O

O

O

O

O

OH

OH

OH

OH

NH

2

OH

OH

OH

OH

Fumarate

Fumarate

Aspartate

Imidazole glycerol- P

P-Ribosyl-ATP

carboxamide

carboxamide

5-aminoimidazole-

5-aminoimidazole-

P-Ribosyl-AMP

P-Ribulosyl-5-formimino-

C

C

NH

NH

2

C

CH

HC

N

N

N

N

+

+

+

+

+

+

+

H

OCH

2

C

C

H

OH

H

OH

C

H

C

C

OC

C

CH

HC

N

N

N

NH

H

OCH

2

OCH

2

C

C

H

OH

OH

C

CH

2

C

CONH

2

C

CH

HC

N

RP

RP

R-P-O-P-O-P

C

C

NH

2

C

CH

HC

N

N

N

N

R-P-O-P-O-P

C

C

NH

C

CH

HC

N

N

N

N

R-P

N

N

NH

H

C

C

H

OH

OH

CH

N

HN

C

C

Imidazole acetol- P

C

NH

N

C

H

HC

Histidinol-P

C

NH

N

C

HC

Histidinol

C

NH

N

C

HC

Histidinal

C

NH

N

C

HC

ADP

ADENOSINE-P

Adenylosuccinate

5-amino-4-imidazole

5-amino-4-imidazole

carboxylate

5-amino-4-imidazole

5-amino-

N-succinylcarboxamide

C

C

C

CH

RP

HC

N

NH

-OOC.CH.CH

COO-

2

N

N

N

C

C

C

O

CH

R P

HC

N

N

N

HN

C

C

O

CH

HCO

N

N

N

-OOC.CH.CH COO-

2

HNCO

C

CH

N

N

C

R P

H

(AMP)

Inosine-P

C

NH

N

C

HC

R P

R P

P

P

P

H

H

H

CH O

2

P

CH O

2

P

CH O

2

P

CH O

2

P

O

OP-O-P

H N

2

H N

2

C

C

C

CH

HC

N

N

N

N

R -P-O-P

NH

2

C

C

C

CH

HC

N

N

N

N

R -P

NH

2

H

H

CH CH(NH )COO-

2

3

CH CH(NH )CH OH

2

3

2

CH CH(NH )CH O

2

3

2

P

CH COCH O

2

2

P

CH CH(NH )CHO

2

3

C

C

C

C

CH

N

N

N

R P

H N

2

H

2

GLYCINE

O

OCCH2CH2CH COO

-

(NH3

+)

Glutamine

O

O

OH

OH

OH

OH

CH O

2

P

P-Ribosyl-P-O-P

P-Ribosyl-
glycinamide

formylglycinamide

P-Ribosylamine

formylglycinamidine

P-Ribosyl-

P-Ribosyl-

P-Ribosyl-

P-Ribosyl-

P-Ribosyl-

P-Ribosyl-

5-formamido-

P-Ribosyl-

PRPP

H2N

HISTIDINE

O

OH

NHCOCH NH

2

2

OH

CHO

HN

NH

RP

NH

OC

H C

2

H

C

2

CHO

NH

RP

NH

C

HC

CH

N

N

C

-OOC

C

CH

N

RP

N

C

RP

CH O

2

P

H N

2

H N

2

Succinate

imidazole-4-carboxamide

imidazole-4-carboxamide

ATP

(IMP)

*

Histidine and Purines have a unique and fascinating interrelationship. They both originate from the same compound ñ PRPP.
Both are characterised by the heterocyclic imidazole group. ATP is involved in the synthesis of histidine, not as a source of
energy but as the supplier of one each of its carbon and nitrogen atoms. One of the intermediary reactions ( ) involves the
splitting of the molecule into TWO imidazole compounds, one of which becomes the basis of the histidine molecule and the
other leads to the re-formation of the ATP - an ATP Cycle ! (Since this ATP

is involved in a cycle, de novo ATP must be

derived from PRPP in the conventional way shown in the top (purple) pathway

The imidazole component of the histidine molecule is often a major influence in the active site of an enzyme. Could the
imidazole component of purines have a similar catalytic activity? Some RNAís (Ribozymes) are now known to be catalytic.
Is this a clue to a pre-historic ìRNA Worldî responsible for catalysis before the evolution of the ìProtein World"?

ATP &

HISTIDINE

INTERRELATIONSHIPS

P-Ribosylformimino-

A CLUE TO PRE-HISTORIC "BIO"- CHEMISTRY ?

*

A

TP

Formatio

n

H

IS

TID

INE Form

at

io

n

PRPP

ATP

HISTIDINE

c

2000 IUBMB