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Coenzymes
BCMB 3100 ‐
Introduction to Coenzymes & Vitamins
Some enzymes require _________ for activity
•Cofactors
(1) _______________ (mostly metal ions)
•Essential ions
(2) _____________ (organic compounds)
•Coenzymes
•Cosubstrates
Apoenzyme + Cofactor
•Prosthetic groups
Holoenzyme
(protein only)
•Coenzymes structure/function/active
group
(active)
(inactive)
•Vitamins
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Metal ions have diverse functions
in enzymes
• Participate in ____________, generally tightly bound to enzyme, function e.g. as electrophilic catalysts or aid in generating a nucleophile
Coenzymes
• Coenzymes act as group-transfer reagents
• Hydrogen, electrons, or other groups can be
transferred
• Two types of coenzymes:
___________________
• Participate in _________________ at the active site •
________________________
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The pyruvate dehydrogenase complex
requires 4 coenzymes
Types of cofactors
Ca++
K+
Mg++
Mn++
Fe-S center
zinc
copper
cobalt
See:
*pg. 126 for info on metal ions in catalysis
*Table 15.2 (page 261) as summary table for
coenzymes
*ATP
* SAM
UDP-sugar
* FMN/FAD
* TPP
* PLP
* Biotin
* NAD+/NADP+
* tetrahydrofolate
* adenosyl/methyl* CoA
cobalamin
* ubiquinone
* Lipoic acid/
* protein coenzymes
lipoamide
http://www.nd.edu/~aseriann/pyrde.html
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Coenzyme Classification
• There are two classes of coenzymes
(1) ____________ are altered during the reaction
and regenerated by another enzyme
(2) _________________ remain bound to the
enzyme during the reaction, and may be
covalently or tightly bound to enzyme
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S‐Adenosylmethionine (SAM)
SAM is the
donor of
methyl groups
for most
biosynthetic
reactions
S-Adenosylmethionine + X  S-Adenosylhomocysteine + X-CH3
Activated methyl
group in red
Example: SAM donates the methyl group for the
synthesis of the hormone epinephrine from
norepinephrine
SAM
SAHC
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UDP‐sugar: activated form of sugars used as substrate in many biosynthetic reactions
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A third example of a cosubstrate coenzyme
Fig. 15.3
Nucleotide-sugars are cosubstrates in many glycosylation
reactions
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Some coenzymes require vitamins as part of their structure
__________: organic substance required in trace amounts for a number of essential biochemical reactions
Not all vitamins are part of coenzymes; only some are
Table 15‐4
Some vitamins are ___________
• Four lipid vitamins: A, D, E, K
• All contain rings and long, aliphatic side chains
• All are highly hydrophobic
• The lipid vitamins differ widely in their functions
Vitamin‐Derived Coenzymes
• Vitamins: required for synthesis of some coenzymes,
must be obtained from nutrients
• Animals rely on plants, meat, & microorganisms for
vitamin sources
• Most vitamins must be enzymatically transformed to
make the coenzyme (e.g. some water soluble
vitamins)
• BE SURE TO LEARN WHICH VITAMINS ARE
PART OF WHICH COENZYMES (Tables 15.2 & 15.3)
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Vitamins, nutritional deficiency diseases
(see Table 15.3 and Appendix D)
Vitamin C: a vitamin but not a coenzyme
Vitamin
Disease
Ascorbate (C)
Nicotinic acid (B3)
Riboflavin (B2)
Pantothenate (B53)
Thiamine (B1)
Pyridoxal (B6)
Biotin
Folate
Cobalamin (B12)
Scurvy
Pellagra
Growth retardation
Dermatitis in chickens
Beriberi
Dermatitis in rats
Dermatitis in humans
Anemia, spina bifida
Pernicious anemia
• A reducing reagent for hydroxylation of collagen
• Deficiency leads to the disease scurvy
• Most animals (not primates) can synthesize Vit C
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Group Activity on Coenzymes
Be sure to read through “Hints for
You must learn to recognize the major coenzymes
learning coenzymes” as you prepare and
teach your coenzymes to your group.
Be sure to work
in your groups to
learn the co-enzymes
over the next week.
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Types of cofactors
*
2 electrons
1 or 2 electrons
1 or 2 electrons
Ca++
K+
Mg++
Mn++
Fe-S center
zinc
copper
cobalt
See:
*pg. 126 for info on metal ions in
catalysis
*Table 15.2 as summary table for
coenzymes
*ATP
* SAM
UDP-sugar
2 carbon groups
containing carbonyl * FMN/FAD
* TPP
* PLP
* Biotin
* NAD+/NADP+
* tetrahydrofolate
* adenosyl/methyl* CoA
cobalamin
* ubiquinone
*
Lipoic acid/
protein coenzymes
ATP‐dependent carboxylation
*ATP may also donate pyrophosphoryl and adenosyl groups
lipoamide
NAD+
2 carbon groups
containing carbonyl NOTE: Electron carrier in many oxidation reduction reactions; used for reactions in pathways that lead to generation of ATP
Nicotinamide adenine dinucleotide
_____________________
Fig. 15‐12a
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Flavine adenine dinucleotide _______________
Nicotinamide adenine dinucleotide phosphate
__________________
FAD
NOTE: Electron donor in most reductive biosynthesis reactions
Fig. 15.15
Fig. 15.13
FAD
FADH2
Example of reduced substrate
Example of oxidized product
Fig. 15.14
Pg. 258
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Coenzyme A
Fig. 15.16
Fig. 15.17
Coenzyme A
Pyridoxal phosphate
(carrying an acetyl group during a reaction)
Fig. 18.1
See pg. 545
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cobalamin
See pgs. 319‐321
Ubiquinone
(Coenzyme Q)
See Appendix D
Group Activity on Coenzymes
Be sure to read through “Hints for
learning coenzymes” as you prepare and
teach your coenzymes to your group.
See Pg. 356
Be sure to work
in your groups to
learn the co-enzymes
over the next week.
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