Enzymes-cofactors
Dr. Mamoun Ahram
Resources
• Biochemistry. 5th edition. Berg JM, Tymoczko JL, Stryer L. New
York: W H Freeman; 2002.
– 8.1.1 Many Enzymes Require Cofactors for Activity
• http://www.ncbi.nlm.nih.gov/books/NBK22380/
– Section 9.2 Making a Fast Reaction Faster: Carbonic
Anhydrases
• http://www.ncbi.nlm.nih.gov/books/NBK22599/
• The Medical Biochemistry Pages
– Introduction to Vitamins and Minerals
• http://themedicalbiochemistrypage.org/vitamins.php
Cofactors
• What are cofactors?
• What are coenzymes?
– When are coenzymes called prosthetic groups and
when are they cosubstrates?
Classification of cofactors
Cofactors
Small organic
molecules
Metals
Metalloproteins
Metalassociated
proteins
Coenzymes
cosubstrates
Apoenzymes vs. holoenzymes
Vitamin derivatives as cofactors
• What are vitamins?
• Why are they important?
• What are the two classes of vitamins?
Vitamin C
• Ascorbic acid
• Example: prolyl
hydroxylase
– synthesizes 4hydroxyproline
(collagen)
• An antioxidant
Thiamin (vitamin B1)
• Active form: thiamin pyrophosphate, TPP
Pyruvate dehydrogenase complex
• Decarboxylation of pyruvate into acetyl CoA by the
pyruvate dehydrogenase complex
α-ketoglutarate dehydrogenase
• Decarboxylation of α-ketoglutarate into succinyl CoA
by α-ketoglutarate dehydrogenase
Riboflavin (vitamin B2)
• The precursor for the coenzymes flavin adenine
mononucleotide (FMD) and flavin adenine
dinucleotide (FAD)
Flavoproteins
• Protiens that require FMN or FAD as cofactors
• Redox reactions
• FAD and FMN are prosthetic groups
Succinate dehydrogenase
•
Oxidation of succinate into fumarate by succinate
dehydrogenase
Pyruvate dehydrogenase complex
• FAD is a prosthetic group for the pyruvate
dehydrogenase complex
– It does not change in the overall reaction
Niacin (vitamin B3)
• Precursor of nicotinamide adenine dinucleotide
(NAD+) and nicotinamide adenine dinucleotide
phosphate (NADP+)
– Cofactors for numerous dehydrogenases
– Cosubstrates
Pantothenic acid (vitamin B5)
• Precursor of alanine and pantoic acid
• Synthesis of coenzyme A (CoA)
– Metabolism of carbohydrate, fats and proteins
Coenzyme A
• Coenzyme A transports acetyl groups from one
substrate to another
– via reactive thioester bond
Pyruvate dehydrogenase complex
• Decarboxylation of pyruvate into acetyl CoA by the
pyruvate dehydrogenase complex
Citrate synthase
• Condensation of acetyl CoA and oxaloacetate into
citrate by citrate synthase
Pyridoxal phosphate (vitamin B6)
• Pyridoxal, pyridoxamine and pyridoxine are
precursors of active form
• Metabolism of amino acids
Pyridoxine
Pyridoxal
Pyridoxamine
pyridoxal
phosphate
Aminotransferases
• All aminotransferases contain the prosthetic group
pyridoxal phosphate (PLP)
Examples
• Aspartate aminotransferase
• Alanine aminotransferase
Biotin
• Carboxylation reactions
Pyruvate carboxylase
• condensation of CO2 to pyruvate forming oxaloacetate
by pyruvate carboxylase
Acetyl CoA carboxylase
• Carboxylation of acetyl CoA to malonyl CoA by acetyl
CoA carboxylase initiating fatty acid synthesis
– Biotin is a prosthetic group
Cobalamin (vitamin B12)
• Composed of a tetrapyrrol ring
structure and a cobalt ion in the
center
• Two significant reactions
– linking fatty acid metabolism
to sugar metabolism by
rearranging methylmalonyl
CoA to succinyl CoA
– the formation of methionine
from homocysteine by
methylation
Folic acid
•
•
Reduced within cells to tetrahydrofolate (THF) by
dihydrofolate reductase (DHFR), an NADPH-requiring
enzyme
THF derivatives carry and transfer of one carbon units
during biosynthetic reactions, especially of nucleotides
Lipoic acid
• Not a dietary requirement in humans
– Not a vitamin
• A co-factor in pyruvate dehydrogenase and αketoglutarate dehydrogenase
Metals
Metal
Zn2+
Zn2+
Enzyme
Carbonic anhydrase
Carboxypeptidase
Mg2+
Se
Mn2+
Hexokinase
Glutathione peroxidase
Superoxide dismutase
Example
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