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picture taken from Molecular Biology of the Cell, 6th ed. by Alberts et al

It seems that there are four hydrogen atoms in alpha-ketoglutarate and one in HS-CoA (not counting the ones in CoA), five in total. Two of them go to NADH and H+, so there should be three atoms in succynyl-CoA instead of four. What am I missing here?

picture taken from Molecular Biology of the Cell, 6th ed., by Alberts et al.

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  • $\begingroup$ Where are you getting "Two of them go to NADH and H+" from? Count the carbons on each side of the reaction, including CO2. $\endgroup$ – Maximilian Press May 26 at 23:20
  • $\begingroup$ There are 5 of them on each side (not including the ones in CoA). But there is one more proton (H+) on the right side of reaction, and that's what seems problematic to me, that is, reaction would make more sense to me if the product contained NADH, not NADH + H+. $\endgroup$ – Kristaps Čivkulis May 26 at 23:24
  • $\begingroup$ Oops, for some reason I read "hydrogen" as "carbon"- my bad. $\endgroup$ – Maximilian Press May 27 at 5:52
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Short answer:

There should have been an additional $\text{H}^+$ on the left-hand side.

Long answer:

You have rightly observed that the left side of the equation is deficient in one hydrogen atom. Let me draw your attention to another issue: the charges on both sides are different too. The left side has one negative charge too many. This gives us a clue: possibly there is a missing $\text{H}^+$ on the left.

This reaction is actually the sum of three reactions catalysed by a multi-enzyme complex. If you add the balanced equations for the reactions of $\alpha$-ketoglutarate dehydrogenase, dihydrolipoyl transsuccinylase and dihydrolipoyl dehydrogenase, you will see that there is indeed an additional $\text{H}^+$ on the left-hand side, which is omitted in your textbook.

But that is the case with most biochemistry/molecular biology texts. Biologists are very bad at balancing their equations, especially when it comes to $\text{H}^+$ and $\text{H}_2 \text{O}$. They balance out only the major reactants and products. The rest is often, er, left as an exercise to the reader.

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    $\begingroup$ Lodish is a Molecular Biology book. Berg et al., which is a biochemistry book, has it right (i.e. no hydrogen ions at all). However, heaven preserve us from chemistry students who can’t see what’s important in biochemical pathways because all they understand about chemistry is balancing equations. $\endgroup$ – David May 27 at 14:14
  • $\begingroup$ Sorry Alberts — molecular or cellular biology. But not biochemistry. $\endgroup$ – David May 27 at 18:52
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NAD+ accepts only one hydrogen ion (H+) and two electrons (2e−), to form NADH + H+. So only one Hydrogen is used by NAD+, and remaining four are present in Succinyl CoA.

The reaction mentioned in your question is a three step reaction involving decarboxylation of α-ketoglutarate, reduction of NAD+ to NADH, and at last formation of Succinyl CoA. Last step also uses FADH2.

enter image description here

Reference:

http://www.phschool.com/science/biology_place/biocoach/cellresp/closer2.html https://www.elysiumhealth.com/en-us/science-101/whats-the-difference-between-nad-and-nadh

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  • $\begingroup$ I am confused. In your second reference the illustration "NAD+ to NADH redox reaction" clearly shows that NAD+ together with 2e- and H+ forms NADH, not NADH and H+, as you claim in your answer. $\endgroup$ – Kristaps Čivkulis May 26 at 19:03
  • $\begingroup$ As this is an redox reaction the two electrons balances out the reaction, which is normally shown, but here they have not shown the electrons. $\endgroup$ – Twinkle Sheen May 26 at 20:33
  • $\begingroup$ And this is a multistep reaction using FADH2 also. $\endgroup$ – Twinkle Sheen May 26 at 20:55
  • $\begingroup$ Yes, FADH2 is produced in step 6 and there doesn't seem any problem. But I still have problem with the fact that there isn't equal number of protons before reaction and after reaction in the picture I posted, and I don't feel your answer addressed this concern. $\endgroup$ – Kristaps Čivkulis May 26 at 22:23
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    $\begingroup$ So, as far as I understood, this extra H+ appeared from other reactions taking place in alpha-ketoglutarate dehydrogenase complex and which are not explicitly mentioned in the picture I posted? $\endgroup$ – Kristaps Čivkulis May 26 at 23:06

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