Section 6 – Metabolism & Enzymes Unit 1 – Human Cells

Cell Metabolism The sum of all the biochemical reactions that occur in a living cell - most of these are connected within a complex network - most reactions are catalysed by enzymes Metabolic Pathways: 2 types Catabolic: - the breakdown of complex molecules into simpler ones - involves the release of energy Anabolic: - the biosynthesis of complex molecules from simpler ones - requires the input of energy These two pathways often depend on one another

Two types of pathway Aerobic respiration is a type of catabolic pathway - releases energy (ATP) This energy can then be used for the synthesis of protein from amino acids - an anabolic pathway - requires energy

Reversible and Irreversible steps Metabolic pathways have both reversible and irreversible stages Glycolysis converts glucose to pyruvic acid - involves many intermediates along the way Glucose is converted to intermediate 1 by enzyme 1 - this is irreversible Ensures levels of glucose stay low within a cell - allows more glucose to diffuse into the cell Intermediate 1 converting to intermediate 2 is reversible - aided by enzyme 2 - if the cell has an excess of intermediate 2, it can be reversed to intermediate 1 - this can then be used in an alternative pathway Intermediate 2, to intermediate 3 is irreversible - glycolysis MUST continue

Alternative Routes Allow for steps in a pathway to be bypassed In glycolysis, glucose can be converted into sorbitol - this bypasses 3 intermediates, and rejoins the pathway at a later stage Used when there is a plentiful supply of sugar

Activation energy & enzyme action Chemical reactions require chemical bonds to be broken in the reactants The energy needed to break these bonds is the activation energy Bonds break when reactants absorb energy to make them unstable - now in a transition state - reaction can proceed Energy input is often in the form of heat

Properties & Functions of a catalyst Catalysts: - lower the activation energy for a chemical reaction - speed up the rate of a chemical reaction - take part in the reaction, but remain unchanged Living cells can’t withstand high temperatures - require a catalyst to help reactions proceed at low temperatures Biological catalysts are called enzymes Biochemical reactions couldn’t proceed without enzymes

Enzyme action Enzymes are made of protein On their surface they have an active site The shape of this site is determined by the chemical structure and bonding of amino acids within the polypeptide chains Enzymes are specific - only act on one substrate Chemical structure of substrate complements the active site - shows an affinity (chemical attraction)

Induced fit and orientation The active site is flexible and dynamic It’s shape changes slightly to incorporate the substrate - an induced fit If 2 substrates are involved, the active site determines their orientation The active site weakens chemical bonds in the substrates - lowering the activation energy Once complete, products have a low affinity for the active site - products separate

Direction of enzyme action Metabolic pathways involve many reactions - each involving an enzyme E.g. enzyme 2 only works when substrate B is available - a product of one reaction (intermediate metabolite) is the substrate for the next Most metabolic pathways are reversible Enzymes can go into reverse, and convert intermediates back E.g. If C was in excess, enzyme 2 could convert it back to B Enzymes often form part of a multi-enzyme complex

Factors affecting enzyme action Enzymes require a suitable temperature, pH and a supply of substrate to be able to function Substrate concentration: At low concentrations, the reaction rate is low - too few substrates to fill the active sites Increasing concentration, more active sites filled - increasing rate of reaction Eventually all active sites are filled (saturation) - reaction rate levels off

Control of metabolic pathways Metabolic pathways involve several stages Involve metabolites (intermediates) being converted by an enzyme Each enzyme is coded for by a gene (or genes) If an enzyme is absent, the pathways stop Therefore, gene expression can regulate enzyme action

Enzyme control – switching genes on/off Some metabolic pathways are only required to operate at certain times Enzymes are therefore only produced when needed - helps conserve cell resources - e.g. ATP, amino acids Genes for producing enzymes can therefore be switched “on” or “off” when required - enzyme induction E.g. In E.Coli, enzymes only active if lactose is present

Gene action in E.coli E.coli can only obtain glucose by breaking down lactose Lactose is digested by the enzyme B-galactosidase The enzyme is only produced when lactose is present This is gene expression being regulated by a signal molecule

Lac Operon – absence of lactose An operon consists of: structural genes - contain the DNA code for an enzyme operator gene - which controls the structural gene The operator gene is switched off by a repressor molecule - this is coded for by a regulator gene

Lac operon – presence of lactose If lactose is present, it binds to the repressor Therefore the operator gene is now free The structural gene switches on - B-galactosidase production starts Once all lactose has been digested, the repressor is freed It binds again to the operator gene – no more enzyme

Control by regulation of enzyme action Signal molecules: e.g. Epinephrine – a hormone released by the adrenal glands - binds to membrane receptors on liver cells - activates the cells to produce an enzyme - this converts glycogen stores into glucose Signal molecules can be intracellular or extracellular

Control by regulation of enzyme action Inhibitors: - a substance that can decrease the rate of an enzyme controlled reaction COMPETITIVE - compete with the substrate for the enzyme’s active site - has a structure similar to the substrate - as active sites get blocked, reaction rate decreases - increasing substrate concentration can help reaction rate to increase again - substrates outnumber the inhibitor

Control by regulation of enzyme action Inhibitors: NON-COMPETITIVE - don’t combine with the enzyme’s active site - attach to a non-active (allosteric) site - this changes the overall enzyme shape - active site is therefore affected, and no longer binds with it’s substrate More enzymes affected, the lower the reaction rate Allosteric sites can also be bound to by activators These can change the active site to help activate enzymes Inhibitors and activators can therefore be regulatory molecules

Control by regulation of enzyme action End product inhibition: Occurs as the concentration of an end product starts to accumulate Some of the end product can bind to an enzyme earlier in the pathway E.g. enzyme 1 This stops any further conversion of substrates by enzyme 1 Once end product concentration goes back to normal, it will no longer bind to enzyme 1 - pathway can resume Process is known as negative feedback - very finely tuned Feedback inhibition animation