Cofactors

Question 1

Biotin

Answer 1

Biotin (vitamin H or B7) is a cofactor in the metabolism of fatty acids and its biological role is to react with HCO 3- in the presence of ATP to form an active carbon dioxide transfer agent.

Question 2

S - A D E N O S Y L M E T H I O N I N E ( S A M )

Answer 2

Biological role - it is the cofactor that introduces methyl groups to a range of
nucleophilic sites, mostly N, O, activated aromatic carbons and α- to C=O.

The reaction with SAM formally involves a nucleophilic displacement,
the transfer of the Me group to the substrate is an Sn2 type processes

if there is an electron donating group on the benzene ring, e.g.an ‘OH’
or and amine then SAM can transfer a methyl group to the orthoand paraposition.

Question 3

Enzymes that catalyse reversible hydride transfers

Answer 3

dehydrogenases.

two domains, one binds the substrate and the other binds the cofactor.

conformational changes to the enzyme the substrate and cofactor are brought
together into a reactive configuration for hydride transfer.

Question 4

N I C OT I N A M I D E A D E N I N E D I N U C L E OT I D E ( P H O S P H AT E )
[ N A D / N A D H O R N A D P / N A D P H ] R E D OX C O U P L E S ]

Answer 4

Biological role - mediators of biological oxidations and reductions

NAD/NADH – 2 phosphates
*NADP/NADPH – 3 phosphates

nicotinamide ring. This is the part of the
structure involved in the loss and gain of
Hydrogens.

When a substrate is oxidised, hydride (H- ) is transferred from the substrate to C-4 of the
nicotinamide ring of the cofactor [NAD(P) to NAD(P)H]

The process isstereospecific. In any particular redox process, only one of the two pro-chiral
hydrogens will be transferred

Question 5

Carbonyl carbon of thioester is more electrophilic than the carbonyl carbon of a normal ester
because

Answer 5

the efficiency of orbital overlap between sulphur and carbon in a thioester is less efficient than
orbital overlap between oxygen and carbon in a normal ester

thiol/thiolate is a better leaving group than alkoxide (pKa = 11 and 16
respectively)

Less resonance donation from the thiol

Question 6

AC E T Y L S C O E N Z YM E A ( A c S C o A )

Answer 6

Biological Role = it is the most important acyl transfer reagent in living organisms

acid chloride in the lab- too readily hydolysed in vivo

Activation 1:
It activates it towards nucleophilic attack at the carbonyl carbon with displacement of CoAS- .

Activation 2:
It activates the acyl species towards alkylation at the α- carbon – analogous to α-alkylation of an
activated carbonyl compound

Question 7

C O E N Z Y M E A ( C o A S H )

Answer 7

Biological Role = It reacts with acyl substrates to form reactive acyl-thioester species called
Acetyl S Coenzyme A (AcSCoA)

Question 8

ADENOSINE TRIPHOSPHATE (ATP)

Answer 8

Biological role – transfer monophosphate or diphosphate to an alcohol OH to activate it towards nucleophilic substitution and/or elimination (form an alkene)

(analogous to tosylate in lab)

Question 9

Cofactors

Answer 9

small organic non-protein molecules that behave as intermediates that carry chemical groups
between enzymes.

the source of reagents for carrying out the reactionsin vivo