7/31/2019 35 ATP - Histidine Interrelationships

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O

O

O

O

O

OH

OH

OH

OH

NH2

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-

CC

NH

NH 2

CCH

HCN

N

N

N

++

+++

+

+

H

OCH 2 C C

H

OH

H

OH

C

H

C C

OC

CCH

HCN

N

N

NH

H

OCH 2

OCH2

C C

H

OHOH

C CH 2C

CONH2

CCH

HCN

RP

RP

R-P-O-P-O-P

C

C

NH2

CCH

HCN

N

N

N

R-P-O-P-O-P

CC

NH

CCH

HCN

N

N

N

R-P

N

N

NH

H

C C

H

OHOH

CH

NHNC

C

Imidazoleacetol- P

C

NHNCH

HC

Histidinol-P

C

NHNC

HCHistidinol

C

NHNC

HC

Histidinal

CNHN

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

RPHC

N

NH

-OOC.CH.CH COO-2

N

N

N

CC

C

O

CH

RPHC

N

N

N

HN

CC

O

CHHCO

N

N

N

-OOC.CH.CH COO-2

HNCO CCH

N

N

C

RP

H

(AMP) Inosine-P

C

NHNC

HC

RPRP

PP

P

H

H

H

CH O2 P

CH O2 P

CH O2 P

CH O2 P

OOP-O-P

H N2

H N2

CC

C

CH

HCN

N

N

N

R -P-O-P

NH2

CC

C

CH

HCN

N

N

N

R -P

NH2

H

H

CHCH(NH)COO-2 3

CHCH(NH)CH OH2 3 2

CHCH(NH)CH O2 3 2 P

CHCOCHO2 2 P

CHCH(NH)CHO2 3

C

C

C

C

CH

N

N

N RP

H N2

H2

GLYCINE

O

OCCH2CH2CH COO-(NH3

+)

Glutamine

OO

OHOH OHOH

CH O2 P

P-Ribosyl-P-O-P

P-Ribosyl-glycinamide

formylglycinamide

P-Ribosylamine

formylglycinamidineP-Ribosyl-

P-Ribosyl-P-Ribosyl-

P-Ribosyl-

P-Ribosyl-

P-Ribosyl-

5-formamido-P-Ribosyl-

PRPP

H2N

HISTIDINE

O

OH

NHCOCHNH2 2

OH

CHO

HN

NHRP

NH

OC

H C2

H C2

CHO

NHRP

NH

C

HC CHN

N

C

-OOCC

CH

NRP

N

C

RP

CH O2 P

H N2

H N2

Succinate

imidazole-4-carboxamide

imidazole-4-carboxamide

ATP

(IMP)

ATP & HISTIDINE INTERRELATIONSHIPS

P-Ribosylformimino-

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

*

ATPFormation

HIST

IDINEFormatio

n

PRPP

ATP

HISTIDINE

Designed by Donald Nicholson c 2002 IUBMB

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 a supplier of one

each of its carbon and nitrogen atoms. One of the intermediary reactions ( ) involves the

splitting of the molecule into TWO imidazole fragments, one of which becomes the basis of the

histidine molecule while the other leads to the re-formation of the ATP - an ATP Cycle ! Since

this ATP feeds into a cycle, de novo ATP must be derived fron PRPP in the usual 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 activity? SomeRNAs (Ribozymes) are known to be catalytic. Is this a clue to a pre-historic "RNA World"

responsible for catalysis before the evolution of the "Protein World" ?

*