Coenzyme Q is part of the electron transport process. 

[CoQ10 was considered a cofactor and not a vitamin but may be things are different now.  ;) ]

Sidharta,

Ubiquinone-cytochrome c oxidoreductase (also known as Complex III and cytochrome c reductase) is one of the proton pumps in the respiratory chain, whose function is to catalyze the transfer of electrons from ubiquinol to oxidized cytochrome c, a water-soluble protein, and concomitantly pump protons out of the mitochondrial matrix; ubiquinol is a co-substrate here, and is oxidized to ubiquinone (CoQ10) during catalysis by the enzyme.   

Thanks for your answer Dr. Kandaswami.

I also found that flavin/FAD can undergo one electron reduction to form a semiquinone radical which forms a part of cytochrome C oxidoreductase enzyme complex. FADs can exist in different redox states, including quinone and semiquinone. Favins can also undergo 2 electron reduction to form dihydroflavin, and hence is an intermediate involving nicotinamide nucleotides. This provides some direct evidence that flavoproteins forms the prosthetic group of FAD which act as coenzymes, and riboflavin as a central component of the redox cofactor FAD/FMN. Since quinones serve as electron acceptors in aerobic respiration (as you have mentioned), it is indeed a part of cytochrome C reductase which require vitamin riboflavin.

Regards, Sidharta

Dear Sidharta,

Flavins form the prosthetic groups of flavoproteins. The flavin derivative, FAD (flavin adenine dinucleotide), functions as a coenzyme; it constitutes the prosthetic group of several flavoproteins.  Enzymes that utilize flavin coenzymes are known as flavoproteins, which comprise dehydrogenases, oxidases and oxygenases.  FMN and FAD, coenzymes of flavin enzymes, are synthesized from their precursor, (the B vitamin) riboflavin, which is well absorbed through the intestine in animal tissues. FMN (flavin mononucleotide, which is riboflavin 5’-phosphate) is not a nucleotide.

Reactivity of Flavins” (K. Yagi, ed.). Tokyo: University Press, 1975. Yagi, K., ed.: Flavins and Flavoproteins. Tokyo: University of Tokyo Press. 1968.

The prosthetic group of NADH-Q oxidoreductase is FMN (Q is coenzyme Q, also termed CoQ, Q or ubiquinone) while the prosthetic group of succinate-Q oxidoreductase (succinate:ubiquinone oxidoreductase or succinate dehydrogenase) is FAD (and Fe-S). Q-cytochrome c oxidoreductase (complex III, also known as  CoQ cytochrome reductase) and cytochrome c oxidase do not contain flavin derivatives as prosthetic groups.  Riboflavin is not required as a precursor for Q-cytochrome c oxidoreductase. 

Thanks Dr.Kandaswami for your excellent explanation. Your explanations are very helpful.

According to what you have mentioned, riboflavin is not required as a precursor for Q-cytochrome c oxidoreductase, but I find this confusing, since some textbooks mention that riboflavin is an essential component required for the assembly of cytochrome c oxidoreductase, while others hold the view that riboflavin is required for synthesis and functioning of cytochrome c oxidoreductase. Yes, riboflavin is the central component of cofactor FAD and FMN where they function as flavoproteins in Complex I & II.

I found an article on MRC disorder1 which however, says that riboflavin "enhances" the assembly of mitochondrial cytochrome c oxidoreductase (that of NADH-ubiquinone oxidoreductase or, Complex I), and that which increases its catalytic activity (as you have mentioned earlier, quite related to this article which mentions about Complex I & IV). So riboflavin actually promotes the assembly of both these complexes. Anyway, I just need to know what are the vitamins required for assembly and functioning of cytochrome-c-oxidoreductase complex III. Is riboflavin required in Complex III functioning?

Dr. Kandaswami if you can shed some of your knowledge on this related question it would be much helpful.

What are the essential components required for the synthesis of the cofactors of enzyme coenzyme Q : cytochrome c — oxidoreductase? Do they require any Vitamins?

