786786ENENZYZYMOMOLOLOGYGY

:Topic of stage

& REGULATORY ENZYMES THEIR ROLE

:Speaker

FAREES UD DIN MUFTI

OBJECTIVESOBJECTIVES

What are EnzymesWhat are Enzymes Hello to Regulatory enzymesHello to Regulatory enzymes Types of Regulatory EnzymesTypes of Regulatory Enzymes

1.1. Allosteric Regulatory EnzymesAllosteric Regulatory Enzymes

2.2. Covalently Modulated Regulatory EnzymesCovalently Modulated Regulatory Enzymes Overview the Role of Regulatory EnzymesOverview the Role of Regulatory Enzymes

1.1. Monoamine Oxidase AMonoamine Oxidase A

2.2. ADP-Glucose PyrophosphorylaseADP-Glucose Pyrophosphorylase

3.3. PhosphofruktokinasePhosphofruktokinase

4.4. Tyrosine HydroxylaseTyrosine Hydroxylase

ENZYMESENZYMES

They are bio molecules acting as catalysts.They are bio molecules acting as catalysts. Protein in nature.Protein in nature. Accelerating the reactions of living processes.Accelerating the reactions of living processes. Enzymes don’t consume themselves.Enzymes don’t consume themselves. Do’nt change equilibrium but only enhance reaction rate.Do’nt change equilibrium but only enhance reaction rate. They are highly specific and react with only one substrate to They are highly specific and react with only one substrate to

form one product and can enhance reaction rates by as much form one product and can enhance reaction rates by as much as 1017 times.as 1017 times.

Regulatory EnzymesRegulatory Enzymes

As the name indicate, it has regulatory function i.e. can As the name indicate, it has regulatory function i.e. can undergo a change in catalytic activity.undergo a change in catalytic activity.

OROR A regulatory enzyme is an enzyme in a biochmeical pathway A regulatory enzyme is an enzyme in a biochmeical pathway

which, through its responses to the presence of certain other which, through its responses to the presence of certain other biomolecules, regulates the pathway's activity. This is usually biomolecules, regulates the pathway's activity. This is usually done for pathways whose products may be needed in different done for pathways whose products may be needed in different amounts at different times, such as hormone production.amounts at different times, such as hormone production.

Regulatory enzymes exist at high concentrations so its activity Regulatory enzymes exist at high concentrations so its activity can be increased or decreased with changes in substrate can be increased or decreased with changes in substrate concentrations.concentrations.

TypesTypes

Type 1)Type 1) Allosteric Regulatory EnzymesAllosteric Regulatory Enzymes

Having two binding sites on its surface.Having two binding sites on its surface. The substrate binds to one site, whereas, a metabolite which The substrate binds to one site, whereas, a metabolite which

can be a modulator, binds to the another site.can be a modulator, binds to the another site. The binding of modulator is non covalent and is reversible.The binding of modulator is non covalent and is reversible. When modulator binds to allosteric enzyme , enzyme When modulator binds to allosteric enzyme , enzyme

undergoes a conformational change in its structure, because undergoes a conformational change in its structure, because of which enzymes cannot produce its substrate and enzyme of which enzymes cannot produce its substrate and enzyme activity gets regulated.activity gets regulated.

Example: Aspartate transcarbamoylase,Example: Aspartate transcarbamoylase, an enzyme in an enzyme in pyrimidine synthesis.pyrimidine synthesis.

Allosteric enzymes undergo conformational changes in response Allosteric enzymes undergo conformational changes in response to modulator binding based on its kinetics properties.to modulator binding based on its kinetics properties.

Based on modulation, allosteric enzymes can be sub-grouped into Based on modulation, allosteric enzymes can be sub-grouped into two categories:two categories:

(i)(i) Homotropic allosteric enzymeHomotropic allosteric enzyme

In which both the substrate and the effector plays part in the In which both the substrate and the effector plays part in the modulation of the enzyme, which in turn affects the enzyme modulation of the enzyme, which in turn affects the enzyme catalytic activity.catalytic activity.

