词条 | EC50 |
释义 | EC50,半最大效应浓度(concentration for 50% of maximal effect,EC50)是指能引起50%最大效应的浓度。 EC50是药物安全性指标。 其含义是:引起50%个体有效的剂量。 LD50/ED50、TD50/ED50、TC50/EC50等统称为治疗指数,是一类药物的安全指标,通常其值越大越安全。需注意这些指标只反映治疗作用与急性毒性的关系,并不能反映慢性毒性、过敏性。In biochemistry, the binding of a ligandto a macromoleculeis often enhanced if there are already other ligands present on the same macromolecule (this is known as Cooperative binding). The Hill coefficient, named for Archibald Vivian Hill, provides a way to quantify this effect. It describes the fraction of the macromolecule saturated by ligandas a function of the ligand concentration; it is used in determining the degree of cooperativeness of the ligand binding to the enzyme or receptor. It was originally formulated by Archibald Hillin 1910 to describe the sigmoidal O2binding curve of hemoglobin. A coefficient of 1 indicates completely independent binding, regardless of how many additional ligands are already bound. Numbers greater than one indicate positive cooperativity, while numbers less than one indicate negative cooperativity. The Hill coefficient was originally devised to explain the cooperative binding of oxygen to Hemoglobin(a system which has a Hill coefficient of 2.8-3). Hill equation: θ- fraction of occupied sites where the ligandcan bind to the active site of the receptor protein. [L]- free (unbound) ligandconcentration Kd- Apparent dissociation constantderived from the law of mass action(equilibrium constant for dissociation) KA- ligand concentration producing half occupation (ligand concentration occupying half of the binding sites), that is also the microscopic dissociation constant. n- Hill coefficient, describing cooperativity (or possibly other biochemical properties, depending on the context in which the Hill equation is being used) Taking the reciprocal of both sides, rearranging, inverting again, and then taking the logarithm on both sides of the equation leads to an alternative formulation of the Hill equation: When appropriate, the value of the Hill coefficient describes the cooperativity of ligand binding in the following way: n> 1- Positively cooperative reaction: Once one ligand molecule is bound to the enzyme, its affinity for other ligand molecules increases. n< 1- Negatively cooperative reaction: Once one ligand molecule is bound to the enzyme, its affinity for other ligand molecules decreases. n= 1-Noncooperative reaction: The affinity of the enzyme for a ligand molecule is not dependent on whether or not other ligand molecules are already bound. The Hill equation (as a relationship between the concentration of a compound adsorbing to binding sites and the fractional occupancy of the binding sites) is equivalent to the Langmuir equation. With the Hill eqiaton, we can derive that EC50=KA. |
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