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Chapter 7 (part 1)

Cofactors

Cofactors

Cofactors are organic or inorganic moleculesthat are required for the activity of a certainconjugated enzymes

Apoenzyme = enzyme (-) cofactor

Holoenzyme = enzyme (+) cofactor

Inorganic cofactors – essential ions

Organic cofactors – coenzymes

Metal ions can function aselectrophiles in active site

Zinc protease (angiotensin converting enzyme)

Coenzymes

Cosubstrates-

- altered in rxn and regenerated to originalstructure in subsequent rxn- disassociated from active site- shuttle chemical groups among differentenzyme rxns.

Prosthetic groups-

- remains bound to enzyme- must return to original form

Both cosubstrates and prosthetic groups supply

reactive groups not present on amino acid sidechains

Vitamin derived coenzymes

Must be obtained from diet

Synthesized by microorganisms andplants

Vitamin deficiencies lead to diseasestate

Most vitamins must be enzymaticallytransformed to function as acoenzyme

Vitamins

Vitamin

Coenzyme

Ascorbic acid (C)

not a coenzyme

Niacin

NAD(P)+/NAD(P)H

Riboflavin (B

2

FMN & FAD

Thiamin (B

1

Thiamin-pyrophosphate

Pyridoxal (B

6

Pyridoxal phosphate

Biotin

Biotin

Folate

Tetrahydrafolate

Cobalamin (B

12

adenosyl-and methylcobalamin

Vitamin A

Retinal

Vitamin K

Vitamin K

Pantothenate (B

3

Coenzyme A

Nicotinamide Coenzymes

N

C

O

OH

N

C

O

NH

2

NICOTINIC ACID

(NIACIN)

NICOTINAMIDE

N

C

O

NH

2

H

O

OH

OH

H

2 C

O PO

2

O PO

2

O

O

OH(OPO

3

)

OH CH

2

N

N

N N

NH

2

NICOTINAMIDE MONOPHOSPHATE ADENOSINE MONOPHOSPHATE

N

C

O

NH

2

H R

N

C

O

NH

2

H

R

H

OXIDIZED

REDUCED

NAD

+

/ NADP

+

Serve as cofactors in oxidation/reductionreactions

Act as co-substrates for dehydrogenases

Reduction of NAD

+

/NADP

+

and oxidation of

NADH/NADPH occurs 2 e- at a time.

Function in hydride ion transfer

Rxns forming NADH/NADPH are catabolic

NADH is coupled with ATP production inmitochondria

NADPH is an impt reducing agent inbiosynthetic reactions

Reduced forms (NADH/NADPH) absorb light at340 nm, oxidized forms (NAD

+

/NADP

+

) do not

Riboflavin (B2)

Water soluble vitamin

Severe deficiencies lead togrowth retardation,reproductive problems andneural degeneration

Meat, dairy products and darkgreen vegetables, legumes andgrains are good sources

FMN/FAD

Thiamin

Thiamin is the first Vitamin discovered (Vital amine = Vitamin) •

Deficiencies lead to disease called Beriberi (neurological disorders, heart problems, anorexia) •

Beriberi prevealent in undeveloped countries where polished grains make up the majority of the diet. •

Associated with alcohol related disorders (Wernickes-Korskofff syndrome – memory loss,unstable walk)

Thiamin pyrophosphate

Serves as a cofactor in decarboxylation rxn of keto acids •

Also functions as a prosthetic group in transketolases (catalyze the transfer of two carbonunits in carbohydrate metabolism)

Pyridoxal

N

HOH

2

C

H

2

C

O CH

3

H

OH

N

HOH

2

C

HC

O CH

3

H

O

N

HOH

2

C

H

2

C

O CH

3

H

NH

3

N

H

2

C

HC

O CH

3

H

O

O

O P O

O

N

H

2

C

H

2

C

O CH

3

H

NH

3

O

O P O

O

PYRIDOXINE

PYRIDOXAL

PRYIDOXAMINE

PYRIDOXAL 5' PHOSPHATE

PYRIDOXAMINE 5' PHOSPHATE

PYRIDOXAL-PHOSPHATE

C

R

O

H

NH

R

2

R

CH

N

R

2

• H2O+ H2O

ALDEHYDE

AMINE

SCHIFF BASE

•Important in amino acid metabolism•Bound to enzyme as a Schiff base thru rxn withlysine • PLP functions in transamination, decarboxylation,racemization, isomerization, side-chain eliminationrxns involving amino acids