(v)(v) Heterotropic allosteric enzymesHeterotropic allosteric enzymes

In which only the effector performs role of modulation.In which only the effector performs role of modulation. At this junction the allosteric site of the enzyme can be At this junction the allosteric site of the enzyme can be

one(monovalent) or two and more (polyvalent).one(monovalent) or two and more (polyvalent).

Type 2)Type 2) Covalently Modulated Regulatory EnzymesCovalently Modulated Regulatory Enzymes

•This type of regulatory enzyme has covalent bond that can interconvert the enzyme in two forms.•One of the form has more activity and other form has less / negligible activity.•This interconversion is carried out by another enzyme that can regulate the enzyme activity.

•Example: Glycogen phosphorylase.•This enzyme has phosphorylase A as active form and phosphorylase B as inactive form.•Phosphorylase phosphatase and phosphoryl kinase are the enzymes that carryout the inter conversion between these A (active) and B (inactive) forms.

Role Of Regulatory EnzymesRole Of Regulatory Enzymes

1)1) Role of regulatory enzyme (MONOAMINE OXIDASE) in Lungs Role of regulatory enzyme (MONOAMINE OXIDASE) in Lungs and damage of Smokingand damage of Smoking

Most fascinating role of regulatory enzyme in lungs is of Monoamine Most fascinating role of regulatory enzyme in lungs is of Monoamine oxidase (MAO) A which breaks down many compounds that affect oxidase (MAO) A which breaks down many compounds that affect blood pressure, and the lung is a major metabolic organ in degrading blood pressure, and the lung is a major metabolic organ in degrading some of these compounds. some of these compounds.

Cigarette smoking accounts for 440,000 deaths each year in the United Cigarette smoking accounts for 440,000 deaths each year in the United States, or nearly one of every five deaths, according to the Centers for States, or nearly one of every five deaths, according to the Centers for Disease Control and Prevention.Disease Control and Prevention.

Smoking kills more Americans than AIDS, illegal drugs, alcohol, car Smoking kills more Americans than AIDS, illegal drugs, alcohol, car accidents, suicides and murders combined and increases one's chances accidents, suicides and murders combined and increases one's chances of developing lung, bladder, esophageal and throat cancers; chronic lung of developing lung, bladder, esophageal and throat cancers; chronic lung diseases; and coronary heart and cardiovascular diseases. diseases; and coronary heart and cardiovascular diseases.

Smoking appears to reduce MAO A like key enzyme in the lungs.Smoking appears to reduce MAO A like key enzyme in the lungs.

During investigation of researcher who used positron emission tomography During investigation of researcher who used positron emission tomography (PET) scanning and a tracer chemical that binds to the specific enzyme (PET) scanning and a tracer chemical that binds to the specific enzyme monoamine oxidase (MAO Amonoamine oxidase (MAO A) to track MAO A levels in nine smokers ) to track MAO A levels in nine smokers and nine nonsmokers.and nine nonsmokers.

With whole-body PET imaging, researchers could measure the With whole-body PET imaging, researchers could measure the concentration and movement of the radiotracer and MAO A, a subtype of concentration and movement of the radiotracer and MAO A, a subtype of the enzyme crucial to mood regulation and one that breaks down chemical the enzyme crucial to mood regulation and one that breaks down chemical compounds that regulate blood pressure. compounds that regulate blood pressure.

The scans revealed that MAO A was fairly well "intact" in all of the The scans revealed that MAO A was fairly well "intact" in all of the

peripheral organs except in smokers' lungs, said researcher Miss. Fowler.peripheral organs except in smokers' lungs, said researcher Miss. Fowler.

Smokers had MAO A levels that were 50 percent lower than in Smokers had MAO A levels that were 50 percent lower than in nonsmokers, she said, noting that a prior study had also shown nonsmokers, she said, noting that a prior study had also shown a significant reduction of MAO A in smokers' brains.a significant reduction of MAO A in smokers' brains.

So reduced levels of MAO A in smokers' lungs may be a So reduced levels of MAO A in smokers' lungs may be a significant factor contributing to some of the physiological significant factor contributing to some of the physiological effects of smoking, including changes in blood pressure and effects of smoking, including changes in blood pressure and pulmonary function. pulmonary function.

