hyde-3-phosphate (GAP), or the reduction phase; and re-
synthesis of ribulose-1,5-bisphosphate, or the regenera-
tive phase. The fixation of CO2 is catalyzed by two
enzymes acting in sequence: phosphoribulose kinase (23)
1
The abbreviations used are: 3PG, 3-phosphoglycerate; GAP,
glyceraldehyde-3-P; RL5P, ribulose-5-phosphate; RL1,5P, ribu-
lose-1,5-phosphate; G6P, glucose-6-P; XL5P, xilulose 5-P; E4P,
erythrose-4-P; DHAP, dihydroxyacetone-P; F6P, fructose-6-phos-
phate; F1,6-P, fructose-1,6-bisphosphate; S1,7P, sedoheptu-
lose-1,7-bisphosphate; S7P, sedoheptulose-7-P; 1,3PG, 1,3-bis-
phosphoglycerate; Rubisco, ribulose-bisphosphate carboxylase/
oxygenase.
BAMBED, Vol. 34, No. 4, pp. 275–277, 2006
FIG. 2. A three-dimensional view of the Calvin cycle. Three
phases can be considered in this cycle. First, fixation of CO2,
carried out by enzymes 23 and 24 (see the abbreviation footnote,
Table I, the legend for Fig. 1 for the abbreviations of substrates,
name of enzymes, and reactions catalyzed). Second, reduction of
3PG, carried out by enzymes 18 and 17, with formation of GAP or
glyceraldehyde-3-P. Third, regeneration of RL5P; this part is
composed by enzymes 16, 15, 14, and 4 –7 (catalyzing similar
reactions as in the pentose phosphate cycle, see Fig. 1) and by
enzymes 23, 24, and 14 –16. These reactions occur in the stroma
part of the chloroplast. GAP can also be transported to the
cytosol where synthesis of starch (reactions 8 –11), and other
reactions (15–22) can bring GAP to the Krebs cycle or to the
synthesis of other compounds. In addition to the components of
the pentose phosphate pathway specified in Fig. 1, the following
elements participate in the Calvin cycle: (i) two more substrates,
sedoheptulose-1,7-bisphosphate (S1,7P) and RL1,5P and (ii) the
following enzymes, phosphoribulose kinase (23), Rubisco (24),
transaldolase (25), and sedoheptulose 1,7-bisphosphatase (26).
The parts in gray emphasize the similarity between the pentose
phosphate and the Calvin cycles. The reactions more directly
involved in the Calvin cycle are enclosed by a dotted line.
and ribulose-1,5-bisphosphate carboxylase, or Rubisco
(24) (Fig. 2; Table I). This enzyme constitutes of around
50% of the soluble protein in a leaf and is considered the
most abundant protein on earth. Two moles of 3PG are
formed from 1 mol of ribulose-1,5-bisphosphate.
The reduction of 3PG to GAP is catalyzed by 3-phos-
phoglycerate kinase (18) and glyceraldehyde-3-phosphate
dehydrogenase (17). Note that these two reactions are
driven in the direction of synthesis of GAP by the conver-
sion of ATP to ADP and NADPH to NADP⫹. It can be
considered that 12 mol of GAP are formed from 6 mol of
ribulose-5-P, i.e. a net gain of six carbon atoms, through the
carboxylation and reduction phases of the cycle. These 12
mol of glyceraldehyde-3-P may follow two different meta-
bolic routes: 10 mol toward the regeneration of ribulose
1,5-phosphate (RL1,5P) and 2 mol toward the synthesis of
starch or other organic compounds. The synthesis of ribu-
 277
TABLE I
Enzymes and reactions involved in the pentose phosphate and Calvin cycles
Asterisks indicate ketosugars. The number of the enzymes and the abbreviations correspond to those designed in Figs. 1 and 2. G1P,
glucose 1-P; R5P, ribose 5-P; 2PG, 2-phosphoglycerate; PEP, phosphoenol pyruvate.
Enzyme number
Pentose Phosphate Calvin cycle Enzyme name Reaction catalyzed
(Fig. 1) (Fig. 2)
1 — Glucose 6-phosphate dehydrogenase G6P ⫹ NADP⫹ 3 6-PGLone ⫹ NADPH ⫹ H⫹
2 — Gluconolactonase 6-PGone ⫹ H2O 3 6-PGLnate ⫹ H⫹
3 — 6-P-gluconate DH 6-PGLnate ⫹ NADP⫹ 3 *RL5P ⫹ NADPH ⫹ H⫹ ⫹ CO2
4 4 Ribulose 5-phosphate 3-epimerase *RL5P 7 *XL5P
5 5 Ribulose 5-phosphate isomerase *RL5P 7 R5P
6 6 Transketolase *XL5P ⫹ E4P7 GAP ⫹ *F6P
6 6 Transketolase *XL5P ⫹ R5P 7 GAP ⫹ *S7P
7 7 Transaldolase *S7P ⫹ GAP 7 *F6P ⫹ E4P
8 8 Synthesis, degradation of Glycogen/Starch G1P 7 Glycogen/Starch
9 9 Phosphoglucomutase G1P 7 G6P
10 10 Glucose 6-phosphatase G6P 3 Glucose
11 11 Hexokinase Glucose ⫹ATP 3 G6P ⫹ ADP
12 12 Phosphoglucose isomerase G6P 7*F6P
13 13 6-Phosphofructokinase *F6P ⫹ATP 3 *F1,6P ⫹ADP
14 14 Fructose bisphosphatase *F1,6P 3 *F6P ⫹Pi
15 15 Fructose bisphosphate aldolase *F1,6P ⫹ H2O7*DHAP ⫹ GAP
16 16 Triosephosphate isomerase *DHAP 7 GAP
17 — Glyceraldehyde 3-phosphate dehydrogenase GAP ⫹ NAD⫹ ⫹ Pi 7 1,3PG ⫹ NADH ⫹ H⫹
— 17 Glyceraldehyde 3-phosphate dehydrogenase GAP ⫹ NADP⫹ ⫹ Pi 7 1,3PG ⫹ NADPH ⫹ H⫹
18 18 Phosphoglycerate kinase 1,3PG ⫹ ADP 7 3PG ⫹ ATP
19 19 Phosphoglycerate mutase 3PG 7 2PG
20 20 Enolase 2PG 7 PEP ⫹ H2O
21 21 Pyruvate kinase PEP ⫹ ADP 7 Pyruvate ⫹ ATP
22 22 Pyruvate dehydrogenase complex Pyruvate ⫹ CoA ⫹ NAD⫹ 3 Acetyl-CoA ⫹ NADH ⫹
H⫹ ⫹ CO2
— 23 Phosphoribulose kinase *RL5P ⫹ ATP 3 *RL1,5P ⫹ ADP
— 24 Ribulose-bisphosphatecarboxylase (Rubisco) *RL1,5P ⫹ CO2 ⫹ H2O 3 (2) 3PG ⫹ 2 H⫹
— 25 Transaldolase *DHAP ⫹ E4P 7 *S1,7P
— 26 Sedoheptulose 1,7-bisphosphatase *S1,7P ⫹ H2O 3 *S7P ⫹ Pi

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apart in the curriculum and as if they were totally unrelated
and devoid of similarities.
Acknowledgment—We thank Javier Pérez for the drawing of
Figs. 1 and 2.
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