8.1 Essential ideas

8.1.1 Metabolism

  • In 2.1.1, you learned that metabolism is the complete web of all enzyme-catalysed reactions in a cell.
  • A single metabolic pathway consists of a series of biochemical reactions. At each step of the pathway, a different enzyme is necessary to produce metabolic intermediates from reacting substrates. At the final step, there is an end-product.
  • Metabolic pathways can consist of chains or cycles of enzyme-catalysed reactions.

Figure 8.1.1a – Examples of metabolic pathwaysFigure 8.1.1a – Examples of metabolic pathways:
a) Synthesis of serine (chain pathway) b) Krebs cycle (cycle pathway).

Enzymes lower activation energy

  • In order to react biochemically, substrates need to be activated into a high-energy state, called the transition state.
  • In the transition state, bonds within the substrates are weakened and products are formed easily.
  • The energy required for substrates to reach the transition state is called activation energy. Enzymes catalyse reactions by lowering the activation energy needed for substrates to reach the transition state.

Figure 8.1.1b – Enzyme effect on activation energy in an exergonic reaction (left) and an endergonic reaction (right).Figure 8.1.1b – Enzyme effect on activation energy in an exergonic reaction (left) and an endergonic reaction (right).

Enzyme inhibition

  • Metabolic pathways are regulated by inhibition. Inhibitors are chemical substances that bind to enzymes and reduce their activity.
  • Inhibitors may be competitive or non-competitive.

Figure 8.1.1c – Competitive and non-competitive inhibitionFigure 8.1.1c – Competitive and non-competitive inhibition

 

Competitive inhibitor

Non-competitive inhibitor

Structure

Similar to substrate

Different from substrate

Binding site

Enzyme active site

Away from active site, often an allosteric site

Effect

Blocks access to active site, no reaction

Reduces access to binding site, or changes conformation of active site, no reaction

Examples

i. Oxygen competes with carbon dioxide for the active site of RuBisco during photosynthesis
ii. Malonic acid competes with succinic acid for the active site of succinic dehydrogenase in the Kreb’s cycle. 

i. Potassium cyanide interferes with the active site of cytochrome oxidase enzymes during aerobic respiration.

ii. Penicillin alters the active site of DD- transpepsidase, preventing the synthesis of peptidoglycan cross-links in bacterial cell walls. (Allosteric inhibition)

 

End-product inhibition

  • Organisms must produce and utilise metabolites efficiently in order to conserve energy and prevent the accumulation of potentially toxic substances.
  • Some metabolic pathways use end-product inhibition to regulate rates of production – when the end-product accumulates without being utilised, it inhibits an enzyme earlier in the pathway and prevents further production.

Figure 8.1.1d – End-product inhibition of the threonine – isoleucine pathwayFigure 8.1.1d – End-product inhibition of the threonine – isoleucine pathway

  • End-product inhibition is an example of negative feedback. The end-product can act as a competitive or a non-competitive inhibitor.
  • In the metabolic pathway shown above, isoleucine acts as a non-competitive inhibitor of threonine deaminase – the first enzyme in the pathway.

Essential idea

Metabolic reactions are regulated in response to the cell’s needs.

Figure 8.1.1e – Metabolic pathwaysFigure 8.1.1e – Metabolic pathways
The same metabolites can be part of many metabolic pathways, but each reaction requires a unique enzyme.

Figure 8.1.1f – Malonic acidFigure 8.1.1f – Malonic acid
The competitive inhibitor malonic acid (above) has a similar structure to succinic acid (below)

Figure 8.1.1g – Succinic acidFigure 8.1.1g – Succinic acid

Concept help

Non-competitive inhibitors bind at a site other than the active site. Allosteric inhibition is one type of non-competitive inhibition. In other types of non-competitive inhibition, the inhibitor does not prevent the substrate from binding to the active site, but still prevents catalysis because it is bound to the enzyme.

Figure 8.1.1h – Non-competitive inhibitionFigure 8.1.1h – Non-competitive inhibition

Food for thought

We often say that enzymes 'speed up' reactions. The reality is that biochemical reactions would not occur without enzymes.

Figure 8.1.1i – Glucose powderFigure 8.1.1i – Glucose powder
Glucose powder exposed to oxygen in the air will NEVER undergo aerobic respiration without enzymes.

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