Glucose-6-Phosphate Dehydrogenase

 

3D Image of G6PD:

 

Image borrowed from http://en.wikipedia.org/wiki/Image:G6PD.png

 

 

Brief Background

 

          Glucose-6-Phosphate Dehydrogenase (G6PD) is an enzyme involved in the first step of the pentose phosphate pathway, producing the 5-carbon sugar, ribose, for later nucleic acid synthesis and fatty acid synthesis. G6PD catalyzes the oxidation/reduction reaction from glucose-6-phosphate to 6-phophogluconate. This reaction pulls two electrons from G6P in order to reduce the coenzyme NADP+ to NADPH.

 

 

Reaction Mechanism of G6PD for the Pentose Phosphate pathway:

 

Image borrowed from http://en.wikipedia.org/wiki/Image:G6PD_mechanism.png

 

On a Molecular Level

 

The G6PD gene can be found on the chromosome Xq28 region. With 13 exons and 12 introns, the actual gene coding for G6PD is about 18,500 base pairs long. In its active form, it is made up of either two (dimer) or four (tetramer) identical subunits, each with a molecular mass of about 59-kilodaltons. Determined from cDNA sequencing, the primary structure contains 515 amino acids.

 

 

Comparison between G6PD from yeast and leuconostoc mesenteroides:

         

Several studies have been done comparing G6PD in humans, yeast, and leuconostoc mesenteroides. Below is a chart comparing data from yeast and L.mesenteroids. The molecular weight of G6PD in L.mesenteroids is about 104 Kd, and consists of two subunits of about 55 Kd. The G6PD in this species is unique in that it has no cysteine/cysteine residues and has an essential lysine at the active site. It also exhibits a dual coenzyme specificity, for both NAD+ and NADP+, while Yeast and most other types of G6PD only exhibit one, just NADP+.

 

 

 

Yeast

L.mesenteroids

Co-factors

NADP+

NAD+, NADP+

Optimum pH

9.2

7.0-8.5

Optimum Temperature

~55oC

~50oC

pI

6.1

4.6

Stability

Stable pH 5-11

Stable pH 6-9

Effectors

Mg2+

HCO-3

Inhibitors

Neucleoside

   monophosphates            Some nucleoside di-

   and triphosphates Myristic acid

Dihydroepiandrosterone

Palmitoyl-CoA

Phosphate   

ATP is a competitive

   Inhibiton

NADPH is competitive

   in the NAD+- dependent

   Reaction

 

 

 

Real World Application:

 

 

G6PD Deficiency Disorder

 

Deficiency in G6PD is a hereditary X-linked recessive disorder that mostly found in men, and frequently occurs in African Americans, Asians, and Mediterranean peoples. G6PD is found in red blood cells, and when G6PD in these erythrocytes cannot maintain NADPH levels, which in turn maintains glutathione levels, the red blood cells lose protection against oxidative damage. When oxidative stress occurs, red blood cells often rupture, leading to hemolytic anemia. Other clinical symptoms include neonatal jaundice leading to kernicterus, favism - or haemolysis after the ingestion of fava beans, and, in severe cases, chronic non-sphericytical haemoolytic anaemia.

This recessive disorder has stayed within the genotypes of humans most probably because the deficiency has been found to protect against a very lethal form of malaria.

 

 

 

To be continued, updated, and revised… ^__^

 

 

 

Sources:

 

1. http://rialto.com/g6pd/ G6PD deficiency homepage

2. www.cchi.com.hk/ specialtopic/case1/case1.htm

3. http://www.worthington-biochem.com/ZF/default.html

4. http://www.serva.de/products/knowledge/061334.shtml

5. http://www.answers.com/topic/glucose-6-phosphate-dehydrogenase-deficiency#copyright