Higher Biology | Key Area 2.1: Metabolic Pathways

Metabolic pathway

- A series of integrated and controlled pathways of enzyme-catalysed reactions within a cell, which start with a substrate and finish with an end product.

- Enzymes control and coordinate metabolic pathways by choosing the substrate at each step to get the final product.

- Most reactions are linked, and the energy given off by one pathway is used to power another.

Cell metabolism

The collective name for all biochemical reactions occurring within a living cell. These reactions form metabolic pathways.

Metabolic pathways can have three routes:

- Reversible steps, which many pathways are, where reactions can go back and forth.

- Irreversible steps, where reactions cannot be undone.

- Alternative routes, where to yield the same product (but often taking longer) alternative pathways are taken when specific enzymes or pathways are unavailable, or pathways are energetically unfavourable.

Some metabolic reactions are reversible. How are these controlled?

- The presence of a substrate or the removal of a product will drive a sequence of reactions in a particular direction.

- eg. presence of metabolite A activates enzyme 1, and metabolite A is converted into metabolite B. Presence of B activates 2, etc.

- If metabolite C is unusually high, and metabolite B is low, enzyme 2 works in reverse to convert C back to B.

Reactions within metabolic pathways can be one of two types:

Anabolic or catabolic

Anabolic reaction

A reaction that requires energy to build up large, complex molecules from small, simple molecules, eg. photosynthesis, where plants make glucose molecules from raw materials.

Catabolic reaction

A reaction that releases energy from the breakdown of larger, complex molecules to small, simple molecules, often providing building blocks. eg. food digestion, where enzymes break down food so they can be absorbed.

Enzyme

A vital protein involved in metabolic pathways, able to speed up reaction rates without being used up, and reduce activation energy cost. Their activity depends on their flexible and dynamic shape.

Enzyme active site

A groove or pocket formed by the folding pattern of a protein, particular to one substrate. This specificity is determined by a protein’s 3D structure, chemical and electrical properties of amino acids, and cofactors within active sites.

Proteins

Embedded in the phospholipid bilayer which makes up the membrane, and may act as:

- Pores, allowing molecules to pass through the membrane.

- Pumps, actively pumping molecules inside or outside the cell, allowing molecules to pass through the membrane (requires energy).

- Enzymes, which catalyse reactions and lower activation costs. Some proteins embedded in mitochondria and chloroplast membranes act as enzymes, eg. ATP synthase producing ATP from ADP + Pi

Membrane (plasma and internal cell membranes) in a cell play an important role in the control of metabolism. State some purposes:

- Membranes consist of proteins and phospholipids, with phospholipids creating a constantly moving bilayer, giving the membrane flexibility.

- Form surfaces for metabolic pathways to take place on, and allow high concentrations to be maintained in certain regions (allows maintenance of high reaction rates)

Channel-forming proteins

- Channel-forming proteins create pores which control the diffusion of small molecules across the cell.

- Some small molecules diffuse directly through the phospholipid layer, while larger molecules diffuse through pores created by channel proteins.

Active transport

- The movement of molecules against a concentration gradient from an area of lower to higher concentration, requiring energy in the form of ATP.

- Carrier proteins involved in active transport act as pumps and are specific to particular molecules (usually ions), eg. sodium-potassium pump

Metabolic pathways are controlled by:

- The presence or absence, and regulation of the rate of reaction of particular key enzymes.

- Temperature and pH can affect enzyme activity and subsequently rate of a metabolic pathway.

Activation energy

The energy required to initiate a reaction (an entry barrier a substrate must overcome).

Why do enzymes lower activation energy required for a reaction?

The active site holds molecules in a particular orientation, allowing bonds to be made or broken easier (ie. bind or break readily).

Enzyme affinity

The strength by which two or more molecules interact or bind (for enzymes, attraction between the active site of an enzyme and substrate).

Describe the affinity of an enzyme’s substrate and product.

- Substrate molecules have high affinity for the active site of an enzyme, allowing the substrate to bind easily to the active site.

- Product molecules of enzyme reactions have low affinity for the active site, allowing products to leave and the active site to bind with another substrate.

Induced fit

When the active site of an enzyme (which is flexible) changes shape to better fit or accommodate the substrate after the substrate binds. This creates a better binding arrangement between enzyme and substrate, lowering activation energy.

Substrate concentration on reaction rate

- As substrate concentration increases, the rate of an enzyme-controlled reaction increases. More active sites will be occupied by substrate, therefore more enzyme-substrate complexes are formed.

- If either substrate or enzyme concentration is limited, the rate of reaction will plateau and remain constant.

- With limited substrate concentration, active sites remain unoccupied. With limited enzyme molecules, substrate molecules have no active sites to occupy (ie. the enzyme is saturated).

Enzyme inhibitor

A substance which reduces the rate of an enzyme-catalysed reaction by interfering with the enzyme in either permanent or temporary ways.

Name the three types of enzyme inhibition:

- Competitive inhibition

- Non-competitive inhibition

- Feedback inhibition

Competitive inhibition

- Occurs when an inhibitor molecule binds to the active site of an enzyme, preventing the substrate from binding.

- Competitive inhibitors will have shapes that match the active site in some way (ie. they have similar molecular shapes to the substrate).

- Temporary, and can be reversed by increasing substrate concentration. Inhibitor concentration diluted to increase chances of substrates colliding and binding to an enzyme (overcoming inhibition).

- Reaction rate reaches maximum when substrate outnumbers inhibitor.

Give an example of a competitive inhibitor molecule:

Sarin

Non-competitive inhibition

- Occurs when an inhibitor molecule binds at an allosteric site, changing the shape of the active site and preventing the substrate from binding.

- A change in an enzyme’s 3D structure means it can no longer catalyse reactions. They do not compete with substrate molecules.

- Permanent, and cannot be reversed. Increasing substrate concentration has no effect.

- Most enzymes become inactivated, but some will be unaffected. Reaction rate remains low and plateaus early.

Give examples of a non-competitive inhibitor:

Cyanide, silver, mercury

Feedback inhibition

- Occurs when the end product in a metabolic pathway reaches a critical concentration.

- End product inhibits an earlier allosteric enzyme that catalyses the commitment step of that pathway.

- Blocks pathway and prevents further synthesis of the end product.