On the evolution of the glycolytic pathway (glycolysis)

Jonathan McLatchie has a PhD in Evolutionary Biology from Newcastle University (UK) and he is currently "resident biologist" and a fellow at the Center for Science and Culture at the Discovery Institute. He is an intelligent design creationist who attacks evolution by questioning standard explanations in the fields of biochemistry and molecular biology.

I've debated him frequently over the years since those are my areas of interest as well. The last time we met was at an evolution conference in London (UK) in 2016 (see photo).

I've always found Jonathan to be more honest and more willing to learn than most of his creationist colleagues so that's why I'm addressing his latest post on Evolution News (sic) where he challenges the evolutionary origins of the glycolytic pathway. As you might expect, his argument is largely based on the idea that since the glycolytic pathway is very complicated, there's no way it could have arisen all at once. He then goes on to reject the idea that the pathway could have evolved incrementally, one step at a time.

There's a major flaw in Jonathan's argument and that's what I want to address in this post. You'll have to pay attention because he's making the same false assumptions that many of you might also have been taught in your biochemistry courses.

I'll be relying on figures and text from my textbook to make the case for the evolution of the glycolytic pathway so there's going to be some hard-core biochemistry with structures and reactions—it's too bad that Jonathan McLatchie didn't read my textbook before he posted or he might have saved himself some embarrassment.

Jonathan begins his critique with a false statment.

Glycolysis has been proposed to be the first biochemical pathway to arise in evolution. Among the reasons for this are the fact that glycolysis is found ubiquitously across the tree of life (so may be inferred to have been present in the last universal common ancestor).

The glycolytic pathway is NOT ubiquitous. There are many species of bacteria that are missing one or more of the key enzymes of glycolysis so they cannot degrade glucose via the standard glycolytic pathway. It cannot be the first biochemical pathway to arise in evolution because in order to degrade glucose you have to have glucose molecules to degrade and no serious scientist thinks that life arose in a sweet soup of spontaneously-created glucose molecules.

I've addressed this point in the past [Where did the glucose come from?] [More primordial soup nonsense]. The key point is that the first pathway was gluconeogenesis, or the SYNTHESIS of glucose from pyruvate. It was only after glucose became useful as a storage molecule in the form of glycogen (a polymer of glucose residues) that the breakdown of glucose to get energy became useful. Every free-living species has the gluconeogenesis pathway because that's the ubiquitous pathway and glucose synthesis evolved before glucose degradation.

Here's a figure from my textbook showing the two pathways. Gluconeogenesis (blue, bottom to top) begins with pyruvate and ends with glucose-6-phosphate, which can be polymerized to form glycogen. There is an enzyme that can convert it to free glucose but that doesn't happen in most cells. The glycolysis pathway begins with glucose-6-phosphate in most cells (red, top to bottom) but some species, notably animals, can encounter free glucose that's converted to glucose-6-phosphate by hexokinase.

University biochemistry courses are mostly taught as human biochmistry so students will be prepared for medical school. Thus, most biochemistry students see free glucose as an energy source but that's only true for animals. Bacteria, most protozoa, algae, plants, and many fungi do not encounter free external glucose so the only source of glucose is those molecules that they make for themselves via gluconeogenesis. I think this is the source of the misconception that glycolysis is the most primitive pathway.

Our current understanding of the origin of life points to the gradual evolution of pathways involving simple carbon molecules such as pyruvate, acetate, and oxaloacetate. Over time, additional pathways to more complex molecules evolved and this led to production of phosphoenolpyruvate and 3-phosphoglycerate, which are substrates for synthesis of amino acids such as phenylalanine, tryptophan, tyrosine, serine, serine, and glycine. Eventually the pathway was extended to include glucose-6-phosphate.

Note that biochemical reactions are reversible so all of the gluconeogenesis rections can also serve as a pathway for degradation of glucose. However, in practice, the equilibrium concentrations of some of the reactions are much more favorable for gluconeogenesis than glycolysis so that after the evolution of the gluconeogenesis pathway additional enzymes were required to make glycolysis feasible. The most important point is that you can't evolve glycolysis unless you have glucose and glucose only became available after the gluconeogenesis pathway evolved. This mistake by McLathie makes his entire argument worthless.

He could have learned this from reading page 356 in my textbook.

Although all species have a gluconeogenesis pathway, they don't all have the glycolysis pathway. This is especially true of bacterial species that diverged very early in the evolution of prokaryotes. Thus, it seems like gluconeogenesis is the more ancient pathway, which makes sense since there has to be a source of glucose before pathways for its degradation can evolve. Since the biosynthesis pathway evolved first, it is appropariate to think of the glycolytic enzymes as bypass enzymes. These enzymes, especially phosphofructokinase-1, evolved in order to bypass the metabolically irreversible reactions of gluconeogenesis.

It turns out that glycolysis isn't even the first pathway that evolved in order to degrade glucose. I explained this on page 351.

The classic glycolysis pathway is also called the Embden–Meyerhof–Parnas pathway. This pathway is found in all eukaryotes and many species of bacteria. However, a large number of bacterial species do not have phosphofructokinase-1 and cannot convert glucose 6-phosphate to fructose 1,6-bisphosphate in the hexose stage of glycolysis.

The hexose stage of classic glycolysis can be bypassed by the Entner–Doudoroff pathway (right). This pathway begins with the conversion of glucose 6-phosphate to 6-phosphogluconate, a reaction that is catalyzed by two enzymes: glucose 6-phosphate dehdrogenase and 6-phosphogluconolactonase. The oxidation of glucose-6-phosphate by glucose 6-phosphate dehydrogenase is coupled to the reduction of NADP⁺. The dehydrogenase and 6-phosphogluconolactonase enzymes are common in almost all species since they are required in the pentose phosphate pathway. The Entner–Douderoff pathway is the earliest pathway for glucose degradation. The classic glycolysis pathway (EMP) evolved later.

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