Metabolic pathways

What do we mean by metabolism? Metabolism is the collective term for the thousands of biochemical _________ that occur within a living cell. These reactions are catalysed by __________ and are part of metabolic ____________. enzymes pathways reactions

Substance 1 Substance 2 Substance 3 Enzyme 1Enzyme 2 A (very) simple metabolic pathway: Substrate Intermediate Metabolite Product Enzyme 1Enzyme 2 __________

What do we mean by metabolism? Metabolism is the collective term for the thousands of biochemical reactions that occur within a living cell.

Six characteristics of metabolic pathways: These pathways are integrated (i.e. connected), they do not proceed in isolation. These pathways are tightly controlled. These pathways can have reversible and irreversible steps Metabolic pathways may exist that can bypass steps in a pathway thereby providing alternative routes. Enzymes often act in groups or as multi-enzyme complexes. DNA and RNA polymerases are part of multi-enzyme complexes. There are two types of pathways

Types of metabolic pathways Anabolic pathways: involve biosynthetic processes (e.g. _________synthesis). They __________ energy. Catabolic pathways: involve the breakdown of molecules (e.g. ______________). They __________ energy. Energy is transferred between __________ and ____________ pathways by ______. protein require respiration release catabolic anabolicATP

Catabolic pathway Anabolic pathway ATP Glucose + oxygen CO 2 + water Amino acids Protein

What do you remember about enzymes? They are proteins and can be denatured at high temperatures They speed up (i.e. catalyse) a chemical reaction that transforms substrate(s) into product(s) and do not get used up/ modified in the process. They have an active site in which the substrate binds.

Enzymes: activation energy

If there is enough _______energy given to a molecule, its chemical bonds will become highly unstable. This stage is called ___________state In the ___________state, chemical bonds can be ___________and a chemical reaction can take place. transition heat broken transition

Can this heat energy be provided within cells for chemical reactions to take place? NO! How can enzyme speed up reactions? Instead, the substrate(s) is being contorted by the enzyme into a highly unstable state (i.e. transition state) so that chemical bonds can be broken. The energy needed to contort the molecule into a highly unstable state is referred to as ACTIVATION energy.

Activation energy diagram

Enzymes lower the activation energy needed for a reaction to take place

Activation energy is the energy needed to contort the molecule into a highly unstable state (Transition state) so that chemical bonds can be broken and a chemical reaction can take place. Out with cells, this energy is provided in the form of heat energy. In cells, enzymes lower the activation energy needed for a chemical reaction so that they can take place at lower temperatures. Summary

Enzymes: active site and induced fit In N5: this was the story (not anymore!):

The active site of an enzyme is a groove or a hollow created by the chemical structure of and the bonding between the enzyme’s amino-acids.

The substrate shows affinity (chemical attraction) to the active site. The specificity of an enzyme is attributed to a compatible fit between the shape of its active site and that of its substrate.

When the reaction involves 2 or more reactants, the active site has a role in orientating reactants.

What is an active site? The active site of an enzyme is a groove or a hollow created by the chemical structure of and the bonding between the enzyme’s amino-acids. Why does the substrate bind to the active site? The substrate shows affinity (chemical attraction) to the active site. What the basis of the specificity of an enzyme? The specificity of an enzyme is attributed to a compatible fit between the shape of its active site and that of its substrate. When the reaction involves 2 or more reactants, what does the active site do? the active site has a role in orientating reactants. Active Site: summary

Induced fit

When the substrate enters the active site, the shape of the active site and that of the enzyme changes due to………… Induced fit

When the substrate enters the active site, the shape of the active site and that of the enzyme changes …….due to chemical interactions between the substrate and the active site. Induced fit

This change in shape is called the ______________and it makes the active site fit even more snuggly around the___________. As a result, the conditions for the chemical reaction to take place are optimized as the _____________needed to reach the ___________state is increased/lowered. induce fit substrate activation energy transition lowered

Homework: Booklet, Qs p18: 1,2,5,6,7,9,10 Book p85, Q

Control of metabolic pathways Regulation can be controlled by intracellular and extracellular signal molecules.

