Classify the cytochromes and describe their role in biological oxidation.

Definition

• They are one-electron carriers, unlike NAD and FAD which carry two
• The name means "cellular pigment" — they have characteristic absorption spectra, which is how they were discovered

Classification

Cytochrome C — Special Features

• Small (104 amino acids) and water-soluble
• Loosely attached to the outer surface of the inner membrane, so it shuttles between complexes III and IV
• Highly conserved through evolution — widely used in phylogenetic studies
• Release into the cytosol triggers apoptosis by activating Apaf-1 and caspase-9 — a second, entirely separate function

Cytochrome Oxidase (complex IV)

• Contains cytochromes a and a3 plus two copper centres (CuA and CuB)
• The only cytochrome that reacts directly with oxygen
• Catalyses: 4 cyt c (Fe2+) + O2 + 4H+ → 4 cyt c (Fe3+) + 2H2O
• Reduces oxygen completely to water in one step, holding the intermediates bound so no free radicals escape — a critical safety feature
• Inhibited by cyanide, carbon monoxide, azide and hydrogen sulphide, all binding cytochrome a3
• Copper deficiency impairs it — part of the anaemia and neurological features of Menkes disease

Comparison of Electron Carriers

Applied Aspects

• Cyanide poisoning — binds cytochrome a3; histotoxic hypoxia with bright red venous blood and a high venous oxygen saturation, since tissues cannot extract oxygen
• Cytochrome c release is a central event in apoptosis, and is exploited by many anticancer drugs
• Cytochrome P450 polymorphisms determine individual responses to drugs — codeine, warfarin, clopidogrel
• Iron deficiency reduces cytochrome synthesis, contributing to the fatigue and reduced exercise capacity that precede anaemia
• Mitochondrial DNA encodes several cytochrome subunits, which is why mitochondrial mutations impair the chain and are maternally inherited