ATP & HISTIDINE INTERRELATIONSHIPS

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

H2C

HN C
NH
H2C
CHO
OC
NH
RP

CH2OP
O

NHCOCH2NH2
NH 2
N
C
C
N
CH
C
HC
N R -P
N

P-Ribosylglycinamide
CH2OP
O

GLYCINE

ADP

P-Ribosylamine

OP-O-P

Fumarate

N
H

PRPP

CH

H2N

C
C

H2 N
C

CH

C
N

Fumarate
CH

RP

CH

C
N

P OCH 2 C

R-P-O-P-O-P

OH
NH
N

CONH 2
C

CH 2

P OCH 2

RP
+
OCCH2CH2CH (NH3 ) COO-

Glutamine

NH 2
OC
C
NH

NH
CH

Histidinal
+
HC C CH2CH(NH3)CH2OH
N
NH
C
H

Histidinol

NH
CH

+
CH2CH(NH3)CH2OP

CH
C

C CH2COCH2O P

HC
N

H H
POCH2 C C
C
OH OH HN

Imidazole glycerol- P

RP

P-Ribosylformimino5-aminoimidazolecarboxamide

HC

P-Ribulosyl-5-formimino5-aminoimidazolecarboxamide
CH

HC

OH OH

+
CH2CH(NH3)CHO

R-P

P-Ribosyl-AMP

CH

H2 N

CH

OH

NH
HC

OH OH

N
OH

C N

P-Ribosyl-5-aminoimidazole-4-carboxamide

HC

NH

CH 2 O P
O

RP

H2N

RP
P-Ribosyl5-amino-4-imidazole
N-succinylcarboxamide

CH

C
HCO
NH

H2N

P-Ribosyl-ATP

HC

CH

HISTIDINE

HNCO

Fumarate

P-Ribosyl- 5-formamidoimidazole-4-carboxamide

HC

+
CH2CH(NH3)COO-

Inosine-P (IMP)
C

RP

-OOC.CH.CH2 COO-

Succinate

RP
O
C

CH
N

P-Ribosyl5-amino-4-imidazole
carboxylate

Aspartate

N
C

R-P-O-P-O-P

OH

H2N

CH 2 O P
O

RP

C
C

N
C

ATP

P-Ribosyl-P-O-P

HN
HC

CH
N

-OOC

Adenylosuccinate

NH 2
N
C
C
N
CH
C
HC
N R -P-O-P
N

NH
CH

-OOC.CH.CH 2 COONH
N
C
C
N
CH
HC
C
N
RP
N
O
C

P-Ribosyl- 5-amino-4-imidazole

HC

OH OH

HC
H 2N C

NH2

CH2OP
O

HC

RP

ADENOSINE-P
(AMP)

NH2

OH OH

NH

P-Ribosylformylglycinamidine

P-Ribosylformylglycinamide

OH OH

NH
CHO

C
H

NH

Imidazoleacetol- P

P Formatio
AT
n

Histidinol-P
PRPP
ATP
HISTIDINE

on

HI

TI

DIN

E For m

at

Histidine and Purines have a unique and fascinating interrelationship. They both originate from the same compound 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 RNAs (Ribozymes) are now known to be catalytic.
Is this a clue to a pre-historic RNA World responsible for catalysis before the evolution of the Protein World"?

c 2000 IUBMB