Enzymes

Dr. Noha Soliman

Enzyme Regulation

1.Feedback control:Regulation process where the product of a series of enzyme-catalyzed reactions inhibits an earlier reaction in the sequence.

3.Isozymes or Isoenzymes:

Different form of the same enzyme.

They perform the same catalytic function.(Catalyze same reactions but are formed from structurally different polypeptides).

Different Isoenzymes may arise from different tissues and their specific detection may give clues to the site of pathology.

Functional plasma enzymes

( Plasma derived enzymes) Certain enzymes, proenzymes,

and their substrates are present at all times in the circulation of normal individuals and perform a physiologic function in the blood.

Examples of these functional plasma enzymes include the proenzymes of blood coagulation.

The majority of these enzymes are synthesized in and secreted by the liver.

Nonfunctional plasma enzymes

(Cell derived enzymes) -Plasma also contains numerous

other enzymes that perform no known physiologic function in blood.

Arise from the routine normal destruction of erythrocytes, leukocytes, and other cells.

Tissue damage or necrosis resulting from injury or disease is generally accompanied by increases in the levels of several nonfunctional plasma enzymes.

Enzymes as

Diagnostic

tools

The measurement of the serum levels of numerous enzymes has been shown to be of diagnostic significance.

This is because the presence of these enzymes in the serum indicates that tissue or cellular damage has occurred resulting in the release of intracellular components into the blood &this increases the level of certain enzymes in blood according to the damaged organ.

How?

Presence of disease.

Organs involved.

Etiology /nature of disease: differential diagnosis.

Extent of disease-more damaged cells-more leaked enzymes in blood.

Information from enzymes measurements in serum?

Measurement of enzyme activity

Enzyme activity is expressed in International unit (IU):

-It corresponds to the amount of enzymes that catalyzes the conversion of one micromole (mol) of substrate to product per minute.

WHAT ARE THE ENZYMES MOST

USED IN

THE DIAGNOSIS OF CERTAIN DISEASES?

Plasma enzymes

Functional Non functional

**For example:-

3-Alanine transaminase(ALT) 4-Aspartate transaminase(AST)

5-Alkaline phosphatase 6-Acid phosphatase

7-Amylase & Lipase enzymes

Isoenzymes1-Lactate dehydrogenase(LDH)2-Creatine kinase(CK)

Lactate dehydrogenase(LDH)

Lactic acid Pyruvic acid

NAD NADH+H

LDH is elevated in myocardial infarction, blood disorders.

It is a tetramer protein and made of two types of subunits namely H = Heart, M = skeletal muscle.

It exists as 5 different isoenzymes with various combinations of H and M subunits.

Isoenzyme name

Composition Composition Present in Elevated in

LDH1 ( H4) HHHH

Heart, RBC myocardial infarction

LDH2 (H3M1) HHHM Heart, RBC myocardial infarction

LDH3 (H2M2) HHMM lungs and spleen

leukemia

LDH4 (H1M3) HMMM lungs and spleen

viral hepatitis

LDH5 (M4) MMMM Skeletal muscle, Liver

Skeletal muscle and liver diseases

Creatine kinase (CK)

Creatine Creatine phosphate

ATP ADP

Creatine kinase is a dimer made of 2 monomers.

Skeletal muscle contains M subunit, Brain contains B subunits.

Three different isoenzymes are formed.

(Phosphocreatine – serves as energy reserve during muscle contraction)

Isoenzyme name Composition Present in Elevated in

CK-1 BB BrainCNS diseasesbrain tumors

CK-2 MB HeartAcute myocardial infarction

CK-3 MM Skeletal muscle

Skeletal muscle diseases

Alanine transaminase(ALT) It is also called Serum glutamic pyruvic transaminase(SGPT).

This enzyme is found predominantly in hepatocytes.

It increases in liver & heart diseases.

ALT is more specific for liver disease than AST.

Glutamic oxalacetic transminase(SGOT)Aspartate transaminase(AST)

*It is also called Serum glutamic oxaloacetic transaminase(SGOT)

*It increases in liver & heart diseases.

Alkaline phosphatase**It is found in the bone , liver, intestine, placenta.

**Increases mainly in bone and liver diseases.

Acid phosphatase**is found in the prostate, red blood cells, bone, liver, and pancreas.

** Mostly used to detect prostatic carcinoma.

**Amylase and lipase enzymes increase in diseases of the pancreas as acute pancreatitis

Summary-Enzymes as diagnostic markersMajor diagnostic use Origin EnzymeMyocardial infarction Heart, liver, muscle,

RBCLactate dehydrogenase (LDH)

Muscle diseaseMyocardial infarction

Skeletal MuscleHeart MuscleBrain

Creatine kinase (CK)

Viral hepatitis Heart and Liver Alanine aminotransferase (ALT) Serum glutamate-pyruvate transaminase (SGPT)

Liver and heart disease Heart and Liver Aspartate aminotransferase (AST) Serum glutamate-oxaloacetate transaminase (SGOT)

Liver and bone disease Hepatobiliary treeBone, placenta

Alkaline phosphatase (ALP)

Prostate cancer Prostate, erythrocytes Acid phosphatase (ACP)

Acute pancreatitis Pancreas, Salivary glands

Amylase

Acute pancreatitis Pancreas Lipase

Thank you