Biosynthesis of camptothecin. In silico and in vivo tracer study from [1-13C]glucose. 2004

Yasuyo Yamazaki, and Mariko Kitajima, and Masanori Arita, and Hiromitsu Takayama, and Hiroshi Sudo, and Mami Yamazaki, and Norio Aimi, and Kazuki Saito
Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.

Camptothecin derivatives are clinically used antitumor alkaloids that belong to monoterpenoid indole alkaloids. In this study, we investigated the biosynthetic pathway of camptothecin from [1-13C]glucose (Glc) by in silico and in vivo studies. The in silico study measured the incorporation of Glc into alkaloids using the Atomic Reconstruction of Metabolism software and predicted the labeling patterns of successive metabolites from [1-13C]Glc. The in vivo study followed incorporation of [1-13C]Glc into camptothecin with hairy roots of Ophiorrhiza pumila by 13C nuclear magnetic resonance spectroscopy. The 13C-labeling pattern of camptothecin isolated from the hairy roots clearly showed that the monoterpene-secologanin moiety was synthesized via the 2C-methyl-D-erythritol 4-phosphate pathway, not via the mevalonate pathway. This conclusion was supported by differential inhibition of camptothecin accumulation by the pathway-specific inhibitors (fosmidomycin and lovastatin). The quinoline moiety from tryptophan was also labeled as predicted by the Atomic Reconstruction of Metabolism program via the shikimate pathway. These results indicate that camptothecin is formed by the combination of the 2C-methyl-D-erythritol 4-phosphate pathway and the shikimate pathway. This study provides the innovative example for how a computer-aided comprehensive metabolic analysis will refine the experimental design to obtain more precise biological information.

UI MeSH Term Description Entries
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D010427 Pentose Phosphate Pathway An oxidative decarboxylation process that converts GLUCOSE-6-PHOSPHATE to D-ribose-5-phosphate via 6-phosphogluconate. The pentose product is used in the biosynthesis of NUCLEIC ACIDS. The generated energy is stored in the form of NADPH. This pathway is prominent in tissues which are active in the synthesis of FATTY ACIDS and STEROIDS. Hexose Monophosphate Shunt,Pentose Phosphate Shunt,Pentose Shunt,Pentosephosphate Pathway,Pentose-Phosphate Pathway,Pentosephosphate Shunt,Hexose Monophosphate Shunts,Pathway, Pentose Phosphate,Pathway, Pentose-Phosphate,Pathway, Pentosephosphate,Pathways, Pentose Phosphate,Pathways, Pentose-Phosphate,Pathways, Pentosephosphate,Pentose Phosphate Pathways,Pentose Phosphate Shunts,Pentose Shunts,Pentose-Phosphate Pathways,Pentosephosphate Pathways,Pentosephosphate Shunts,Shunt, Hexose Monophosphate,Shunt, Pentose,Shunt, Pentose Phosphate,Shunt, Pentosephosphate,Shunts, Hexose Monophosphate,Shunts, Pentose,Shunts, Pentose Phosphate,Shunts, Pentosephosphate
D002166 Camptothecin An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA TOPOISOMERASES, TYPE I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. Camptothecine
D002247 Carbon Isotopes Stable carbon atoms that have the same atomic number as the element carbon but differ in atomic weight. C-13 is a stable carbon isotope. Carbon Isotope,Isotope, Carbon,Isotopes, Carbon
D002952 Citric Acid Cycle A series of oxidative reactions in the breakdown of acetyl units derived from GLUCOSE; FATTY ACIDS; or AMINO ACIDS by means of tricarboxylic acid intermediates. The end products are CARBON DIOXIDE, water, and energy in the form of phosphate bonds. Krebs Cycle,Tricarboxylic Acid Cycle,Citric Acid Cycles,Cycle, Citric Acid,Cycle, Krebs,Cycle, Tricarboxylic Acid,Cycles, Citric Acid,Cycles, Tricarboxylic Acid,Tricarboxylic Acid Cycles
D003198 Computer Simulation Computer-based representation of physical systems and phenomena such as chemical processes. Computational Modeling,Computational Modelling,Computer Models,In silico Modeling,In silico Models,In silico Simulation,Models, Computer,Computerized Models,Computer Model,Computer Simulations,Computerized Model,In silico Model,Model, Computer,Model, Computerized,Model, In silico,Modeling, Computational,Modeling, In silico,Modelling, Computational,Simulation, Computer,Simulation, In silico,Simulations, Computer
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D006019 Glycolysis A metabolic process that converts GLUCOSE into two molecules of PYRUVIC ACID through a series of enzymatic reactions. Energy generated by this process is conserved in two molecules of ATP. Glycolysis is the universal catabolic pathway for glucose, free glucose, or glucose derived from complex CARBOHYDRATES, such as GLYCOGEN and STARCH. Embden-Meyerhof Pathway,Embden-Meyerhof-Parnas Pathway,Embden Meyerhof Parnas Pathway,Embden Meyerhof Pathway,Embden-Meyerhof Pathways,Pathway, Embden-Meyerhof,Pathway, Embden-Meyerhof-Parnas,Pathways, Embden-Meyerhof
D014364 Tryptophan An essential amino acid that is necessary for normal growth in infants and for NITROGEN balance in adults. It is a precursor of INDOLE ALKALOIDS in plants. It is a precursor of SEROTONIN (hence its use as an antidepressant and sleep aid). It can be a precursor to NIACIN, albeit inefficiently, in mammals. Ardeydorm,Ardeytropin,L-Tryptophan,L-Tryptophan-ratiopharm,Levotryptophan,Lyphan,Naturruhe,Optimax,PMS-Tryptophan,Trofan,Tryptacin,Tryptan,Tryptophan Metabolism Alterations,ratio-Tryptophan,L Tryptophan,L Tryptophan ratiopharm,PMS Tryptophan,ratio Tryptophan
D057888 Iridoid Glucosides A subclass of iridoid compounds that include a glucoside moiety, usually found at the C-1 position. Iridoid Glucoside,Iridoidglucoside,Secoiridoid Glucoside,Iridoidglucosides,Secoiridoid Glucosides,Glucoside, Iridoid,Glucoside, Secoiridoid,Glucosides, Iridoid,Glucosides, Secoiridoid

