Metabolic design principles: Chemical and physical determinants of cell chemistry

Abstract

SummaryBiochemical defense can be viewed, not only as mechanisms that deal with toxicmolecules and with the consequences of damage to macromolecules but, also, to a setof design principles that ensures that the occurrence of unwanted outcomes isminimized, or even eliminated. Such design principles include those responsible forthe conservation of solvent capacity, the maintenance of constant osmotic pressure,and the avoidance of unwanted reactions and of unnecessary increases in body mass.Unwanted reactions are minimized by means of very low concentrations ofmetabolic intermediates as well as by the avoidance of highly reactive intermediates,such as aldehydes. This may have favored the selection of glucose as the principalmonosaccharide in animals as it has the lowest proportion of straight-chain structure(and, therefore, of free aldehyde groups) of all the aldohexoses. Glycogen may havebeen selected as the major storage form of carbohydrate because (i) its a-1,4-glycosidic linkages ensure that it has no free aldehyde groups, and (ii) its polymericnature exerts almost no osmotic pressure. The conservation of solvent capacity isfacilitated by the use of activated intermediates that drive reactions at very lowconcentrations of intermediates. The avoidance of unnecessary increases in mass isfacilitated by the utilization of fat, rather than carbohydrate, as our principal caloricstore.AcknowledgmentsThe author’s work is supported by grants from the Canadian Institutes for HealthResearch and by the Canadian Diabetes Association. JTB is a Senior Investigator ofthe Canadian Institutes for Health Research.References