Molecular interactions in cells Many Metabolic pathways biochemical

Molecular interactions in cells Many Metabolic pathways (biochemical pathways) Complex often series of enzyme controlled reactions Energy transformed Molecules degraded and synthesised

ATP - Adenosine Triphosphate nucleic acid – adenine base, ribose sugar, three phosphate groups stores energy and makes it available energy is used for chemical, transport and mechanical work

Catalysis Metabolism of an organism is the series of complex biochemical reactions that occur within them. Reactions are sped up (catalysed) by enzymes.

Anabolic Reactions • Uses energy to SYNTHESISE large molecules from smaller ones e. g. Amino Acids Proteins • Also known as endothermic reactions ENDOTHERMIC REACTION

Catabolic Reactions • These release energy through the BREAKDOWN of large molecules into smaller units e. g. Cellular Respiration: ATP ADP + Pi • Also known as exothermic reactions EXOTHERMIC REACTION

Enzyme characteristics made of protein catalyse reactions affected by temperature and p. H denatured at high temperature are specific to a reaction because of their active site.

Enzymes All chemical reactions require energy to enable them this is the activation energy. Enzymes lower the activation energy. 2 types of reaction are: Anabolic (synthesis) a dehydration synthesis reaction. Catabolic (degradation) a hydrolysis reaction.

Enzyme types Proteases - break down proteins into amino acids by breaking peptide bonds (hydrolysis). Nucleases - break down nucleic acids into nucleotides (hydrolysis). Kinases - add phosphate groups to molecule. Phosphatases – remove phosphate groups ATPases - hydrolysis of ATP.

Enzyme activity Active site is region where the reaction with substrate occurs. Correct substrate alters the shape of the active sight to allow the substrate to fit perfectly. This is called the 'induced fit model'. (Molecules close to shape of substrate may react with differing efficiencies)

Control of Enzyme activity Control of enzyme activity occurs in these ways number of enzyme molecules present compartmentalisation change of enzyme shape by competitive inhibitors, non-competitive inhibitors, enzyme modulators, covalent modification end product inhibition

Competitive inhibition A molecule close to shape of substrate competes directly for active site so reducing the concentration of available enzyme. This can be reversed by increasing the concentration of the correct substrate unless the binding of competitor is irreversible.

Malonate example Succinate dehydrogenase catalyses the oxidation of succinate to fumarate (respiration) Malonate is the competitive inhibitor

Non-competitive inhibition An inhibitor binds to the enzyme molecule at a different area and changes the shape of the enzyme including the active site. This may be a permanent alteration or may not.

• Inhibition can either be reversible or non-reversible • Some inhibitors bind irreversibly with the enzyme molecules. • The enzymatic reactions will stop sooner or later and are not affected by an increase in substrate concentration. • These are irreversible inhibitors heavy metal ions including silver, mercury and lead ions.

Enzyme modulators Some enzymes change their shape in response to a regulating molecule. These are called allosteric enzymes Positive modulators (activators) stabilise enzyme in the active form. Negative modulators (inhibitors) stabilise enzyme in the inactive form.

Allosteric Enzymes

Covalent modifications Involves the addition, modification or removal of a variety of chemical groups to or from an enzyme (often phosphate. ) These result in a change in the shape of the enzyme and so its activity. These include phosphorylation by kinases and dephosphorylation by phosphatases. Conversion of inactive forms to active forms e. g. trypsinogen and trypsin

An example of activation is trypsinogen to trypsinogen activated by enterokinase in duodenum

Trypsin is synthesised in the pancreas, but not in its active form as it would digest the pancreatic tissue • Therefore it is synthesised as a slightly longer protein called TRYPSINOGEN • Activation occurs when trypsinogen is cleaved by a protease in the duodenum • Once active, trypsin can activate more trypsinogen molecule

An example of phosphorylation activating an enzyme is the skeletal muscle enzyme GLYCOGEN PHOSPHORYLASE Glycogen is converted to glucose when heavy demands are placed on muscle tissue Glycogen phosphorylase must be activated when sugar is needed and quickly deactivated when glucose is plentiful.

Glucose and ATP act as negative modulators AMP (adenosine monophosphate) acts as a positive modulator This is useful, because AMP is a product of ATP breakdown and will be more plentiful when energy levels are low and more glucose is needed A further complication is that there is a hormonal control mechanism by adrenaline and glucagon

End product Inhibition Often seen in pathways that involve a series of enzyme controlled reactions. The end product once produced has an inhibiting affect on an enzyme in the reaction. Example: Bacterial production of amino acid isoleucine from threonine. 5 stages enzyme controlled Threonine Isoleucine

End-Product Inhibition Metabolism is organised as a series of metabolic pathways, and control of these pathways is an important feature of cell biochemistry End-product inhibition is energetically efficient as it avoids the excessive (and wasteful) production of the intermediates of a pathway This is a form of NEGATIVE FEEDBACK

describe the catalytic functions of proteases, nucleases, ATPases and kinases describe the induced fit model of enzyme activity explain how competitive and non-competitve inhibitors affect enzyme activity describe allosteric enzymes explain the effect of positive and negative modulators binding to allosteric enzymes explain what is meant by covalent modification of enzymes and how they control enzyme activity explain the role of end-product inhibition in the control of metabolic pathways