Purine nucleotide cycle
Encyclopedia
The Purine Nucleotide Cycle is a metabolic pathway
in which fumarate is generated from aspartate in order to increase the concentration of Krebs cycle intermediates. The pathway was first described by John Lowenstein, who demonstrated its role in increasing the rate of oxidative phosphorylation
in skeletal muscle
.
reactions. The first stage is the deamination of the purine nucleotide
Adenosine monophosphate
(AMP) to form inosine monophosphate (IMP), catalysed by the enzyme AMP deaminase
:
The second stage is the formation of adenylosuccinate
from IMP and the amino acid aspartate, which is coupled to the energetically favourable hydrolysis of GTP
, and catalysed by the enzyme adenylosuccinate synthetase:
Finally, Adenylosuccinate is cleaved by the enzyme adenylosuccinate lyase
to release fumarate and regenerate the starting material of AMP:
Metabolic pathway
In biochemistry, metabolic pathways are series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by a series of chemical reactions. Enzymes catalyze these reactions, and often require dietary minerals, vitamins, and other cofactors in order to function...
in which fumarate is generated from aspartate in order to increase the concentration of Krebs cycle intermediates. The pathway was first described by John Lowenstein, who demonstrated its role in increasing the rate of oxidative phosphorylation
Oxidative phosphorylation
Oxidative phosphorylation is a metabolic pathway that uses energy released by the oxidation of nutrients to produce adenosine triphosphate . Although the many forms of life on earth use a range of different nutrients, almost all aerobic organisms carry out oxidative phosphorylation to produce ATP,...
in skeletal muscle
Skeletal muscle
Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...
.
Outline
The cycle is composed of three enzyme-catalysedEnzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
reactions. The first stage is the deamination of the purine nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
Adenosine monophosphate
Adenosine monophosphate
Adenosine monophosphate , also known as 5'-adenylic acid, is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid and the nucleoside adenosine. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine...
(AMP) to form inosine monophosphate (IMP), catalysed by the enzyme AMP deaminase
AMP deaminase
AMP deaminase 1 is an enzyme that in humans is encoded by the AMPD1 gene.Adenosine monophosphate deaminase is an enzyme that converts adenosine monophosphate to inosine monophosphate , freeing an ammonia molecule in the process.-Function:...
:
- AMP + H2O → IMP + NH4+
The second stage is the formation of adenylosuccinate
Adenylosuccinate
Adenylosuccinate is an intermediate in the intercoversion of purine nucleotides inosine monophosphate and adenosine monophosphate . The enzyme adenylosuccinate synthase carries out the reaction by the addition of aspartate to IMP and requires the input of energy from a phosphoanhydride bond in the...
from IMP and the amino acid aspartate, which is coupled to the energetically favourable hydrolysis of GTP
Guanosine triphosphate
Guanosine-5'-triphosphate is a purine nucleoside triphosphate. It can act as a substrate for the synthesis of RNA during the transcription process...
, and catalysed by the enzyme adenylosuccinate synthetase:
- Aspartate + IMP + GTP → Adenylosuccinate + GDPGuanosine diphosphateGuanosine diphosphate, abbreviated GDP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside guanosine. GDP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase guanine....
+ Pi
Finally, Adenylosuccinate is cleaved by the enzyme adenylosuccinate lyase
Adenylosuccinate lyase
Adenylosuccinate lyase is an enzyme that converts adenylosuccinate to AMP and fumarate as part of the purine nucleotide cycle....
to release fumarate and regenerate the starting material of AMP:
- Adenylosuccinate → AMP + Fumarate