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BCMB 3100 ‐Introduction to Coenzymes & Vitamins
•Cofactors
• Essential ions
• Coenzymes
• Cosubstrates
• Prosthetic groups
•Coenzymes structure/function/active group
•Vitamins
Coenzymes
Apoenzyme + Cofactor Holoenzyme
(protein only) (active)
(inactive)
Some enzymes require _________ for activity
(1) _______________ (mostly metal ions)
(2) _____________ (organic compounds)
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Metal ions have diverse functionsin enzymes
• Participate in ____________, generally tightly bound to enzyme, function e.g. as electrophilic catalysts or aid in generating a nucleophile
• Participate in _________________ at the active site
Coenzymes
• Coenzymes act as group-transfer reagents
• Hydrogen, electrons, or other groups can be transferred
• Two types of coenzymes:
___________________
•
________________________
•See Appendix D in your text
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Types of cofactors
Ca++
K+
Mg++
Mn++
Fe-S centerzinc
coppercobalt
*ATP
* SAMUDP-sugar
* NAD+/NADP+
* tetrahydrofolate
* CoA
* ubiquinone protein coenzymes
* FMN/FAD
* TPP
* PLP
* Biotin
* adenosyl/methyl-cobalamin
* Lipoic acid/lipoamide
See:*Table 6.2 for example of enzymes that require metal or nonmetal cofactors*See pg. 144 regarding metal ions and catalysis*Tables 15.2 and 15.3 as summary tables for coenzymes
http://www.nd.edu/~aseriann/pyrde.html
The pyruvate dehydrogenase complex requires 5 coenzymes
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http://www.bioc.cam.ac.uk/uto/perham.html
Schematic model of 3D structure (bigger than a ribosome) of pyruvate dehydrogenase complex of Bacillus stearothermophilus. The E2 chain has 3 domains: lipoyl, peripheral subunit‐binding
and acetyltransferase. Active sites of E1, E2 and E3 are coupled by the swinging lipoyl domain. Only one trimer of icosahedral (60‐mer) E2 core is shown and only one E1(a2b2, lower) and one E3 (a2, upper) component is shown attached, for simplicity.
In Eukaryotes this complex has 102 subunits!! (30+60+12)!
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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
http://www.nd.edu/~aseriann/pyrde.html
The pyruvate dehydrogenase complex requires 5 coenzymes
E1 E2 E3
Cosubstrates
Prosthetic groups
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S‐Adenosylmethionine (SAM)
Activated methyl group in red
SAM is the donor of
methyl groups for most
biosynthetic reactions
One example of a cosubstrate coenzyme
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Example: SAM donates the methyl group for the synthesis of the hormone epinephrine from norepinephrine
S-Adenosylmethionine + X S-Adenosylhomocysteine + X-CH3
SAM SAHC
Phenylethanolamine N‐methyltransferase (PNMT)
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UDP‐sugar: activated form of sugars used as substrate in many biosynthetic reactions
Nucleotide-sugars are cosubstrates in many glycosylation reactions
A second example of a cosubstrate coenzyme
Fig. 15.4
A third example of a cosubstrate coenzyme
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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
These are noncoenzyme vitamins
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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
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Vitamin‐Derived Coenzymes
• Vitamins: (1) Essential organic compounds that the organism can not make but that are required for life.(2) Some vitamins are required for synthesis of some coenzymes. (3) Vitamins 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 DiseaseAscorbate (C) Scurvy
Nicotinic acid Pellagra
Riboflavin (B2) Growth retardation
Pantothenate (B3) Dermatitis in chickens
Thiamine (B1) Beriberi
Pyridoxal (B6) Dermatitis in rats
Biotin Dermatitis in humans
Folate Anemia, spina bifida
Cobalamin (B12) Pernicious anemia
(B3)
(B5)
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Vitamin C: a vitamin but not a coenzyme
• 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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You must learn to recognize the major coenzymes
Group Activity on Coenzymes
Be sure to read through “Hints for
learning coenzymes” as you prepare and
teach your coenzymes to your group.
Be sure to work in your groups to
learn the co-enzymesover the next week.
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Types of cofactors
Ca++
K+
Mg++
Mn++
Fe-S centerzinc
coppercobalt
*ATP
* SAMUDP-sugar
* NAD+/NADP+
* tetrahydrofolate
* CoA
* ubiquinone protein coenzymes
* FMN/FAD
* TPP
* PLP
* Biotin
* adenosyl/methyl-cobalamin
* Lipoic acid/lipoamide
See:*pg. 144 for info on metal ions in catalysis*Tables 15.2 and 15.3 as summary table for coenzymes
*
*ATP may also donate pyrophosphoryl and adenosyl groups or
adenylyl groups
2 electrons
1 or 2 electrons
1 or 2 electrons
2 carbon groupscontaining carbonyl
ATP‐dependent carboxylation
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2 carbon groupscontaining carbonyl
Fig. 15‐13
NAD+
_____________________
Nicotinamide adenine dinucleotide
NOTE: Electron carrier in many oxidation reduction
reactions; used for reactions in pathways that lead to generation of ATP
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Fig. 15.16
__________________
Nicotinamide adenine dinucleotide phosphate
NOTE: Electron donor in most reductive
biosynthesis reactions
Flavine adenine dinucleotide _______________
FAD
Fig. 15.14
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Fig. 15.14
FAD FADH2
Example of reduced substrate
Example of oxidized product
Pg. 296
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Fig. 15.18
Coenzyme A
Fig. 15.17
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Coenzyme A(carrying an acetyl group during a reaction)
Fig. 18.1
Pyridoxal phosphate
See pg. 636
Reactive site
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Tetrahydrofolate
Reactive sites
See pgs. 658‐659
See pgs. 365
Reactive site
Reactive site(s)
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cobalamin
See Appendix D
Reactive site
Ubiquinone(Coenzyme Q)
See Pg. 407
Reactive site(s)
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Group Activity on Coenzymes
Be sure to read through “Hints for
learning coenzymes” as you prepare and
teach your coenzymes to your group.
Be sure to work in your groups to
learn the co-enzymesover the next week.
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