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Is there any evolutionary reason for glucose being the "main" molecule used as a source of energy, beginning with glycolysis and subsequently cellular respiration (after being converted to two pyruvate molecules)? Or did this particular biochemical pathway arise "by fluke" early on in the history of life?

A colleague of mine told me that it was because as shown below, all of beta-D-glucose's hydroxyl substituents are all equatorially positioned (when in the correct chair conformation), which lends to its general stability.

Beta-D-Glucose Image taken from the Wikimedia Commons.

Could this have played a factor in the beginnings of energy metabolism, and if so, why?

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I don't have a direct answer for you, but you should try to get hold of a copy of Romano AH, Conway T. (1996). "Evolution of carbohydrate metabolic pathways". – Polynomial Jul 20 '12 at 7:48
up vote 7 down vote accepted

I thought this was a great question. In particular because it hints at two questions. The first is 'why carbohydrates are used to store energy' in general. The second being 'why glucose rather than other carbohydrates?' in particular.

Glucose metabolism (and glycogen storage) is a core gene pathway - its found in bacteria archaea and eukaryotes. So probably the most that we can readily say about question one is that as @rwst points out this pathway has proven to be useful at a critical juncture of the formulation of living things on earth. If you look at glucose metabolism pathways, you can see that glycerate compounds and pyruvate are the actual intermediates that are used to create energy. The first thing about these molecule worth noting is that they have a good mix of carbon and oxygen, which would make it easier to extract energy - creating CO2 from these compounds may even predates the existence of atmospheric oxygen. So glucose and fructose (which is actually derived from glucose in the metabolic pathway) are actually storage molecules themselves, easily broken down to smaller molecules.

As to the second question: there are quite a few ways to arrange oxygen around the carbohydrate ring. why glucose? The advantages of glucose is probably a subtle one. The structural properties of glycogen might be a reason that the use of glucose monomer is so important for glycogen. There is no evidence that I can find for this, so its always possible that glucose was just the first hexose carbohydrate to be biologically used. Its sort of hard to imagine that the structure of glucose does not play some sort of role in cell structure though.

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One could argue ATP is used to store energy, glucose is just the means to get this energy into ATP. Semantics, I know. – nico Jul 27 '12 at 6:18
true - in this case we're trying to dissect the question in terms of which is oldest/ most primal. from a molecular biology standpoint ATP is often a better answer. – shigeta Jul 27 '12 at 16:48
Looking at this question again, ATP does not really store energy - its a high energy currency used throughout the cell, but its used and turned over rapidly in the mitochondria. a human body has 250 g of ATP at any given moment but uses its own weight of ATP every day: – shigeta Feb 16 '14 at 20:05

This is only a guess but I hope somewhat educated, so refute me. The establishment of glucose as nutritional molecule is mainly linked with the availability of carbohydrates in the environment, i.e. plants as nutrition. Before plants evolved however, there were only bacteria and they use glucose as one of many oligosaccharides. But more important than glucose is trehalose because it is less toxic and can be collected in large amounts in the cell. The only reserves for glucose are glycogen and the bacterial cell wall which can be catabolized. So, in my guess, the reason for the mere existence of glycolysis/gluconeogenesis pathways is the bacterial cell wall that has to be synthesized and catabolized. Only later were these pathways differentiated when land plants came up and animals that et them.

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that's an interesting argument. if you could demonstrate somehow that glucose is what plants prefer to make for some good reason, it would really reinforce the hypothesis... – shigeta Jul 27 '12 at 16:49
Remember that land plants stem from green algae that were bacteria earlier. Green algae had not much of a glucose preference but they developed starch as an efficient reserve, in addition to glycogen and trehalose. Only when land plants needed thick cell walls and big structures, glucose needed to be produced en masse. – rwst Jul 27 '12 at 17:39

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