Chemical structures

Table of Contents

You really don't have to learn these! If you need to know a structure then you look it up. Sometimes it helps to know what kind of compound you are dealing with, and for people in that position, or those who are just plain curious I am collecting here the structures of some key compounds that were used to investigate mitochondrial metabolism.

Amino-oxyacetate: This hydroxylamine derivative reacts chemically with pyridoxal phosphate and blocks all transaminase reactions.

It inhibits the malate - aspartate cycle, and so can be used to estimate the flux through glutamate dehydrogenase without interference from the more active transamination pathway.

Antimycin A: This potent inhibitor of complex 3 acts between cytochrome b and cytochrome c1

Atractyloside: This toxic inhibitor of the adenine nucleotide porter is obtained from the mediterranean thistle, atractylis gummifera. It binds to the porter in the "outward facing" conformation, when it has just off-loaded its ATP into the cytosol and is about to bind an ADP for transport into the mitochondrial matrix space.

Bongkrekic acid: This toxic inhibitor of the adenine nucleotide porter is obtained from an unwelcome mould that sometimes grows on "bongkrek". This fermented Indonesian dish seems to be a hybrid between Danish blue cheese and rice pudding. The inhibitor binds to the porter in the "inward facing" conformation, when it has just delivered a fresh load of ADP into the mitochondrial matrix space. As a result, bongkrekate-inhibited mitochondria contain significantly more nucleotides than atractyloside-inhibited organelles. This can be used to estimate their molar content of adenine nucleotide porter proteins.

Cytochromes: All the cytochromes are heme proteins, but there are slight chemical differences between hemes a, b and c as a result of which their visible absorption bands are slightly displaced. Note that these compounds undergo chemical oxidation and reduction, cycling between ferrous and ferric forms, in contrast to hemoglobin where the iron is normally in the ferrous state. Cytochrome c (12 kd) is among the smallest of these molecules and functions in the intermembrane space as a mobile carrier of reducing equivalents between complex 3 and complex 4.

Heme a resembles heme b except that the starred methyl group is oxidised to a formyl group, and the starred vinyl group is replaced by a 17-carbon isoprenoid side chain, shorter but otherwise very similar to the branched hydrophobic side chain in Coenzyme Q.

Heme c is also similar to heme b, but in this case both of the heme vinyl groups react with cysteine residues in the protein, covalently attaching the heme residue to the polypeptide chain.

Flavins: The flavin derivatives FAD and FMN are synthesised from dietary riboflavin (vitamin B2). The are most commonly encountered as prosthetic groups, permanently attached to enzymes involved in redox reactions, where they function as temporary carriers of reducing equivalents as part of the catalytic mechanism.

FMN is very similar in properties to FAD, but lacking the AMP moiety it contains only flavin, ribitol (a sugar alcohol derived from ribose) and phosphate. Both coenzymes are bright yellow in the oxidised form, but become bleached on reduction.

Non-heme iron: This important class of proteins are very widely distributed in plants, animals and micro-organisms, where they are employed in a wide variety of redox reactions. There are hundreds of different types, which differ considerably in their structure and redox properties, but all contain one or more iron atoms surrounded by the sulphur - containing amino acid cysteine. For this reason they are often called "iron - sulfur" proteins.

Oligomycin: This compound inhibits ATP synthase (F0 / F1 ATPase) by binding to "oligomycin sensitivity confering peptide" (OSCP) in the stalk region of the enzyme.

Pyridine nucleotides: The pyridine nucleotide coenzymes NADH / NAD and NADPH / NADP are synthesised from nicotinamide (niacin, vitamin B3) and are the principal mobile carriers of reducing equivalents between soluble dehydrogenase enzymes and the respiratory chain.

The reduced forms of both coenzymes strongly absorb ultra-violet light around 340nm wavelength and a 0.1mM solution has an optical density of 0.62 in a 1cm light path length cuvette (extinction coefficient = 6220 litres/mole/cm). This forms the basis for numerous enzyme assay methods. In addition, if the reduced coenzymes are illuminated around 340nm they fluoresce strongly around 450nm and fractions of a nanomole are readily detected by this method. It is possible to monitor the oxidation and reduction of pyridine nucleotides in isolated mitochondria or even intact tissues using optical methods.

Rotenone: This potent inhibitor of mitochondrial complex 1 is a natural insecticide derived from derris root.

TTFA: This inhibitor of complex 2 is used in metallurgical processes.

Ubiquinol / ubiquinone: As its name suggests, this compound is very widely distributed in nature. There are species differences in the length of the isoprenoid side chain. All the natural forms are insoluble in water, but soluble in membrane lipids where they function as a mobile carrier of reducing equivalents between multi-enzyme complexes.

Home Page