Ascorbate functions as a cofactor in the enzymatic hydroxylation catalyzed by Fe 2+/αKG-dependent dioxygenases prolyl 4-hydroxylase, prolyl 3-hydroxylase and lysyl hydroxylase ( Myllylä et al., 1984 Peterkofsky, 1991 Pekkala et al., 2003 Padayatty and Levine, 2016) through the reduction of Fe 3+ to the active Fe 2+ ( de Jong et al., 1982 Gorres and Raines, 2010).
MIGUEL WILD HEART ZIP SKIN
One of the main symptoms in scurvy is skin impairment and injuries due to the involvement of ascorbate in the biosynthesis and stability of collagen. Thus, that molecule, previously called hexuronic acid, was renamed as ascorbic acid. In the earlies 1930’s, Albert Szent-Györgyi identified and isolated the molecule responsible for this anti-scurvy activity.
Thus, this disease was typically manifested during long sea travels with a diet scarce in fresh vegetables and fruits. However, this was not obvious at the time because the lack of ascorbate in the diet takes about a month before the symptoms to occur. The role of ascorbate in mammals has extensively been studied throughout time, particularly since the 18th century with the discovery of its role in preventing scurvy ( Lind, 1753 Baron, 2009). Thus, this molecule must be incorporated in the diet (hence classified as a vitamin), with vegetables and fruits as the major sources of ascorbate. Dietary changes with the inclusion of abundant fruits and vegetables in the diet resulted in the loss of selective pressure to keep the pathway functional ( Macknight et al., 2017). While many animals are able to synthesize ascorbate in the liver or in the kidney, others, such as humans, non-human primates, guinea pigs, and certain groups of bats and birds have lost this ability due to the accumulation of mutations in the coding sequence of the last committed enzyme of the pathway (L-gulono-1,4-lactone oxidase, GULO Chatterjee, 1973 Nishikimi et al., 1994 Drouin et al., 2011). L-Ascorbic Acid (L-threo-hex-2-enono-1,4-lactone, ascorbate), also called vitamin C, is an essential antioxidant molecule in plant and animal metabolism and also functioning as a cofactor in many enzymes. We here review the regulation of ascorbate synthesis, its close connection with the cell wall, as well as different strategies to increase its content in plants, with a special focus on fruits. In certain fruits and developmental conditions, an alternative pathway from D-galacturonate might be also relevant. This is likely to involve a yet unknown tight regulation enabling plant growth and development, without impairing the cell redox state modulated by ascorbate pool.
Therefore, a better understanding of ascorbate biosynthesis and regulation is essential for generation of improved fruits without developmental side effects. Two intermediates of the Smirnoff-Wheeler pathway, GDP-D-mannose and GDP-L-galactose, are also precursors of the non-cellulosic components of the plant cell wall. Plants synthesize ascorbate de novo mainly through the Smirnoff-Wheeler pathway, the dominant pathway in photosynthetic tissues. Several attempts to increase ascorbate in fruits have achieved fairly good results but, in some cases, detrimental effects in fruit development also occur, likely due to the interaction between the biosynthesis of ascorbate and components of the cell wall. Nowadays, there is an increasing interest to boost ascorbate content, not only to improve fruit quality but also to generate crops with elevated stress tolerance. Although fruits and vegetables constitute the main source of ascorbate in the human diet, rising its content has not been a major breeding goal, despite the large inter- and intraspecific variation in ascorbate content in fruit crops. In addition to its main role as an antioxidant and cofactor in redox reactions, recent reports have shown an important role of ascorbate in the activation of epigenetic mechanisms controlling cell differentiation, dysregulation of which can lead to the development of certain types of cancer.
Throughout evolution, a number of animals including humans have lost the ability to synthesize ascorbic acid (ascorbate, vitamin C), an essential molecule in the physiology of animals and plants.