Related Publications

Yasuyo Yamazaki, and Mariko Kitajima, and Masanori Arita, and Hiromitsu Takayama, and Hiroshi Sudo, and Mami Yamazaki, and Norio Aimi, and Kazuki Saito
February 1977, The Journal of laboratory and clinical medicine,
Yasuyo Yamazaki, and Mariko Kitajima, and Masanori Arita, and Hiromitsu Takayama, and Hiroshi Sudo, and Mami Yamazaki, and Norio Aimi, and Kazuki Saito
November 1995, Biological & pharmaceutical bulletin,
Yasuyo Yamazaki, and Mariko Kitajima, and Masanori Arita, and Hiromitsu Takayama, and Hiroshi Sudo, and Mami Yamazaki, and Norio Aimi, and Kazuki Saito
July 1983, Analytical biochemistry,
Yasuyo Yamazaki, and Mariko Kitajima, and Masanori Arita, and Hiromitsu Takayama, and Hiroshi Sudo, and Mami Yamazaki, and Norio Aimi, and Kazuki Saito
October 2006, Journal of magnetic resonance (San Diego, Calif. : 1997),
Yasuyo Yamazaki, and Mariko Kitajima, and Masanori Arita, and Hiromitsu Takayama, and Hiroshi Sudo, and Mami Yamazaki, and Norio Aimi, and Kazuki Saito
June 2005, Magnetic resonance in medicine,
Yasuyo Yamazaki, and Mariko Kitajima, and Masanori Arita, and Hiromitsu Takayama, and Hiroshi Sudo, and Mami Yamazaki, and Norio Aimi, and Kazuki Saito
June 1995, Journal of neurochemistry,
Yasuyo Yamazaki, and Mariko Kitajima, and Masanori Arita, and Hiromitsu Takayama, and Hiroshi Sudo, and Mami Yamazaki, and Norio Aimi, and Kazuki Saito
July 2022, Cancer & metabolism,
Yasuyo Yamazaki, and Mariko Kitajima, and Masanori Arita, and Hiromitsu Takayama, and Hiroshi Sudo, and Mami Yamazaki, and Norio Aimi, and Kazuki Saito
January 1980, European journal of biochemistry,
Yasuyo Yamazaki, and Mariko Kitajima, and Masanori Arita, and Hiromitsu Takayama, and Hiroshi Sudo, and Mami Yamazaki, and Norio Aimi, and Kazuki Saito
June 2010, Magnetic resonance imaging,
Yasuyo Yamazaki, and Mariko Kitajima, and Masanori Arita, and Hiromitsu Takayama, and Hiroshi Sudo, and Mami Yamazaki, and Norio Aimi, and Kazuki Saito
April 2019, Fitoterapia,
Copied contents to your clipboard!