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Cooperativity is a phenomenon displayed by systems involving identical or near-identical elements, which act non-independently of each other, relative to a hypothetical standard non-interacting system in which the individual elements are acting independently. One manifestation of this is enzymes or receptors that have multiple binding sites where the affinity of the binding sites for a ligand is ''apparently'' increased, positive cooperativity, or decreased, negative cooperativity, upon the binding of a ligand to a binding site. For example, when an oxygen atom binds to one of hemoglobin's four binding sites, the affinity to oxygen of the three remaining available binding sites increases; i.e. oxygen is more likely to bind to a hemoglobin bound to one oxygen than to an unbound hemoglobin. This is referred to as cooperative binding.〔Whitford, David: ''Proteins: structure and function'', 2005, John Wiley & Sons, pages 66-74〕 We also see cooperativity in large chain molecules made of many identical (or nearly identical) subunits (such as DNA, proteins, and phospholipids), when such molecules undergo phase transitions such as melting, unfolding or unwinding. This is referred to as subunit cooperativity. However, the definition of cooperativity based on apparent increase or decrease in affinity to successive ligand binding steps is problematic, as the concept of "energy" must always be defined relative to a standard state. When we say that the affinity is increased upon binding of one ligand, it is empirically unclear what we mean since a non-cooperative binding curve is required to rigorously define binding energy and hence also affinity. A much more general and useful definition of positive cooperativity is: A process involving multiple identical incremental steps, in which intermediate states are statistically ''underrepresented'' relative to a hypothetical standard system (null hypothesis) where the steps occur independently of each other. Likewise, a definition of negative cooperativity would be a process involving multiple identical incremental steps, in which the intermediate states are ''overrepresented'' relative to a hypothetical standard state in which individual steps occur independently. These latter definitions for positive and negative cooperativity easily encompass all processes which we humans call "cooperative", including conformational transitions in large molecules (such as proteins) and even psychological phenomena of large numbers of people (which can act independently of each other, or in a co-operative fashion). ==Cooperative binding== When a substrate binds to one enzymatic subunit, the rest of the subunits are stimulated and become active. Ligands can either have positive cooperativity, negative cooperativity, or non-cooperativity. An example of positive cooperativity is the binding of oxygen to hemoglobin. One oxygen molecule can bind to the ferrous iron of a heme molecule in each of the four chains of a hemoglobin molecule. Deoxy-hemoglobin has a relatively low affinity for oxygen, but when one molecule binds to a single heme, the oxygen affinity increases, allowing the second molecule to bind more easily, and the third and fourth even more easily. The oxygen affinity of 3-oxy-hemoglobin is ~300 times greater than that of deoxy-hemoglobin. This behavior leads the affinity curve of hemoglobin to be sigmoidal, rather than hyperbolic as with the monomeric myoglobin. By the same process, the ability for hemoglobin to lose oxygen increases as fewer oxygen molecules are bound.〔 ''See also Oxygen-hemoglobin dissociation curve. Negative cooperativity means that the opposite will be true; as ligands bind to the protein, the protein's affinity for the ligand will decrease, i.e. it becomes less likely for the ligand to bind to the protein. An example of this occurring is the relationship between glyceraldehyde-3-phosphate and the enzyme glyceraldehyde-3-phosphate dehydrogenase. Homotropic cooperativity refers to the fact that the molecule causing the cooperativity is the one that will be affected by it. Heterotropic cooperativity is where a third party substance causes the change in affinity. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Cooperativity」の詳細全文を読む スポンサード リンク
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