Cofactors and Coenzymes
• Some enzymes do not need any additional
components to show full activity.
• However, others require non-protein
molecules called cofactors to be bound for
activity.
• Cofactors can be either inorganic (e.g., metal
ions and iron-sulfur clusters) or organic
compounds, (e.g., flavin and heme).
Cofactors
• Active enzyme / Holoenzyme:
– Polypeptide portion of enzyme (apoenzyme)
– Nonproteineous group (cofactor)
• Cofactors are bound to the enzyme for it to maintain
the correct configuration of the active site
– Metal ions
– Organic compounds
– Organometallic compounds
Organic cofactors can be either:
prosthetic groups, which are tightly bound to
an enzyme, or coenzymes, which are released
from the enzyme's active site during the
reaction.
carbonic anhydrase, with a zinc cofactor
bound as part of its active site. These tightlybound molecules are usually found in the
active site and are involved in catalysis.
For example, flavin and heme cofactors are often
involved in redox reactions.
Most cofactors are not covalently attached to an
enzyme, but are very tightly bound. However,
organic prosthetic groups can be covalently bound.
Coenzymes
Coenzymes are small organic molecules that
transport chemical groups in an enzymatic
reaction.
OR
Any of a number of freely diffusing organic
compounds that function as cofactors with
enzymes in promoting a variety of metabolic
reactions.
Some of these chemicals such as riboflavin,
thiamine and folic acid are vitamins, (acquired).
The chemical groups carried include the
hydride ion (H-) carried by NAD or NADP+, the
acetyl group carried by coenzyme A, … etc.
Since coenzymes are chemically changed as a
consequence of enzyme action, it is useful to
consider coenzymes to be a special class of
substrates, or second substrates, which are
common to many different enzymes.
About 700 enzymes are known to use the
coenzyme NADH.
Coenzymes are usually regenerated and their
concentrations maintained at a steady level
inside the cell: for example, NADPH is
regenerated through the pentose phosphate
pathway and S-adenosylmethionine by
methionine adenosyltransferase
Coenzymes participate in enzyme-mediated
catalysis in stoichiometric (mole-for-mole)
amounts and are modified during the
reaction.
Coenzymes
• A coenzyme is
required by some
enzymes
– An organic molecule
bound to the enzyme
by weak interactions /
Hydrogen bonds
– Most coenzymes carry
electrons or small
groups
– Many have modified
vitamins in their
structure
Nicotinamide Adenine Dinucleotide in
19.7 Cofactors and Coenzymes
Oxidized and Reduced Forms
NAD+ to NADH Mechanism
19.7 Cofactors and Coenzymes
• The nicotinamide part of NAD+ accepts a hydride
ion (H plus two electrons) from the alcohol to be
oxidized
• The alcohol loses a proton ( H+ ) to the solvent
H
+
N
R
O
C NH2
H
+
H O C R1
H
Oxidized form
HO
H
ox
red
C NH2
N
R
+
O C R1
H
+H+
Reduced form
19.7 Cofactors and Coenzymes
Two Other Adenine
Dinucleotide Coenzymes