6-Phosphogluconate dehydrogenase (6PGD) is an

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

in the

pentose phosphate pathway The pentose phosphate pathway (also called the phosphogluconate pathway and the hexose monophosphate shunt or HMP shunt) is a metabolic pathway parallel to glycolysis. It generates NADPH and pentoses (five-carbon sugars) as well as ribose 5-ph ...

. It forms ribulose 5-phosphate from 6-phosphogluconate: :6-phospho-D-gluconate + NAD(P)⁺

\rightleftharpoons

D-Ribulose 5-phosphate + CO2 + NAD(P)H + H⁺ It is an oxidative carboxylase that catalyses the oxidative decarboxylation of 6-phosphogluconate into ribulose 5-phosphate in the presence of NADP. This reaction is a component of the

hexose In chemistry, a hexose is a monosaccharide (simple sugar) with six carbon atoms. The chemical formula for all hexoses is , and their molecular weight is 180.156 g/mol. Hexoses exist in two forms, open-chain or cyclic, that easily convert into ...

mono-phosphate shunt and

s (PPP).

Prokaryotic A prokaryote (; less commonly spelled procaryote) is a single-celled organism whose cell lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Ancient Greek (), meaning 'before', and (), meaning 'nut' ...

and

eukaryotic The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...

6PGD are

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s of about 470

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

s whose

sequence In mathematics, a sequence is an enumerated collection of objects in which repetitions are allowed and order matters. Like a set, it contains members (also called ''elements'', or ''terms''). The number of elements (possibly infinite) is cal ...

s are highly conserved. The protein is a

homodimer In biochemistry, a protein dimer is a macromolecular complex or protein multimer, multimer formed by two protein monomers, or single proteins, which are usually Non-covalent interaction, non-covalently bound. Many macromolecules, such as proteins ...

in which the

monomer A monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or two- or three-dimensional network in a process called polymerization. Classification Chemis ...

s act independently: each contains a large, mainly alpha-helical domain and a smaller beta-alpha-beta domain, containing a mixed parallel and anti-parallel 6-stranded

beta sheet The beta sheet (β-sheet, also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gene ...

. NADP is bound in a cleft in the small domain, the

substrate Substrate may refer to: Physical layers *Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached ** Substrate (aquatic environment), the earthy material that exi ...

binding in an adjacent pocket.

Biotechnological significance

Recently, 6PGD was demonstrated to catalyze also the reverse reaction (i.e. reductive

carboxylation Carboxylation is a chemical reaction in which a carboxylic acid is produced by treating a substrate with carbon dioxide. The opposite reaction is decarboxylation. In chemistry, the term carbonation is sometimes used synonymously with carboxylation ...

) ''in vivo''. Experiments using ''Escherichia coli'' selection strains revealed that this reaction was efficient enough to support the formation of biomass based solely on CO₂ and pentose sugars. In the future, this property could be exploited for synthetic

carbon fixation Biological carbon fixation, or сarbon assimilation, is the Biological process, process by which living organisms convert Total inorganic carbon, inorganic carbon (particularly carbon dioxide, ) to Organic compound, organic compounds. These o ...

routes.

Clinical significance

Mutations within the gene coding this enzyme result in

6-phosphogluconate dehydrogenase deficiency 6-Phosphogluconate dehydrogenase deficiency (6PGD deficiency), or partial deficiency, is an autosomal hereditary disease characterized by abnormally low levels of Phosphogluconate dehydrogenase, 6-phosphogluconate dehydrogenase (6PGD), a metaboli ...

, an

autosomal An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosomal (sex chromosome) pairs, which may have different structures. The DNA in autosome ...

hereditary disease affecting the red blood cells.

As a possible drug target

6PGD is involved in cancer cell metabolism so 6PGD inhibitors have been sought.6-Phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumour growth by inhibiting LKB1–AMPK signalling. 2015
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Biotechnological significance

Clinical significance

As a possible drug target

See also

References

Further reading