- Email: [email protected]
The last frontier: the road to the C
FORUM
The last frontier: the road to the C he role of ascorbic acid, vitamin T C, in human health has for many years been a matter for discussion. Linus Pauling for example, advocated the daily intake of large amounts of ascorbate, and there is certainly a widely held view that it helps in the immune response to viruses such as the common cold, but others have been less easily persuaded of its role in increasing the effectiveness of the immune system. More recent research has, however, described a role for ascorbate as an antioxidant, one of a suite of compounds that protect cells from oxidative stress. Whatever the exact role of ascorbate, the effects of its lack have been known directly or indirectly for a very long time. The inclusion of limes in ships’ provisions, long before ascorbate had been identified, was based on the knowledge that lack of fruit and vegetables in the diet led to conditions such as scurvy. Today, among the general public, it is probably one of the most widely known plant-biochemical facts that fresh fruit and vegetables are good sources of vitamin C. This view is clearly supported by the data: in green leaves, L-ascorbate can constitute up to 10% of the soluble carbohydrate pool. It is one of those oddities of evolution that, even though ascorbate is essential to our health, humans (and a handful of other animals) are unable to synthesize it, leading to our
dependence on dietary sources. It is also one of the interesting facets of scientific progress that, even though the biosynthetic pathway of ascorbate in those animals that can make it was elucidated several years ago, the biosynthetic pathway in plants was, until very recently, not known. It is intriguing that a pathway that is a major part of plant metabolism and has significant relevance to human health should have remained a mystery for so long. The biosynthesis by plants of ascorbate is thus the last major pathway in plant metabolism to give up its secrets. That it has done so may be largely attributed to the recent work of Smirnoff and co-workers1. The first major clue to understanding the biosynthesis of ascorbate came from work in the 1950s, demonstrating that plants possess an enzyme that efficiently converts L-galactono-1,4-lactone directly to ascorbate2. However, despite extensive further work, particularly by Loewus and co-workers3, the natural precursors for the lactone remained unknown. It was the demonstration by Smirnoff and co-workers that L-galactose is an efficient precursor for ascorbate in both Arabidopsis and pea that led finally to our understanding of the pathway. Smirnoff et al. went on to discover a previously unknown enzyme, L-galactose dehydrogenase, which converts L-galactose to L-galactono-1,4-lactone,
the immediate precursor of ascorbate. From there, the pathway was traced backwards by a combination of detailed analysis following the feeding of radioactive intermediates and demonstration of the required enzyme activities. The specific details of the pathway are not our concern here but suffice it to say that the work clearly demonstrated that plants can synthesize L-galactose from D-mannose-1-phosphate (in four steps) without inversion of the hexose carbon skeleton (the latter point being established by Loewus3). The elucidation of a major metabolic pathway is an achievement in itself but there are also clear biotechnological implications of this work. As Smirnoff and his colleagues state in their paper1, ‘We are now in a position to … manipulate [ascorbate’s] content with potential benefits for human nutrition and plant resistance to oxidative stress.’ Identification of the genes encoding the key enzymes in the pathway will be an essential step in achieving this aim.
Letter
References 1 Wheeler, G. L., Jones, M. A. and Smirnoff, N. (1998) Nature 393, 365–369 2 Mapson, L. W. and Breslow, E. (1958) Biochem. J. 68, 395–406 3 Loewus, F. A. and Loewus, M. B. (1987) Crit. Rev. Plant Sci. 5, 101–119
John A. Bryant Department of Biological Sciences, University of Exeter, Washington Singer Labs, Perry Road, Exeter, UK EX4 4QG. (E-mail: [email protected])
Letters to the Editor Trends in Biotechnology welcomes letters to the Editor that address issues raised in recent TIBTECH articles, or issues related to current developments in biotechnology that are of broad interest to the biotechnology community. Letters should normally be supported by reference to published work. Please address letters to: Dr Meran Owen (Editor) Trends in Biotechnology, Elsevier Trends Journals, 68 Hills Road, Cambridge, UK CB2 1LA. Please mark clearly whether or not the letter is intended for publication.
