Overview of Metabolism

Metabolism is the sum of all the chemical reactions that occur within a living organism. These reactions are essential for maintaining life, providing energy, synthesising new molecules, and breaking down waste products. At A-Level, it is vital to understand how metabolic pathways are organised, how ATP acts as the universal energy currency, and how enzymes control the rate and direction of metabolic reactions.

Key Definition: Metabolism is the totality of chemical reactions occurring within an organism, including both anabolic (building up) and catabolic (breaking down) processes.

Anabolism and Catabolism

Metabolic reactions fall into two broad categories:

Anabolism (Anabolic Reactions)

Anabolic reactions are biosynthetic processes that build larger, more complex molecules from smaller, simpler ones.
These reactions require an input of energy (they are endergonic).
Examples include:
- Protein synthesis — amino acids joined by peptide bonds to form polypeptides.
- DNA replication — nucleotides assembled into new DNA strands.
- Photosynthesis (Calvin cycle) — CO₂ and H₂O converted into glucose using light energy.
- Glycogen synthesis — glucose molecules linked together to form glycogen for storage.

Catabolism (Catabolic Reactions)

Catabolic reactions break down larger molecules into smaller ones, releasing energy.
These reactions are exergonic (energy-releasing).
Examples include:
- Cellular respiration — glucose broken down to CO₂ and H₂O, releasing energy for ATP synthesis.
- Digestion — large food molecules (starch, proteins, lipids) hydrolysed into monomers.
- Glycogenolysis — glycogen broken down into glucose-1-phosphate.

Feature	Anabolism	Catabolism
Direction	Small molecules → large molecules	Large molecules → small molecules
Energy change	Endergonic (energy required)	Exergonic (energy released)
Bond formation	Condensation reactions (new bonds formed)	Hydrolysis reactions (bonds broken)
Examples	Protein synthesis, photosynthesis	Respiration, digestion
Role of ATP	ATP is hydrolysed to provide energy	ATP is synthesised using released energy

Exam Tip: When describing metabolism in an exam, always specify whether a reaction is anabolic or catabolic and link this to the energy change involved.

Metabolic Pathways

Metabolic reactions do not occur in isolation. They are organised into metabolic pathways — sequences of enzyme-controlled reactions in which the product of one reaction becomes the substrate for the next.

Features of Metabolic Pathways

Each step is catalysed by a specific enzyme.
Pathways may be linear (e.g., glycolysis) or cyclical (e.g., Krebs cycle, Calvin cycle).
Intermediates in a pathway can serve as branch points, feeding into alternative pathways.
Pathways are compartmentalised within cells — different reactions occur in different organelles (e.g., glycolysis in the cytoplasm, Krebs cycle in the mitochondrial matrix).

Regulation of Metabolic Pathways

End-product inhibition (feedback inhibition) — the final product of a pathway inhibits an enzyme earlier in the pathway, preventing overproduction.
Allosteric regulation — regulatory molecules bind to an allosteric site on an enzyme, changing its shape and activity.
Reversible and irreversible inhibitors — competitive and non-competitive inhibitors modulate enzyme activity.

ATP: The Universal Energy Currency

Adenosine triphosphate (ATP) is the immediate source of energy for cellular processes. It is sometimes called the "energy currency" of the cell because it is used to transfer energy from catabolic reactions to anabolic reactions and other energy-requiring processes.

Structure of ATP

ATP consists of:
- Adenine — a nitrogenous base (purine).
- Ribose — a five-carbon sugar.
- Three phosphate groups — linked by high-energy phosphoanhydride bonds.
The bond between the second and third phosphate groups is the one most commonly hydrolysed to release energy.

ATP Hydrolysis

ATP is hydrolysed by the enzyme ATPase (or ATP hydrolase):
- ATP + H₂O → ADP + Pi + energy (~30.5 kJ mol⁻¹)
This is an exergonic reaction; the energy released is used immediately for cellular work.
The reaction is reversible — ATP can be resynthesised from ADP and Pi using energy from respiration or photophosphorylation.

