Haemoglobin binding sites

Gburek, J. Zabel, M. Osada, J. Immunohistochemical localization of haemoglobin binding sites in the distal tubule of the rat kidney. Histochem. J. 1998, 30, 421 24. 

There are two types of control shown by allosteric enzymes. They can be modulated by a molecule other than a substrate of the enzyme (termed heterotrophic enzymes, e.g. threonine dehydratase), or by the substrate itself (termed homotrophic enzymes, e.g. oxygen binding to haemoglobin). They contain two or more binding sites for the substrate, and activity is modulated by the number of binding sites which are filled. 

Haemoglobin A large protein with four binding sites for oxygen. It carries oxygen around the body for use by cells. It contains iron in its structure (haem). It also acts as a buffer to maintain a constant working pH of the blood. 

Fibrates should be used cautiously with warfarin and other coumarins, as the INR may rise significantly. The dose of anticoagulant should be reduced by 50% and then adjusted to INR or PT, using serial measurements [1, 28]. This is in addition to the effect of fibrates on haemoglobin, fibrinogen and antithrombin III, and the interaction may be related to displacement of warfarin from protein-binding site [28]. Fatalities have been reported. 

Homotropic this is where the sites are identical, and each sites is allosteric to the others. This is like the cooperative interactions seen in oxygen binding by haemoglobin - four (essentially) identical oxygen binding sites interacting with each other allosterically. 

Carbon monoxide binds to the iron atom in haemoglobin at the same binding site as oxygen, but it binds more avidly, indeed about 240 times more strongly. The product is carboxyhaemoglobin which may contain one or more carbon monoxide molecules. 

The competition between CO and oxygen for binding sites on haemoglobin was determined quantitatively by Bernard in 1963 and is represented by the following equation ... 

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