enzymes 2012

ENZYMESENZYMES

Atif H. Khirelsied, B.Sc., M.Sc., Ph.D

Department of Biochemistry

Faculty of Medicine

International University of Africa, Khartoum, Sudan

Enzymesy

• Enzymes are biological catalysts.

• Catalyst: a molecule or element that speeds up a chemical reaction without being used up in the reaction.

• Almost every life process is dependent on enzymes. y p p y

• Almost all enzymes are protein except ribozymesAlmost all enzymes are protein, except ribozymes.

Enzymes structureEnzymes structure

• Enzyme are large globular protein• Enzyme are large globular protein molecules.

• Have a cleft (groove) that binds the substrate (active site)substrate (active site).

h d f• The nature and arrangement of amino acids in the active site make it specific for only one type ofit specific for only one type of substrate.

Enzymes nomenclature

• Traditionally, enzymes were simply assigned names by the

investigator who discovered the enzyme.

– By adding the suffix “ase” to the name of the substrate y g

e.g., lipases, amylases, proteases.

– By the type of reaction catalyzed e.g., alcohol

dehydrogenasedehydrogenase.

– Exceptions include older names like trypsin, pepsin, etc.

Enzymes classification and nomenclature

Systematic functional classification and nomenclature adopted by the IUBMB.

Enzymes are classified and named according to the nature of their chemical reactionsof their chemical reactions.

There are six major classes of enzymatic reactions.


Additional information on the sub‐subclasses and sub‐sub‐subclasses (ie, full enzyme classification and names) can be found at the referenced web link. http://www chem qmul ac uk/iubmb/enzyme/index htmlhttp://www.chem.qmul.ac.uk/iubmb/enzyme/index.html


• Each enzyme is assigned two words name and a four‐digits• Each enzyme is assigned two words name and a four‐digitsnumber.

• The name consist of its substrate(s) followed by a word ending in ‐ase specifying the type of reaction.

• For example, the enzyme (aconitase) is: aconitateh d t d it b i EC 4 2 1 3hydratase and its number is EC 4.2.1.3.

(“EC” stands for Enzyme Commission)


• The IUBMB assigns a 4 digit code to each enzyme• The IUBMB assigns a 4‐digit code to each enzyme.

E h i fi d b EC f ll d b h di i• Each enzyme is prefixed by EC, followed by the digits.For example: oxidoreductases EC 1.1.1.1

• Read more at:h // h l k/ b b/ / d h lhttp://www.chem.qmul.ac.uk/iubmb/enzyme/index.html


EC 1.1.1.1

The specific4th digit

EC: Enzyme Commission

The specific enzyme No

1st digit 3rd digitOxidoreductases e acceptor is

NAD+ or NADP+2nd digit

g

Dehydrogenasesacting on the CH‐OH GroupOH Group

Enzymes properties

1. Highly specific• absolute specificity

• relative specificityg y p p y

• Stereo‐specificity.

2. Extremely efficient.

a) Increase reaction rates by million times

b) Cause the reactions to proceed under mild conditions. ) p

c) Are not consumed during the course of reaction.

3. Have capacity for regulation.

Substrates bind to the enzyme’s active siteSubstrates bind to the enzyme s active site

• The active site is a groove where substrate binds via non• The active site is a groove where substrate binds via non‐covalent interactions

• Catalytic site = where reaction takes place• Catalytic site = where reaction takes place

Enzymes do not alter the reaction equilibrium constant, they lower the energy of activation.

Substrates bind to the enzyme’s active site

• Substrates bind in active site by weak non‐covalent interactions– A. hydrogen bondingB h d h bi i t ti– B. hydrophobic interactions

– C. ionic interactions

• Enzymes interact with their substrates to effect catalysis.

E + S ↔ ES ↔ EP ↔ E + P

“Key and lock” hypothesis– To explain enzyme substrate specificity.

Key and lock hypothesis

– Emil Fischer in 1894 suggested that the active site of an enzyme is structurally complement to substrate.

“Induced‐fit” hypothesis

– In 1958 Daniel Koshland suggested a modification to theIn 1958, Daniel Koshland suggested a modification to the

lock and key model.

d h h b b h– He proposed that when a substrate combines with an

enzyme, the structure of the enzyme is induced to change

for effective catalytic function.

“Induced‐fit” hypothesis

Some enzymes require cofactors

C f tCofactor‐ small molecules required for the catalytic activity of

enzymes y‐ metal ions

Coenzymes: small organic molecules

th ti ti htl b d‐ prosthetic group: tightly bound coenzyme ‐ loosely bound coenzyme: like substrate

Some enzymes requires cofactors

Holoenzyme = apoenzyme + cofactor

The cofactor may be:

1. A coenzyme ‐ a non‐protein organic substance which loosely interacts with apoenzyme.y p y

2. A prosthetic group ‐ an organic substance which is firmly h d hattached to the apoenzyme.

3 A metal‐ion‐activator ‐ these include K+ Fe2+ Fe3+ Cu2+3. A metal‐ion‐activator ‐ these include K , Fe , Fe , Cu , Co2+, Zn2+, Mn2+, Mg2+, Ca2+,and Mo3+

Some enzymes requires cofactors

Allosteric enzymes

Possess additional binding sites.

Multimeric proteins.

Regulatory enzymes, that are reversibly inhibited or activated by metabolites.

Isoenzymes:

• They are "multiple enzyme forms" of an enzyme that

y

• They are multiple enzyme forms of an enzyme that

catalyze the same reaction but differ in their structure.

• They have different kinetic parameters (e.g. different Km

values) and different regulatory properties.

Isoenzymes

Th li i i l i f bi i

y

• They are oligomeric proteins resulting from combination

of subunits..

• Isozymes are of wide clinical application e.g., lactate

dehydrogenase (LDH), creatine kinase (CK) and alkaline

h hphosphatase.

IsoenzymesLactate dehydrogenase isoforms:

y

Isoenzymes

• LDH1 is found in the heart and LDH5 is predominant in

y

• LDH1 is found in the heart and LDH5 is predominant in

the liver.

f l h d f d l f• LDH1 is useful in the diagnosis of myocardial infarction

and LDH5 in liver disease.

enzymes 2012

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