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Physiological constraints on evolution of enzymes for cellular metabolic pathways

✍ Scribed by D.K. Srivastava


Publisher
Elsevier Science
Year
1991
Tongue
English
Weight
681 KB
Volume
152
Category
Article
ISSN
0022-5193

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✦ Synopsis


The review article by Ov~idi (1991) provides an up-to-date summary of current understanding about metabolite channeling between enzyme pairs. In recent years, several such articles have appeared (as reviewed by Ov~idi) suggesting the importance of metabolite channeling and enzyme organization for cellular metabolic pathways, and this article is merely a repetition of its predecessors. The major deficiency is that its main body of text is not apropos to the elegant title "physiological significance...".

Dr Ov~idi is one of the leading experts in the area of metabolite channeling, and as a proponent of the overall concept I do not have any fundamental disagreement with her views. However, I have several conceptual differences throughout the entire article. For example, at the beginning of the review, Ovfidi states "This extremely high macromolecular concentration crowding of the cell influences biorecognition process and leads to the formation of protein complexes". I entirely disagree with this concept. The molecular crowding, as such, cannot influence biorecognition, neither can crowding promote protein complexes. The biorecognition must arise as a result of surface complementarity of the macromoleclar components of the cell, rather than as a result of higher protein concentrations; the latter can only influence thermodynamic distribution between complexed and uncomplexed states of macromolecules. Likewise, I do not agree with the proposition that there is a catalytic advantage due to higher concentration effect of an enzyme-bound substrate in other enzyme catalyzed reactions. Were this to be the case, similar effects would have been observed at high concentrations of aqueous substrates, without any influence of enzyme-enzyme interactions.

Besides some disagreements like these, I note that some important considerations of physiological systems have been completely ignored by Ov~di. For example, there is hardly any mention of regulatory importance of metabolite channeling under physiological conditions. Such discussions would have been of significant interest from a "physiological significance..." point of view. In addition, there is a miscomprehension among enzymologists, particularly those who do not believe in metabolic organization, that every specialized mechanism related to enzyme systems is evolved to enhance their catalytic rates. Such concepts are not surprising, since enzymes have been historically recognized as true catalysts of biochemical reaction pathways. Keeping these weaknesses in mind, I would like to share some of my ideas (gathered and matured during last 8 years of active participation in this area) in conjunction with the themes presented by Ovfidi. In this way, my commentary is more like a supplement to this article.