1http://www.sciencedirect.com/science/article/pii/S0005272805002744

Best Regards, Sidharta

Sidharta,

I shall gladly attempt to provide some explanations, as you had asked. I am going to subdivide the answers in order to minimize any confusion that may arise.

There appears to be a terminology issue. What you have referred to as "cytochrome reductase" is NADH:ubiquinone oxidoreductase (complex I) or NADH: cytochrome c reductase (see Mahler et al [1952] below) of the mammalian respiratory chains (wherein the confusion lies). It is a flavoprotein (a protein using a flavin component). Riboflavin mainly occurs in the body as integral parts of the coenzymes, FAD and FMN. In the body, riboflavin is primarily found as an integral component of the coenzymes, flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), also termed as flavocoenzymes in view of their origin from riboflavin.  NADH:ubiquinone oxidoreductase (complex I) contains FMN as a prosthetic group;  it is a component of complex I of the mammalian mitochondrial electron transport system;  the enzyme has also been called as "reduced nicotinamide adenine dinucleotide (NADH) dehydrogenase or (NADH dehydrogenase)" or NADH:cytochrome c reductase. In 1952, Mahler et al reported on the purification and characterization of this enzyme. The previous nomenclature for this enzyme was "diphosphopyridine nucleotide-cytochrome c reductase"; the coenzyme, NADH, was earlier called DPNH  (reduced diphosphopyridine nucleotide).

MAHLER HR, SARKAR NK, VERNON LP. Studies on diphosphopyridine

nucleotide-cytochrome c reductase. II. Purification and properties. J Biol Chem.

1952 Dec;199(2):585-97. PubMed PMID: 13022665.   

http://www.jbc.org/content/199/2/585.long

The NADH:ubiquinone oxidoreductase (complex I) of respiratory

chains. J. E. Walker, Q Rev Biophys. 1992 Aug;25(3):253-324. Review. PubMed PMID: 1470679. 

Dear Sidharta,

What I had posted: >> Q-cytochrome c oxidoreductase (ubiquinol:cytochrome c oxidoreductase) is complex III. To reiterate, It is not NADH-Q oxidoreductase, which is complex I (also known as NADH:ubiquinone oxidoreductase, which integrally contains FMN as a prosthetic group; it is a component of complex I of the mammalian mitochondrial electron transport system); the enzyme has been variably called as "reduced nicotinamide adenine dinucleotide (NADH) dehydrogenase or "NADH dehydrogenase" or "NADH:cytochrome c reductase."  Q-cytochrome c oxidoreductase (ubiquinol:cytochrome c oxidoreductase, which is complex III) is not an NADH enzyme.

" There should be is no confusion here; what you are calling cytochrome c oxidoreductase is the enzyme that has also been called as "reduced nicotinamide adenine dinucleotide (NADH) dehydrogenase or "NADH dehydrogenase" or NADH:cytochrome c reductase or NADH:ubiquinone oxidoreductase complex I of mammalian respiratory chains, which contains a riboflavin derived coenzyme.

MAHLER HR, SARKAR NK, VERNON LP. Studies on diphosphopyridine

nucleotide-cytochrome c reductase. II. Purification and properties. J Biol Chem.

1952 Dec;199(2):585-97. PubMed PMID: 13022665.   

http://www.jbc.org/content/199/2/585.long

The NADH:ubiquinone oxidoreductase (complex I) of respiratory

chains. J. E. Walker, Q Rev Biophys. 1992 Aug;25(3):253-324. Review. PubMed PMID: 1470679. 

Grad LI, Lemire BD. Mitochondrial complex I mutations in Caenorhabditis elegans produce cytochrome c oxidase deficiency, oxidative stress and vitamin-responsive lactic acidosis. Hum Mol Genet 2004; 13: 303–314.

Dear Sidharta,

You wrote: Yes, it may but this study examines certain mutants of Caenorhabditis elegans. Here are the earlier papers on this. We are talking about complex IV of C. elegans. 