TIBTECH NOVEMBER 1998 (VOL 16)
Copyright © 1998, Elsevier Science Ltd. All rights reserved. 0167 – 7799/98/$19.00. PII: S0167-7799(98)01238-4
449
The last frontier: the road to the C he role of ascorbic acid, vitamin T C, in human health has for many years been a matter for discussion. Linus Pauling for example, advocated the daily intake of large amounts of ascorbate, and there is certainly a widely held view that it helps in the immune response to viruses such as the common cold, but others have been less easily persuaded of its role in increasing the effectiveness of the immune system. More recent research has, however, described a role for ascorbate as an antioxidant, one of a suite of compounds that protect cells from oxidative stress. Whatever the exact role of ascorbate, the effects of its lack have been known directly or indirectly for a very long time. The inclusion of limes in ships’ provisions, long before ascorbate had been identified, was based on the knowledge that lack of fruit and vegetables in the diet led to conditions such as scurvy. Today, among the general public, it is probably one of the most widely known plant-biochemical facts that fresh fruit and vegetables are good sources of vitamin C. This view is clearly supported by the data: in green leaves, L-ascorbate can constitute up to 10% of the soluble carbohydrate pool. It is one of those oddities of evolution that, even though ascorbate is essential to our health, humans (and a handful of other animals) are unable to synthesize it, leading to our
dependence on dietary sources. It is also one of the interesting facets of scientific progress that, even though the biosynthetic pathway of ascorbate in those animals that can make it was elucidated several years ago, the biosynthetic pathway in plants was, until very recently, not known. It is intriguing that a pathway that is a major part of plant metabolism and has significant relevance to human health should have remained a mystery for so long. The biosynthesis by plants of ascorbate is thus the last major pathway in plant metabolism to give up its secrets. That it has done so may be largely attributed to the recent work of Smirnoff and co-workers1. The first major clue to understanding the biosynthesis of ascorbate came from work in the 1950s, demonstrating that plants possess an enzyme that efficiently converts L-galactono-1,4-lactone directly to ascorbate2. However, despite extensive further work, particularly by Loewus and co-workers3, the natural precursors for the lactone remained unknown. It was the demonstration by Smirnoff and co-workers that L-galactose is an efficient precursor for ascorbate in both Arabidopsis and pea that led finally to our understanding of the pathway. Smirnoff et al. went on to discover a previously unknown enzyme, L-galactose dehydrogenase, which converts L-galactose to L-galactono-1,4-lactone,
the immediate precursor of ascorbate. From there, the pathway was traced backwards by a combination of detailed analysis following the feeding of radioactive intermediates and demonstration of the required enzyme activities. The specific details of the pathway are not our concern here but suffice it to say that the work clearly demonstrated that plants can synthesize L-galactose from D-mannose-1-phosphate (in four steps) without inversion of the hexose carbon skeleton (the latter point being established by Loewus3). The elucidation of a major metabolic pathway is an achievement in itself but there are also clear biotechnological implications of this work. As Smirnoff and his colleagues state in their paper1, ‘We are now in a position to … manipulate [ascorbate’s] content with potential benefits for human nutrition and plant resistance to oxidative stress.’ Identification of the genes encoding the key enzymes in the pathway will be an essential step in achieving this aim.
Letter
References 1 Wheeler, G. L., Jones, M. A. and Smirnoff, N. (1998) Nature 393, 365–369 2 Mapson, L. W. and Breslow, E. (1958) Biochem. J. 68, 395–406 3 Loewus, F. A. and Loewus, M. B. (1987) Crit. Rev. Plant Sci. 5, 101–119
John A. Bryant Department of Biological Sciences, University of Exeter, Washington Singer Labs, Perry Road, Exeter, UK EX4 4QG. (E-mail: [email protected])
Letters to the Editor Trends in Biotechnology welcomes letters to the Editor that address issues raised in recent TIBTECH articles, or issues related to current developments in biotechnology that are of broad interest to the biotechnology community. Letters should normally be supported by reference to published work. Please address letters to: Dr Meran Owen (Editor) Trends in Biotechnology, Elsevier Trends Journals, 68 Hills Road, Cambridge, UK CB2 1LA. Please mark clearly whether or not the letter is intended for publication.
TIBTECH NOVEMBER 1998 (VOL 16)
Copyright © 1998, Elsevier Science Ltd. All rights reserved. 0167 – 7799/98/$19.00. PII: S0167-7799(98)01238-4
449