Substrate specificity of enzymes
-The reaction that an enzyme acts on is called the enzyme’s substrate.
-The enzyme binds to its substrate forming an enzyme-substrate complex
-The active site is the region on the enzyme where the substrate binds.
-Induced fit of a substrate brings chemical groups of the active site into positions that enhance their ability to catalyze the reaction.
in general enzymes are really big molecules their active site is typically small so the enzyme structure is designed to create the architecture that’s necessary to place individual amino acids from the polypeptide segmentes in the right place in 3D space in the active site so that substrates combine and chemistry can occur and so we need all that extra protein to create the structure that’s essential for insuring that the active site is formed correctly and finally induced feet so this is the idea:
Catalysis in the enzyme’s active site
In an enzymatic reaction, the substratet binds to the active site of the enzyme.
The active site can lower the EA barrier:
.) By orienting substrate correctly
.) Straining substrate bonds.
.) Providing a favorable micro environment
.) Covalently bonding to the substrate
Binding energy contributes to catalysis in multiple ways:
– Entropy reduction
– Substrate desolvation
– Inducted fit
Enzyme regulation
Enzyme cofactors
Enzyme inhibitors
Allosteric regulation
1) Cofactors help enzymes to function efficiently
2) Enzymes inhibitors bloc activity through different mechanism :
Competitive, Non competitive
3) Enzyme can be regulated by structural changes
Enzymes can have a really huge effect on reaction rate (the rate enhancement; that’s achieved by an enzyme is more than million X)
Enzymes enhance rates by a very large number .
This is the concept of lock and key.
The lock and key concept for the enzymes is that you have an enzyme that has a binding site for a substrate that is a perfect fit.
And this idea was proposed by Mill Fisher, famous chemist and the idea was that enzymes have incredible specificity for their substrates because they have a binding site that matches that substrate exactly in a chemical sense and this model change chemical reaction so dramatically, and we know that enzyme can have a really huge effect en reaction rates.
This model doses not explain (enzymes that works are structures that stabilize the substrate in the transitional state. If the enzyme binds too well, it is not a good enzyme because it does not help the substrate to approache the transitional state which is a high energy state) .That was the problem with the lock and key model.
In 1950 (nineteen fifties) Dan Coshland proposed a modification to the lock and key model; which he called induced fit.
That means the binding site rather than being an exact match to the structure of the substrates (that simply the lock and key model). It has a shape that is close but not exactly the same as for the substrate. But when the substrate binds there is a structural change that is induced in the enzyme. That actually pushes the substrate closer to the structure. That has in the transitional state.
The difference between lock and key and induced fit is that.
Hexokinase is a beautiful structural example where we see that the substrate coming in and the enzyme closing down around it and inducing a change in the enzyme an substrate binding and then enhances the rate at which the substrate is converted to product.
Cofactors
Cofactors are non-protein enzyme helpers .
Cofactors may be inorganic (such as a metal in ionic form) or organic. An organic cofactor is called coenzyme
Coenzymes include vitamins. Many enzymes have helpers
Cofactors:
1) Tightly bound cofactors are called prosthetic groups
(They are almost like extensions of the protein itself they may not be covalently attached but they are very tightly associated with the enzyme and the enzyme would not be efficient without that group and so that’s what we call prosthetic group)
2) Loosely bound cofactors are called coenzymes
3) An active enzyme lacking the cofactors is called an Apo enzyme the complete enzyme with its cofactor is called a holoenzyme.
Cofactors:
Organic cofactors often share a common chemical feature; can we see it?
Coenzyme A
If you pay attention, you will notice that.
They all have adenine ( adenine ring)
Cofactors:
NADH is reversibly oxidized to NAD during electron transport in cells.
Many enzymes contain common structural features that bind NAD/NADH
Regulation of enzyme activity
helps control metabolism
Chemical chaos would result if a cell’s metabolic pathways were not tightly regulated.
A cell does this by switching on or off the genes that encode specific enzymes or by regulating the activity of enzymes
Feedback inhibition
In feedback inhibition, the end product of a metabolic pathway shuts down the pathway.
Feedback inhibition prevents a cell from wasting chemical resources by synthesizing more product than is needed.
Exergonic VS. endergonic reactions
Exergonic reactions release energy to the system and exergonic reactions proceed spontaneously.
Endergonic reactions absorb energy from the system and endergonic reactions are not spontaneous.
ATP Powers Cellular Work by coupling exergonic reactions to endergonic reactions.
A cell does three main kinds of work:
– Chemical
– Transport
– Mechanical
To do work cells manage energy resources by energy coupling. The use of an exergonic process to drive an endergonic one.Most energy coupling in cell is mediated by ATP.
The structure and hydrolysis of ATP
ATP (adenosine triphosphate) is the cell’s energy shuttle.
ATP is composed of ribose (a sugar),adenine (a nitrogenous base) and three phosphate groups.
The bonds between the phosphate groups of ATP’s tail can be broken by hydrolysis.
Energy is released from ATP when the terminal phosphate bond is broken.
This release of energy comes from the chemical change to a state of lower free energy: not from the phosphate bonds themselves.
ATP Hydrolysis
How ATP Performs work
The three types of cellular work (mechanical, transport and chemical) are powered by the hydrolysis of ATP.
In the cell, the energy from the exergonic reaction of ATP hydrolysis can be used to drive an endergonic reaction.Overall, the coupled reactions are exergonic.
ATP drives endergonic reactions by phosphorylation. Transferring a phosphate group to some other molecule, such as a reactant.The recipient molecule is now phosphorylated.
The regeneration of ATP
ATP is a renewable resource that is regenerated by addition of a phosphate group to adenosine diphosphate (ADP).
The energy to phosphorylate ADP comes from catabolic reactions in the cell.
The chemical potential energy temporarily stared in ATP drives most cellular work.