Cellular Respiration: Brief Look at the Citric Acid and Oxidative Phosphorylation

Just recently, I blabbed about cells and cellular respiration. Then toward the end of my last post I got really excited about cellular respiration as fundamental to all living creatures, including you and me. But all I had really talked about was the fundamental units of biological organization, the smallest living things, thermodynamics and biological chemistry, and how we get a little ATP and a bunch of energy stored as pyruvate from each glucose molecule that gets broken by glycolysis. Nothing very important, really...

Perhaps you remembered vaguely when you first learned this material. Perhaps you wondered why anyone would care. Perhaps you were amazed to be reminded of the chemical basis of all life on earth, the far-reaching implications of the chemistry which forms the foundation of biological science. If you're in the latter group, right on! And read on! Because glycolysis is only one process linked to cellular respiration. It is not considered a part of real respiration because oxygen is not involved. And it yields a relatively small amount of ATP dividends per unit starting molecule and per unit effort (10 steps, two molecules of ATP burnt off). What really gets my engine burning, and hopefully yours too, are the citric acid cycle (CAC) and oxidative phosphorylation (OP).

Before I talk about these, allow me to just say that these aren't just singular discoveries written down in books so that students get a view of the big picture from their biology education--at least, that's not all these are. Instead, the CAC and OP pathways represent active areas of scientific research. Recent studies illustrate this point: a group of scientists from Germany and other places have been looking into fluorescent imaging of CAC intermediates (here), while American scientists have examined the origin and self-organization of biochemical cycles, not to mention the evolution of the enzymes involved.

So, on to CAC and OP and what these should mean to you and me.

The CAC (Fig. 1 below) is an eight-step biochemical pathway turning pre-packaged Acetyl-CoA (a modified form of pyruvate from glycolysis; two per glucose molecule, just like pyruvate) into two molecules of CO2, three NADH, one ATP, and one FADH2 (an electron carrier similar to NADH). On the other hand, OP takes electrons from NADH and FADH2 made available from glycolysis and the citric acid cycle and uses these to generate up to 32 or 34 molecules of ATP per starting molecule of glucose!!! As an aside for now, Acetyl-CoA used in the CAC may also come from proteins and lipids--not just glucose--but this is beyond the scope of our discussion. All in all, factoring in CAC and OP in view of the classical glucose metabolism perspective, each molecule of glucose broken down in your cells has the potential to generate up to 36 or 38 molecules of ATP!!!


Figure 1. The citric acid cycle (Orgel 2000, see link at end of text).



So, we see from this overview how oxidative phosphorylation and chemiosmosis (linked processes) are together responsible for the majority of ATP produced by the respiration of our cells (eventually linked to the respiration we do with our circulatory system and respiratory systems, or blood and lungs). These ATP generated by OP and chemiosmosis are largely the result of what is known as the electron transport chain (ETC), making this one of the most important sub-cellular structures in living things.

The ETC is a collection of multiprotein complexes found all over the inner membrane of our mitochondria. NADH and FADH2 deliver electrons to specific pieces of this chain. In turn, these electrons move down the chain using well-known avenues. At the end of this chain, the last protein in the ETC sequence (these proteins are mostly particular kinds, called cytochromes. My DNA Barcoding work studies cytochrome oxidase 1 to explore nearshore fishes of the Carribbean/Western Central Atlantic for cryptic speciation events), "Cyt a3," transfers its electrons to oxygen (O2), which grabs two hydrogens to become water (H2O). Because electrons from FADH enter the ETC at a different protein complex than those donated by NADH, they provide less energy for ATP synthesis than those from NADH.

So, electrons release energy as they fall down the ETC. "But how is this energy harnessed to make ATP?" you might ask. Simple. Coupling electron transport to ATP synthesis (exergonic reactions coupled to endergonic ones, as mentioned elsewhere). This is accomplished by the process of chemiosmosis.

Chemiosmosis is the phenomenon whereby motion of an ion across its gradient through a membrane releases energy which is used to do cellular work. ATP synthase, also found in the inner wall of the mitochondrion, is the enzyme responsible for ATP formation from ADP (the "used up" form of ATP in our cells) and inorganic phosphate (P-). In the case of ATP synthase, the ion used to generate the energy of ATP regeneration is hydrogen, which accumulates in the mitochondrial intermembrane space as a result of the action of the ETC. This combined action of the ETC and chemiosmosis make up what we know as oxidative phosphorylation, what I have called OP. One key difference between this process and the ATP-yielding pathways we've discussed, glycolysis and the citric acid cycle, is that OP generates ATP from phosphorylation using these two processes instead of substrate-level phosphorylation, the method of glycolysis and CAC. Are you with me??

Hope so.


There you have it... in a nutshell, the difference between glycolysis and cellular respiration, the difference between glycolysis/CAC and oxidative phosphorylation (ETC + chemiosmosis/ATP synthesis), and all fit into an overview of how we get chemical energy from our food. Holla!

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See Campbell and Reece (2007) for more information, or try a search of Google Scholar to learn more about cellular respiration, glycolysis, the CAC or OP. Or, read this Orgel (2000) paper. Peace out ~ JB