Molecular Interactions in Cell events

(i) Catalysis

(ii) The Sodium-Potassium Pump

(iii) Cell Signalling

What caused this?

That’s clever

Bombardier Beetles Oxygen gas formed

during break down of H2O2 forces out water and other chemicals

Reaction releases a lot of heat so the water comes out as steam

A reminder of their importance Catalase breaks down 5 million molecules of

H2O2 per minute at 0oC, to protect cells.

It would take 300 years to break down the same number of molecules using iron as a catalyst

Chemical Reactions

Synthesis (anabolic) Condensation reactions

Removal of water to form a bond

Degradation (catabolic) Hydrolysis reactions

Addition of water to break a bond

Enzymes

Proteases Hydrolyse peptide bonds break down proteins into amino acids

Nucleases Hydrolyse phosphodiester bonds Break down nucleic acids into nucleotides

ATPases Hydrolyse ATP Break ATP into ADP and Pi with the release of

energy

Enzymes continued….

Kinases Catalyse the transfer of a phosphate group onto a

molecule such as a carbohydrate or a protein

Specificity of enzymes

Compare the two diagrams

Think about your knowledge of proteins tertiary structure? Why do you think the induced fit model is favoured?

Specificity of enzymes

Induced-fit model When substrate combines with the enzyme it

causes a change in shape of the active site The change in shape results in an optimal fit for

the substrate-enzyme interaction Once the product diffuses away, the enzyme

returns to its original shape

What analogy could be applied to this model?

What do the following have in common? Arsenic Nerve Gases

TabunSarin

Mercury

Cyanide DDT Lead Cadmium

Cyanide

Cyanide is found is a gas (sometimes liquid) Used / found in

House fires Apricot stones Suicide pills Gas chambers (both US and Nazi Germany) Stock piled by US and Soviet Union in 50’s and 60’s Mining Photography Electroplating

Cyanide

Binds to iron atom in the enzyme cytochrome C oxidase

This changes the shape of the enzyme Knowing how this works has important

applications for Detection of poisoning Treatment

Control of enzyme activity - Inhibitors Competitive Inhibitors

Decrease the rate of reaction Inhibitor is similar in structure and electrical

charge to substrate It binds to the active site An increase in the substrate can result in an

increase of product formation (inhibitor is out competed)

Competitive inhibition can be reversible or irreversible (depending on mechanism of binding)

Inhibitors cont..

Competitive inhibitors cont…

Inhibitors cont…

Non-competitive inhibitors Decrease the rate of reaction Inhibitors have no similarity to the substrate Inhibitor binds to part of the enzyme (other than

the active site) distorting the shape of the enzyme Increase in substrate concentration does not

increase product formation Can also be reversible

Inhibitors cont…

Non-competitive inhibition cont….

Control of enzymes – Enzyme modulators Allosteric enzymes

Allosteric enzymes have at least one other binding site than the active site (called an allosteric site)

Allosteric enzymes have 2 forms – active and inactive

When a substance binds to an allosteric site it changes the shape of the active site.

Positive modulation The modulator changes the active site so the enzyme

becomes active (substrate fits) Positive modulators are activators

Enzyme modulators cont…

Allosteric enzymes cont… Negative modulation

The modulator changes the active site so the enzyme becomes inactive

Negative modulators are inhibitors

Enzyme modulators cont….

Allosteric enzymes cont…

Control of enzymes – Covalent modifications

Addition, modification or removal of a variety of chemical groups

Changes the shape of the enzyme Phosphorylation and dephosphorylation

Kinase enzymes add phosphate Phosphatase enzymes remove phosphate Some enzymes are activated by phosphorylation,

others are inactivated (and vice versa for dephosphorylation)

Covalent modifications cont… Proteolytic cleavage

Conversion of an inactive enzyme to an active one Example Trypsinogen – Trypsin Trypsinogen is synthesised in the Pancreas Activation occurs when trypsinogen has amino acids

removed in the duodenum by another protease enzyme This changes the trypsinogen into the active form trypsin Trypsin then helps to activate more trypsinogen molecules

Back to cyanide

What type of inhibition is demonstrated by cyanide in the inhibition of cytochrome oxidase?

Enzyme inhibition is often how drugs work – targeting enzymes specific to other organisms, not humans

Control of metabolic pathways End product inhibition

Chemical reactions are normally organised into metabolic pathways with enzymes controlling each chemical reaction

The end-product can act as a negative modulator, binding to the first enzyme preventing the metabolic pathway from proceeding because intermediary substrates are not produced

This is a process of negative feedback

Learning Activities

Read and take notes from DART pg 61-68 Scholar 6.3 and 6.4 Check out

http://highered.mcgraw-hill.com/sites/0072437316/student_view0/chapter8/animations.html#

Find examples for each type of enzyme control Use flash cards to remember the enzymes and their reactions Draw posters of each type of enzyme control Use the information on ‘end-product inhibition in respiration’ to

demonstrate the principle of negative feedback ‘Enzymes’ worksheet ‘Enzyme cofactors and inhibitors’ worksheets Advanced Higher Biology Questions