ATP Synthesis

ATP is synthesised by the enzyme ATP synthase:
- ADP + Pi + energy → ATP + H₂O
ATP synthesis occurs during:
- Substrate-level phosphorylation — direct transfer of a phosphate group from a substrate to ADP (e.g., in glycolysis and the Krebs cycle).
- Oxidative phosphorylation — using energy from the electron transport chain in mitochondria.
- Photophosphorylation — using light energy in chloroplasts.

Why ATP is an Effective Energy Currency

Releases energy in small, manageable amounts — hydrolysis of one ATP releases ~30.5 kJ mol⁻¹, suitable for most cellular reactions (compared to glucose which releases ~2870 kJ mol⁻¹).
Rapidly regenerated — ATP turnover is extremely high; a resting human uses approximately 40 kg of ATP per day.
Water-soluble — easily transported within cells.
Universal — used by all living organisms.
Immediate — does not need to be further broken down; the energy is released in a single hydrolysis step.

Key Definition: ATP (adenosine triphosphate) is a nucleotide derivative that acts as the universal energy currency of cells, coupling exergonic and endergonic reactions.

The Role of Enzymes in Metabolism

Enzymes are biological catalysts — they speed up metabolic reactions without being consumed. Without enzymes, most metabolic reactions would proceed too slowly to sustain life.

How Enzymes Lower Activation Energy

Every chemical reaction requires a minimum input of energy to proceed — the activation energy (Eₐ).
Enzymes lower the activation energy by providing an alternative reaction pathway.
They do this by forming an enzyme-substrate complex: the substrate binds to the active site of the enzyme, which is complementary in shape and charge.
The induced fit model states that the active site changes shape slightly upon substrate binding, placing strain on bonds and lowering the activation energy.

Factors Affecting Enzyme Activity

Temperature — increasing temperature increases kinetic energy and the rate of enzyme-substrate collisions, up to the optimum temperature. Beyond this, the enzyme denatures as hydrogen bonds and other weak interactions break, altering the shape of the active site.
pH — each enzyme has an optimum pH. Deviations alter the ionisation of amino acid R-groups in the active site, reducing substrate binding.
Substrate concentration — at low concentrations, increasing substrate increases the rate of reaction. At high concentrations, all active sites are occupied (Vmax).
Enzyme concentration — increasing enzyme concentration increases the rate of reaction, provided substrate is in excess.

Coenzymes and Cofactors

Cofactors are non-protein molecules required by some enzymes for catalytic activity. They may be inorganic ions (e.g., Zn²⁺, Mg²⁺) or organic molecules.
Coenzymes are organic cofactors — they are not permanently bound to the enzyme and often act as carriers of chemical groups or electrons.
- NAD⁺ (nicotinamide adenine dinucleotide) — carries hydrogen atoms (electrons and protons) during respiration.
- FAD (flavin adenine dinucleotide) — another hydrogen carrier in the Krebs cycle.
- Coenzyme A (CoA) — carries acetyl groups in the link reaction and Krebs cycle.
- NADP⁺ — carries hydrogen atoms during photosynthesis.

Exam Tip: When discussing metabolism, always mention that each step is enzyme-catalysed. In longer essay answers, refer to the role of coenzymes such as NAD⁺ and FAD in transferring hydrogen to the electron transport chain.

Coupling Reactions

A fundamental principle of metabolism is that energy released by catabolic reactions is used to drive anabolic reactions. This coupling occurs via ATP:

Catabolic reactions (e.g., respiration) release energy → used to synthesise ATP from ADP + Pi.
ATP is hydrolysed → energy released drives anabolic reactions (e.g., protein synthesis, muscle contraction, active transport).

This coupling ensures that energy is not wasted as heat but is instead conserved in a usable form.

Summary

Metabolism comprises all anabolic and catabolic reactions in an organism.
Metabolic pathways are sequences of enzyme-controlled reactions, often compartmentalised within cells.
ATP is the universal energy currency, coupling energy-releasing and energy-requiring reactions.
Enzymes lower activation energy and are regulated by temperature, pH, substrate concentration, and inhibitors.
Coenzymes such as NAD⁺, FAD, CoA, and NADP⁺ play essential roles in metabolic pathways.