1. Section 6 – Metabolism & Enzymes
Unit 1 – Human Cells

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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)

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

18. 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

19. 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

20. 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

21. 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