Enzymes

Allostery Allostery The example of non-competitive inhibition above (Sarin gas) is harmful, but in the body many examples exist where the property is used to regulate metabolic pathways. Enzymes that behave in this way are called allosteric enzymes. Instead of the term inhibitor the term effector is used. Key points Quaternary level structure of the enzyme; At least two subunits; One subunit has the substrate active site; Other subunit has the effector binding site. The effector may be an activator or an inhibitor of the enzyme. The enzyme alternates between the active form that reacts with the substrate and the inactive form that does not. The allosteric activator stabilises the active form. The allosteric inhibitor stabilises the inactive form.

substrate Inactive form of enzyme Allosteric inhibitor

Active form of enzyme

Allosteric activator

The allosteric activator binds and stabilises the active form of the enzyme.

The allosteric inhibitor binds and stabilises the inactive form of the enzyme.

How then does this work to regulate a metabolic pathway? Phosphorylase is an enzyme in muscle that removes a glucose phosphate from the end of glycogen at the start of glycolysis. Remember that glycolysis is the first stage in producing ATP from glucose. If the muscle is resting it does not need much ATP and hence the relative concentration of ATP will be high. On the other hand if it is active then it will be using up ATP and the relative concentration of AMP (adenosine monophosphate) will be high. It therefore makes sense to regulate this key enzyme so that glycogen is not broken down unnecessarily and wasted. ATP and AMP act as the allosteric effectors.
glycogen glucose phosphate Allosteric activator AMP ATP Inactive phosphorylase glycogen cannot bind Allosteric inhibitor ATP

Active phosphorylase

AMP

Cell Respiration

Key points Electrons flow through a sequence of carriers that are proton pumps; At the final pump, cytochrome oxidase, they are added to oxygen and together with protons from the matrix form water; The energy from the electrons is used to pump protons from the matrix to the inter-membrane space; There are three linked proton pumps; Protons diffuse from the high concentration in the inter-membrane space back into the matrix via a channel linked to ATP synthetase; The energy from this proton flow is used to synthesis ATP; The thin inter-membrane space permits the rapid formation of a high proton concentration; NADH + H+ releases its electrons at the first pump thus generating 3 ATP; FADH2 releases its electrons at the second pump thus generating only 2 ATP.
Cristae

Oxidative Phosphorylation and The Chemiosmotic Theory

Outer membrane Thin inter-membrane space Inner membrane Matrix

An electron transport complex consisting of three proton pumps and an ATP synthetase channel. There are a great many of these all over the inner membrane.

NADH + H+

NAD+ ADP + Pi H+ e
+ 2H + O2

H+ ATP

H2O e-

H+ ATP synthetase

proton pump inner membrane H+ Only NADH + H+ is shown. FADH2 releases its electrons at the second pump thereby resulting in fewer protons pumped and hence less ATP synthesised. H+ H+ H+ H+ H+ H+ H+ outer membrane H+

As electrons from the carriers (NADH + + H and FADH2) flow through the pumps, protons are pumped into the intermembrane space creating a high concentration.

Protons diffuse down the concentration gradient through the protein channel and the ATP synthetase thereby generating ATP.