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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

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*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.