Grad LI, Lemire BD. Riboflavin enhances the assembly of mitochondrial cytochrome c oxidase in C. elegans NADH-ubiquinone oxidoreductase mutants. Biochim Biophys Acta 2006; 1757: 115–122.

 1http://www.sciencedirect.com/science/article/pii/S0005272805002744

Mitochondrial complex I mutations in Caenorhabditis elegans produce cytochrome c oxidase deficiency, oxidative stress and vitamin-responsive lactic acidosis.  http://hmg.oxfordjournals.org/content/13/3/303.full.   Intriguingly, the mutants of Caenorhabditis elegans, exhibit notable decrements in the quantities and activities of complex I and complex IV. Riboflavin supplementation promoted the assembly and activity of these complexes. Promoting complex I assembly with riboflavin led to the added benefit of partially reversing complex IV deficit. Some deficiencies in certain mutants of C. elegans could be corrected, in part,  with the vitamins, riboflavin and thiamine, or with sodium dichloroacetate, an activator of the pyruvate dehydrogenase complex.

Dear Sidharta,

You wrote: Obviously, what I wrote was about Q-cytochrome c oxidoreductase, which constitutes complex III of mammalian mitochondrial respiratory chain (it is not an NADH enzyme), and not about NADH-ubiquinone oxidoreductase or, complex I.  

You wrote > You have mentioned mitochondrial cytochrome c oxidoreductase and  NADH-ubiquinone oxidoreductase or complex I in the same sentence. However, when you were reading what I wrote about the non-requirement of riboflavin for Q-cytochrome c oxidoreductase (complex III) you perhaps thought that I was talking about mitochondrial cytochrome c oxidoreductase (NADH-ubiquinone oxidoreductase or, complex I). This could have caused confusion.

I trust that the picture now is clear. It is unfortunate that my answer is too very lengthy and clumsy.

Dear Sidharta,

Per your request, here are some details concerning prosthetic groups of enzymes of the mammalian mitochondrial respiratory chain.

1.   NADH:ubiquinone oxidoreductase (complex I; prosthetic groups, FMN and Fe-S).

2.  Succinate:ubiquinone oxidoreductase (complex II; prosthetic groups, FAD and Fe-S).   

3. Ubiquinol:cytochrome c oxidoreductase (complex III; succinate dehydrogenase; prosthetic groups, different heme components and Fe-S). 

4. Ferrocytochrome c:oxygen oxidoreductase (complex IV; cytochrome c oxidase; prosthetic groups, different hemes and Cu).

5. ATP synthase (complex V).

Complex II is the only membrane-bound component of the Krebs cycle. It also functions as a member of the electron transport chain in the mitochondrion. Complex II is the flavoprotein, succinate dehydrogenase (succinate:CoQ oxidoreductase).  Fe-S clusters in iron-sulfur proteins (also called nonheme iron proteins), which play critical roles in a wide range of reduction reactions in biological systems.

The Mitochondrial Electron Transport and Oxidative Phosphorylation System. Annual Review of Biochemistry Vol. 54: 1015-1069 (Volume publication date July 1985) DOI: 10.1146/annurev.bi.54.070185.005055.  Y. Hatefi

Dear Dr. Kandaswami,

I must thank you for your excellent clarification and detailed explanations which helped clear a lot of confusion regarding the nomenclature, functions, and components of the enzymes of the respiratory chain, and particularly, about cytochrome c reductase.

It is now clear that what I "have been calling cytochrome c oxidoreductase is the enzyme that has also been called as "reduced nicotinamide adenine dinucleotide (NADH) dehydrogenase or "NADH dehydrogenase", and this clears the confusion right away.

Particularly your classification in the above article / post is an easy-way guide to conceptualize the enzyme complexes of the mitochondrial respiratory chain.

Thank you again for your time and expertise.

Best Regards, Sidharta

Dear Sidharta,

Thank you!

Since the complex I enzyme has been variously called in publications and books anybody would be confused. Confusion is confounded when some papers use a short name, a sort of trivial name. such as cytochrome c reductase. I shall get back to you about another aspect that you had touched upon (FADH2 or something related).

Best regards...