Biomaterial Database

The catalytic mechanism of carbonic anhydrase. 1973

S Lindskog, and J E Coleman

It is shown that an "inverse" relationship between the pH dependencies of the rates of hydration of CO(2) and dehydration of HCO(3) (-) by carbonic anhydrase (EC 4.2.1.1) is a direct consequence of the thermodynamic equilibrium between CO(2) and HCO(3) (-) and independent of any assumptions about the catalytic mechanism. It is further shown that proposed mechanisms for carbonic anhydrase involving HCO(3) (-) as the substrate in the dehydration reaction and a proton transfer reaction, EH(+) right harpoon over left harpoon E + H(+), as an obligatory step during catalysis obey the rule of microscopic reversibility. This includes mechanisms in which the proton dissociation is from a zinc-coordinated water molecule. Such mechanisms can be in accord with the observed rapid turnover rates of the enzyme, since rapid proton exchange can occur with the buffer components, EH(+) + B right harpoon over left harpoon E + BH(+). Mechanisms in which H(2)CO(3) is the substrate in dehydration avoid the proton-transfer step, but require that H(2)CO(3) combines with enzyme more rapidly than in a diffusion-controlled reaction. Physico-chemical evidence for and against a zinc-hydroxide mechanism is discussed.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008024	Ligands	A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)	Ligand
D002245	Carbon Dioxide	A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals.	Carbonic Anhydride,Anhydride, Carbonic,Dioxide, Carbon
D002256	Carbonic Anhydrases	A family of zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide. They play an important role in the transport of CARBON DIOXIDE from the tissues to the LUNG. EC 4.2.1.1.	Carbonate Dehydratase,Carbonic Anhydrase,Anhydrases, Carbonic,Dehydratase, Carbonate
D002384	Catalysis	The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.	Catalyses
D004579	Electron Transport	The process by which ELECTRONS are transported from a reduced substrate to molecular OXYGEN. (From Bennington, Saunders Dictionary and Encyclopedia of Laboratory Medicine and Technology, 1984, p270)	Respiratory Chain,Chain, Respiratory,Chains, Respiratory,Respiratory Chains,Transport, Electron
D006863	Hydrogen-Ion Concentration	The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH	pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D001639	Bicarbonates	Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the pH of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity.	Bicarbonate,Bicarbonate Ions,Hydrogen Carbonates,Bicarbonate Ion,Carbonic Acid Ions,Hydrogen Carbonate,Carbonate, Hydrogen,Carbonates, Hydrogen,Ion, Bicarbonate,Ions, Bicarbonate,Ions, Carbonic Acid
D015032	Zinc	A metallic element of atomic number 30 and atomic weight 65.38. It is a necessary trace element in the diet, forming an essential part of many enzymes, and playing an important role in protein synthesis and in cell division. Zinc deficiency is associated with ANEMIA, short stature, HYPOGONADISM, impaired WOUND HEALING, and geophagia. It is known by the symbol Zn.