(a) Explain enzymes, their characteristics as well as induced-fit model of mechanism of enzyme action. (20 marks) (b) List…

(a) Enzymes, their characteristics and the induced-fit model

Enzymes are biological catalysts, mostly proteins (a few are RNA, called ribozymes), which speed up chemical reactions in cells by lowering the activation energy, without being used up. Characteristics: They are highly efficient: the rate of a reaction may rise by a factor of 10⁶ to 10¹², and a small amount of enzyme acts on much substrate. They are specific for their substrate or type of reaction, because of the shape and chemistry of the active site. They are not changed by the reaction, and they do not alter the equilibrium, only the speed at which it is reached. Their action depends on temperature (optimum about 37°C for human enzymes), pH, substrate concentration and enzyme concentration. High heat denatures them. They are regulated by inhibitors, activators and allosteric modulators, and often need a cofactor or coenzyme. They are grouped by the IUBMB into seven classes: oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases and translocases. Induced-fit model: Fischer's lock-and-key model treated the active site as a rigid, ready-made mould. Koshland (1958) proposed that the active site is flexible, and that the binding of the substrate induces a change in its shape. Step 1: The substrate binds to the active site by weak bonds. Step 2: The enzyme changes shape and brings its catalytic groups into the best position, straining the substrate bonds and stabilising the transition state. Step 3: The products form and leave, and the enzyme returns to its original shape. It explains why some enzymes act on a range of related substrates and how allosteric and competitive effects arise.

(b) Coagulation factors and their role in blood clotting

List of coagulation factors: Factor I: fibrinogen. Factor II: prothrombin. Factor III: tissue factor (thromboplastin). Factor IV: calcium ions. Factor V: proaccelerin. Factor VII: proconvertin. Factor VIII: antihaemophilic factor. Factor IX: Christmas factor. Factor X: Stuart-Prower factor. Factor XI: plasma thromboplastin antecedent. Factor XII: Hageman factor. Factor XIII: fibrin-stabilising factor. Factor VI is not now recognised, being the same as activated factor V. Factors II, VII, IX and X need vitamin K for their formation. Role in clotting: Extrinsic pathway: injured tissue releases factor III, which with factor VII and calcium activates factor X. Intrinsic pathway: contact of blood with collagen activates factor XII, which activates XI and then IX. Factor IXa with factor VIII, platelet phospholipid and calcium activates factor X. Common pathway: Xa with factor V, phospholipid and calcium forms the prothrombin activator, which converts prothrombin (II) into thrombin. Thrombin splits fibrinogen into fibrin, which forms a net. Factor XIII, activated by thrombin and calcium, cross-links the fibrin so that the clot is firm. Deficiency of factor VIII or IX causes haemophilia A or B.

(c) Neoteny and how it differs from paedogenesis

Neoteny is the retention of larval or juvenile features by an animal that is sexually mature, because the development of the body is retarded while the gonads mature at the normal time. Example: the axolotl, Ambystoma mexicanum, keeps external gills, tail fin and aquatic life as an adult and breeds as a larva, because its metamorphosis fails due to low thyroid hormone. Its metamorphosis can be induced by thyroxine. Necturus and Proteus are other examples. It is considered important in the origin of chordates and in human evolution. Difference between neoteny and paedogenesis: Mechanism: in neoteny the growth and development of the body are slowed down. In paedogenesis the gonads mature early, so the larva reproduces while the body develops at the normal rate. Stage: a neotenic animal is an adult in time but larval in form, and a paedogenic animal is a larva that reproduces. Mode: neoteny occurs in amphibians. Paedogenesis is found in some insects, such as the gall midge Miastor, and in the larval stages of liver flukes. Reproduction: a neotenic form reproduces sexually. A paedogenetic larva often reproduces by parthenogenesis. Both lead to paedomorphosis.