Control of metabolic pathways Genes only expressed sometimes e.g. lipase to digest fats Genes always expressed e.g. enzymes for respiration Genes always expressed e.g. enzymes for respiration What are the two types of genes that need to be regulated?

Control of metabolic pathways How are genes from these metabolic pathways controlled? Control by selective gene expression What does that mean? Genes coding for enzymes which are not always needed can be switched on/off. Control of MP is by the presence or absence of a particular enzymes. Genes only expressed sometimes e.g. lipase to digest fats

Control of metabolic pathways How are genes from these metabolic pathways regulated? Control through the regulation of the rate of reaction: Genes always expressed e.g. enzymes for respiration Genes always expressed e.g. enzymes for respiration Are you sure that you understand the meaning of the “rate of reaction?”

Rate of reaction: change of concentration of a substance per unit of time. Measured by either the decreasing concentration of the substrate or the increasing concentration of a product.

The rate of reaction is the speed of a reaction, i.e. how fast it happens. At a low rate of reaction, the reaction happens slowly. At a high rate of reaction, the reaction happens fast. A rate of reaction can increase (reactions happen increasingly faster) or decrease (reactions happen increasingly slower) Extra bit

Control of metabolic pathways The control through the regulation of the rate of reaction can take place in three ways: 1- control by the concentration of substrate/product 2- control through competitive and non- competitive inhibitor 3- control through feedback inhibition Genes always expressed e.g. enzymes for respiration Genes always expressed e.g. enzymes for respiration

1/ What is the limiting factor in A? A B The effect of substrate concentration on the rate of reaction

1/ What is the limiting factor in A? In A, the limiting factor is the substrate concentration A B The effect of substrate concentration on the rate of reaction

2/ As the reaction stopped in B? A B The effect of substrate concentration on the rate of reaction

2/ As the reaction stopped in B? Not, the rate of reaction is high, in other words the reaction takes place very quickly but at a steady rate. A B The effect of substrate concentration on the rate of reaction

3/ What is the limiting factor in B? (Why does the rate of reaction eventually stop increasing?) A B The effect of substrate concentration on the rate of reaction

3/ What is the limiting factor in B? (Why does the rate of reaction eventually stop increasing?) The limiting factor in B is not substrate concentration, nor temperature (enzymes are working at maximum rate), it has to be enzyme concentration (all active sites are involved in the reaction) or another sort of control such as feedback inhibition (see later). A B The effect of substrate concentration on the rate of reaction

1- control by the concentration of substrate/product. The presence of a substrate or the removal of a product will have an effect on both – the rate of reaction – drive a sequence of reactions in a particular direction, i.e. towards equilibrium. Control of the rate of reaction

. Most enzymatic reactions are reversible

Extra bit: Understanding chemical equilibrium When reversible reactions reach equilibrium the forward and reverse reactions are still happening but at the same rate, so the concentrations of reactants and products do not change.

Extra bit: Do enzymes change equilibrium? They don’t, they just make it happen faster.

1- control by the concentration of substrate/product 2- control through competitive and non- competitive inhibitor Control of the rate of reaction

Competitive inhibitor

Inhibitor molecule binds to active site. How can it be reversed? Remember, it is a competition! Competitive inhibitor

Competitive inhibition can be reversed by increasing substrate concentration. Competitive inhibitor

Non-Competitive inhibitors How do you think this may be different?

Non-Competitive inhibitors How do you think this may be different?

Non-Competitive inhibitors How do you think this may be different? Binding by the non-competitive inhibitor changes shape of active site so that it is no longer affinity to the substrate

A B Identify the type of inhibition with the graph (competitive or non-competitive)

A B A is competitive (at high substrate concentrations, the inhibitor as little effect on the rate of reaction) B is non-competitive, the rate of reaction with the inhibitor remains lower than without, independently of substrate concentration.

1- control by the concentration of substrate/product 2- control through competitive and non- competitive inhibitor 3- control through feedback inhibition Control of the rate of reaction

Control through feedback inhibition The end product binds to an enzyme that catalyses a reaction early in the pathway and inhibits its function.