Chp 2 Molecules and Cells in Animal Physiology Read Chp 2 of the book Use the notes for Human Physiology We will see metabolism and the enzymes in more details

Metabolism Set of processes by which the cells or organisms acquire, rearrange, and void compounds in ways that sustain life. Catabolism: Set of processes by which complex chemical compounds are broken down to release energy, create smaller molecules or prepare a compound for elimination Anabolism: Sets of processes that synthesize larger or more complex chemicals from smaller compounds, using energy.

Enzymes Protein catalysts: 1) speed chemical reactions and 2) regulate reactions Reactions are characteristic of enzymes Enzymes have substrate(s) and product(s)

Enzymes as catalysts The enzyme needs to bind to its substrate Then, the enzyme proceeds with its reaction, forming a product. It then releases the product, and binds the next round of substrate E + S  E-S complex  E-P complex  E + P Reaction velocity: amount of substrate converted to product per unit of time However, the velocity varies during the reaction

Enzyme kinetics If one looks at the appearance of the product: 1- slow appearance as only a few of the enzymes are actually working 2- faster: most of the enzymes are bound and working 3- all of the enzymes are bound and working- saturation of enzymes  maximum velocity Vmax This curve is well known and useful

Enzyme kinetic Maximum reaction velocity, Vmax = depend on catalytic effectiveness of enzyme, Kcat. Depends on the level of activation energy needed to allow the reaction and on the conformational changes of the enzymes

Enzyme kinetic An enzyme that is unlikely to form a complex with a compound has a low affinity for the compound An enzyme that readily binds a substrate and transforms it, has a high affinity for the substrate The Michaelis constant, Km, is the amount of substrate needed to reach half Vmax. The higher the affinity, the smaller Km. In cells, the concentrations of substrate are often subsaturating. Therefore, the reaction velocities will depend on these 3 factors: 1- the number of active enzyme molecules 2- the catalytic effectiveness of the enzymes, when saturated (Vmax) 3- the affinity of the enzyme for the substrate (Km)

Enzyme properties Ligand: a compound that binds selectively and non-covalently to a site When an enzyme has several binding sites: Positive cooperativity: binding of a substrate is facilitated if another substrate is already bound Negative cooperativity: the opposite of above Examples?

Enzyme properties Allosteric modulation if the enzyme has several sub-units. The binding of a non- substrate molecule allosteric modulator) can affect the binding to the substrate  allosteric activation or inhibition Important mean of regulating an enzyme

Enzyme properties Enzymes catalyze a reaction in both direction. However, one direction is usually favored Many forms of an enzyme can exist within a cell, organism or population  isozymes Isozymes vary in Vmax and Km, and are usually adapted to specific conditions Examples?

Enzymes and Cell functions Regulated by enzymes - Constitutive enzymes: always there in constant amount, regardless of conditions - Inducible enzymes: amounts vary with conditions Modulation of existing enzymes permits fast regulation of cell function  up and down regulation Feedback inhibition: an end product can modify the activity of an upstream enzyme

Enzymes in cells Covalent modulation of existing enzymes: a covalent bond between an enzyme and its modulator is broken Ex: phosphorylation and dephosphorylation Requires the action of enzymes, protein kinases and phosphatases, to modify these covalent bonds Reaction is amplified

Evolution of enzymes The ability to decipher the protein and/or DNA sequence allows to study the evolutionary relationship between the proteins. The relationships are deducted from the mutations

Evolutionary relationships The allelic frequencies follow a geographic range. The allelic forms (isozymes) are adapted to the local conditions. In this case, it is temperature.

Cell signaling Read this paragraph. (mostly cell biology) Any protein involved in these process are subject to mutation and adaptation through natural selection