metabolism 2- energetics and enzymes Flashcards
What are enzymes.
A protein that acts as a catalyst to induce chemical changes in other substances, itself remaining apparently unchanged by the process. i.e. they can increase the speed at which a chemical reaction takes place by a factor of at least 1 x 106 yet at the same time, they exhibit quite exquisite specificity due to their conformation- don’t change equilibrium or free energy of reaction.
What is Von Gierke’s disease
The most common glycogen storage
disorder (1 in 100,000).
Autosomal recessive deficiency of
Glucose-6-Phosphatase
Clinical outcomes:
Hypoglycaemia, poor growth,
distended abdomen, seizures when
blood glucose is low- difficulty maintaining blood glucose conc.
Why is glucose-6-phosphatase important.
Glycogen is broken down into glucose-6-phosphate in the liver where it must then be broken down into glucose before it can enter the bloodstream.
In which forms do molecules in the cell posses energy
energy in the form of rotation and vibrations and also in the form of the bonds holding the various atoms together.
What is the first law of thermodynamics
Energy can neither be created nor destroyed. i.e. it is simply converted from one form to another.
What is the second law of thermodynamics
In any isolated system, e.g. a single cell or the universe, the degree of disorder can only increase.
What is entropy
The amount of disorder in a particular system
How do spontaneous reactions take place
Reactions proceed spontaneously towards products with greater entropy (i.e. more disorder). i.e when delta G is negative.
How are cells well ordered.
This is achieved by taking energy from the environment surrounding the cell and investing it in chemical reactions which maintain order- such as making peptide bonds.
What happens as cells become more ordered
Reactions which create order release heat- which increases the disorder of the surroundings.
Define Gibbs’ free energy
(Gibb’s) Free Energy is defined as the amount of energy within a molecule that could perform useful work at a constant temperature. (kJ/mole)
Why do we need to couple reactions.
Pathways within the cell that synthesise molecules are generally energetically unfavourable e.g. peptide synthesis- order is created- hence cannot take place spontaneously.
They take place because they are coupled to an energetically favourable one- hydrolysis of ATP does this.
Providing that the sum of the DG for the overall reaction is still negative, the reaction will proceed.
The majority of energetically unfavourable biochemical reactions rely on the hydrolysis of high-energy phosphate bonds such as those found in ATP.
What are phosphoanhydride bonds
Anhydride bonds (in red) link the terminal phosphate groups.
What is the delta G of ATP hydrolysis
-31 kJ/mole
Describe the coupling of the reaction to convert glucose to sucrose with the hydrolysis of ATP
Glucose + ATP — Glucose-1-phosphate + ADP
G1P + Fructose — Sucrose
Describe the changes in free energy in a reaction
Increases from substrate to transition state of substrate- difference in free energy is the activation energy. Free energy decreases from transition state of substrate to product. Enzymes lower the activation energy for the reaction.
What is the transition state of the substrate.
The transition state is the particular conformation of the substrate in which the atoms of the molecule are rearranged both geometrically and electronically so that the reaction can proceed.
Enzymes work by bending their substrates in such a way that the bonds to be broken are stressed and the substrate molecule resembles the transition state- lowers the transition state.
This makes them more amenable to reaction with other molecules.
How does the active site interact with the substrate
Enzymes bind one or more substrate molecules tightly within a part of the protein known as the active site.
Enzymes arrange the substrate(s) in such a way that certain bonds are strained. Key residues within the enzyme participate in either the making or breaking of bonds by altering the arrangement of electrons within the substrate(s).
This can often take the form of either oxidation reactions, (in which electrons are removed from an molecule) or reduction reactions (in which electrons are added to a molecule) .
Since the cellular environment is generally aqueous, often, when a molecule gains an electron, it also simultaneously
gains a proton. e.g. A + e- + H+ AH
Describe the lock and key model
In this model, the shape of the substrate (key) matches that of the active site (lock) of the enzyme. This model explains the specificity of most enzymes for a single substrate.
Describe the induced fit model
In this model, the substrate induces a change in the conformation of the enzyme which results in the formation of the active site. Upon release of products, the enzyme reverts back to its original conformation.
How do we know that the induced fit model is valid
From crystallographic analysis of enzymes with and without substrate bound, we now hold the induced fit model to be valid. There is a change in conformation of the enzyme when the substrate is bound- showing that there is an interaction between the substrate and enzyme.
What is the function of lysozyme
Lysozyme is a component of tears and nasal secretions and is one of the first lines of defence against bacteria.
It catalyses the hydrolysis of sugar molecules within bacterial cell walls that are necessary for their structure. With this bond broken, the bacteria lyse and die.
What exactly does lysozyme hydrolyse
Lysozyme hydrolyzes alternating polysaccharide copolymers of N-acetyl glucosamine (NAG) and N-acetyl muramic acid (NAM) which represent the “unit” polysaccharide structure of many bacterial cell walls.
Lysozyme cleaves at the b(1-4) glycosidic linkage, connecting the C1 carbon of NAM to the C4 carbon of NAG.
What is the function of Glu35 in the non-polar environment in the action of lysozyme
protonates the Oxygen in the glycosidic bond between NAM and NAG- breaking it- it then deprotonates an approaching water molecule- returning to its original state to continue catalysis. Hydroxide ion attacks the NAM
