Transcript Co Enzyme Lecture

Co-enzymes
and
cofactors
activity in enzymes
Many Enzymes Require
Cofactors for Activity

A cofactor is a small non-protein molecules
that is bound (either tightly or loosely) to an
enzyme and is required for catalysis.

Catalytic activity of many enzymes depends
on the presence of cofactors.
Many Enzymes Require
Cofactors for Activity
Types of cofactors
4
Essential Ion Cofactors

Activator ions – bind reversibly to enzyme and
often participate in substrate binding.

Metal ions of metalloenzymes – cations that are
tightly bound to enzyme and participate directly
in catalysis (Fe, Zn, Cu, Co).

Metal activated enzymes – require or are
stimulated by addition of metal ions (i.e. Mg2+, is
required by many ATP requiring enzymes)
inorganic cofactors
Functions of iron
 Iron must be present in hemoglobin in
order to pick oxygen
• Electron transport
• Oxygen binding
• Oxygen carrier
Examples of Iron-dependent Enzymes
Aldehyde Oxidase
R-CHO + O2  RCOOH + H-O-O-H
Tryptophan 5-monooxygenase
L-tyrptophan + BH4 + O2  5 OH L-tryptophan + BH2 + H2O
Fatty Acid desaturase
Stearoyl-CoA + NADH + H+ + O2  Oleoyl-CoA + NAD+ + 2H2O
Peroxidase
2H2O2  2H2O + O2
(O2 is either incorporated into the product or reduced by electrons)
Inorganic cofactors
Mg2 is used in glycolysis. In the first
step of converting glucose to glucose
6-phosphate
6 CH O H
2
5
O
H
4
ATP
H
OH
ADP
4
1
Mg
OH
OH
3
H
2+
OH
2
OH
glucose
5
H
H
H
6 CH O PO 2 
2
3
H ex okinase
O
H
OH
3
H
H
2
H
1
OH
OH
glucose -6-phosphate
Zinc Function

300 enzymes require zinc
◦ DNA, RNA polymerases

numerous hormones require zinc
◦ insulin
transcription factors (zinc finger proteins)
 membrane stability
 myelination
 skeletal development

Example of prosthetic group
Metalloenzymes
contain firmly
bound metal ions
at the enzyme
active sites
(examples: iron,
zinc, copper,
cobalt).
Example of
metalloenzyme: carbonic
anhydrase contains zinc
Ion
Examples of enzymes containing
this ion
Cupric
Cytochrome oxidase
Ferrous or Ferric
Cytochrome (via Heme)
Hydrogenase
Magnesium
Glucose 6-phosphatase
Hexokinase
Manganese
Arginase
Molybdenum
Nitrate reductase
Nitrogenase
Nickel
Urease
Zinc
Alcohol dehydrogenase
Carbonic anhydrase
Coenzyme

Coenzymes are small organic non-protein
molecules.

Loosely attached to apoenzymes, seperated
easily by dialysis they are often called
cosubstrate or secondary substrate.

Reaction involving:

oxidoreduction,

group. transfer,

Isomerization and

covalent bond formation req. coenzyme.
Coenzymes
•
Organic molecule that temporarily
binds to apoenzyme in order for it to work
+
apoenzyme
Protein
coenzyme
Non-Protein
holoenzyme
Total
The functional role of Coenzymes is to act
as transporters of chemical group

A coenzyme is a necessary helper for
enzymes that assist in biochemical
transformations.

These molecules act to transfer chemical
groups between enzymes or from Enzyme
to substrate or product.

A coenzyme Transport a variety of chemical
groups (Such as Hydride, Acetyl, Formyl,
Methenyl or methyl).
Vitamin Insufficiency Generally Result in
malfunction of enzymes

Main clinical symptoms of dietary vitamin
insufficiency generally arise due the
malfunction of enzymes.

Dietary vitamin insufficiency leads to a
lack of sufficient cofactors derived from
vitamins to maintain homeostasis.
Vitamins of B complex group acting as co-enzymes
vitamins
Thiamine Vitamin B 1
active form (co-enzyme)
TPP (thiamine pyrophosphate)
Riboflavin Vitamin B 2
FMN, FAD
Niacin Vitamin B 3
NAD,NADH
Pantothenic acid Vitamin component of coenzyme
B5
A
Pyridoxine Vitamin B 6
PLP (pyridoxal phosphate)
Biotin
Biotin
Folic acid
THF
Cobalamine Vitamin B 12
cobamide
(Tetrahydrofolate)
Vitamin B1 - Thiamine
 The active form is thiamin pyrophosphate (TPP)
 Thiamin is rapidly converted to thiamin
pyrophosphate (TPP) in small intestine, brain and
liver.
 TPP is formed from thiamin by the action of
thiamine diphosphotransferase.
TPP coenzyme is required by enzymes in the
decarboxylation of -keto acids.
 Entity Transferred; Aldehydes
TPP as co-enzymes
Riboflavin functions, vit B2
Active forms are
◦ Flavin adenine dinucleotide (FAD)
◦ Flavin mononucleotide (FMN)

These play key roles in hydrogen transfer
reactions associated with
◦ Glycolysis
◦ TCA cycle
◦ Oxidative phosphorylation.
21
Regulated by ACTH, aldosterone, and
thyroid hormone
p. 283b
p. 283c
FAD As co-enzyme
Vitamins and Derivatives Involved in
Group Transfer Reactions

Nicotine Adenine Dinucleotide (NAD) &
Nicotine Adenine Dinucleotide Phosphate
(NADP)

Derivative of Niacin (B3)

Serve as cofactors in oxidation / reduction
reactions

Act as co-substrates for dehydrogenases
◦ Entity Transferred; Hydride ion (H+ + 2e-)
Electron (Hydrogen atom)
(a reaction of glycolysis)
H+
glyceraldehyde 3P + NAD
(substrate)
(co substrate)
dehydrogenase
(enzyme )
•
•
DiPhosphoglyceric acid + NADH
(product)
(NAD act as
co-enzyme & H
acceptor)
 Coenzyme A
(CoA)
◦ Derivative of Pantothenic acid (B5)
◦ Entity Transferred; Acetyl group and
other acyl groups
Pyridoxal Phosphate
◦ PLP is Derivative of Pyridoxine (Vit. B6)
involved in :

Transamination reactions required for
the synthesis and catabolism of the amino acids.
◦ Decarboxylation reactions.

◦ Entity Transferred; Amino Groups(-NH2)
Example of co-enzyme in amino acid
metabolism
NH2

Glutamate + pyruvate + pyrodoxal P
(co-substrate,acceptor
Transaminase
& donor of amino group)
 (enzyme)
α-Ketoglutaric acid + Alanin

Biotin
is a coenzyme for enzymes that transfer carboxyl
groups
◦ Entity Transferred; Carbon Dioxide