In conclusion she said that "These studies showing for the first In conclusion she said that "These studies showing for the first time that smokers have reduced levels of MAO (A) in lungs time that smokers have reduced levels of MAO (A) in lungs and MAO (B) in their brains and in certain peripheral organs and MAO (B) in their brains and in certain peripheral organs shed mechanistic light on some of the more puzzling aspects shed mechanistic light on some of the more puzzling aspects of smoking, including a reduced rate of Parkinson's disease in of smoking, including a reduced rate of Parkinson's disease in smokers and a high rate of smoking among people with smokers and a high rate of smoking among people with depression and those addicted to other substances,”.depression and those addicted to other substances,”.

1)1) Role of Regulatory enzyme (ADP-Glucose Role of Regulatory enzyme (ADP-Glucose Pyrophosphorylase), in Bacterial Glycogen SynthesisPyrophosphorylase), in Bacterial Glycogen Synthesis

In bacteria and plants, the synthesis of glycogen and starch In bacteria and plants, the synthesis of glycogen and starch occurs by utilizing ADP-glucose as the glucosyl donor for occurs by utilizing ADP-glucose as the glucosyl donor for elongation of the -1,4-glucosidic chain.elongation of the -1,4-glucosidic chain.

The main regulatory step takes place at the level of ADP-The main regulatory step takes place at the level of ADP-glucose synthesis, a reaction catalyzed by ADP-Glc glucose synthesis, a reaction catalyzed by ADP-Glc

pyrophosphorylase (PPase).pyrophosphorylase (PPase).

1)1) Role of regulatory Enzyme the PFK (Phosphofruktokinase)in Role of regulatory Enzyme the PFK (Phosphofruktokinase)in neural activity maintenanceneural activity maintenance

Regulatory enzyme the (PHOSPHOFRUKTOKINASE) Regulatory enzyme the (PHOSPHOFRUKTOKINASE) helps in Glycolysis for maintenance of Synaptic activity helps in Glycolysis for maintenance of Synaptic activity (population spikes, PS) and on the level of high energy (population spikes, PS) and on the level of high energy phosphates in the region of dentate gyrus (DG), CA3 and phosphates in the region of dentate gyrus (DG), CA3 and CA1 area of hippocampal in guinea pigs.CA1 area of hippocampal in guinea pigs.

The sensitivity in maintaining synaptic activity to lowered The sensitivity in maintaining synaptic activity to lowered glucose concentrations showed good parallels with the glucose concentrations showed good parallels with the activity of PFK in these regions, indicating that non-activity of PFK in these regions, indicating that non-oxidative glycolytic metabolism regulated by PFK is crucial oxidative glycolytic metabolism regulated by PFK is crucial for the maintenance of synaptic activity.for the maintenance of synaptic activity.

1)1) Role of Regulatory enzymes (TYROSINE Role of Regulatory enzymes (TYROSINE HYDROXYLASE) in Parkinson’s diseaseHYDROXYLASE) in Parkinson’s disease

The major neuropathology of Parkinson's disease (PD) is the The major neuropathology of Parkinson's disease (PD) is the degeneration of nigrostriatal dopamine (DA), resulting in a deficiency of degeneration of nigrostriatal dopamine (DA), resulting in a deficiency of DA, and of the enzyme tyrosine hydroxylase (TH), which catalyzes the DA, and of the enzyme tyrosine hydroxylase (TH), which catalyzes the synthesis of L-dopa.synthesis of L-dopa.

The symptomatic treatment of PD consists of replenishing DA by The symptomatic treatment of PD consists of replenishing DA by administering L-dopa, which is enzymatically converted to DA in the administering L-dopa, which is enzymatically converted to DA in the striatum.striatum.

The increase of TH activity by modification of the enzyme leads to an The increase of TH activity by modification of the enzyme leads to an increased synthesis of striatal L-dopa, and thereby replenishes the increased synthesis of striatal L-dopa, and thereby replenishes the missing DA more efficiently. missing DA more efficiently.

Thus, modification of TH results in an activated form of the enzyme, Thus, modification of TH results in an activated form of the enzyme, which might provide a basis for developing new strategies in the which might provide a basis for developing new strategies in the treatment of PD. treatment of PD.

Thank Thank !you !you