6-Phosphogluconate dehydrogenase (6PGD) is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

in the

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

. It forms ribulose 5-phosphate from

6-phosphogluconate 6-Phosphogluconic acid (6-phosphogluconate) is an intermediate in the pentose phosphate pathway and the Entner–Doudoroff pathway. It is formed by 6-phosphogluconolactonase, and acted upon by phosphogluconate dehydrogenase to produce ribulo ...

: :6-phospho-D-gluconate + NAD(P)⁺

\rightleftharpoons

D-Ribulose 5-phosphate + CO2 + NAD(P)H + H⁺ It is an oxidative carboxylase that catalyses the decarboxylating reduction of

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 C6H12O6, and their molecular weight is 180.156 g/mol. Hexoses exist in two forms, open-chain or cyclic, that easily conver ...

mono-phosphate shunt and

s (PPP).

Prokaryotic A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Connec ...

and

eukaryotic Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bact ...

6PGD are

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

s of about 470

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...

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 called ...

s are

highly conserved In evolutionary biology, conserved sequences are identical or similar sequences in nucleic acids ( DNA and RNA) or proteins across species ( orthologous sequences), or within a genome ( paralogous sequences), or between donor and receptor taxa ( ...

. The protein is a

homodimer In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...

in which the

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

s act independently: each contains a large, mainly

alpha-helical The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues earli ...

domain Domain may refer to: Mathematics *Domain of a function, the set of input values for which the (total) function is defined ** Domain of definition of a partial function **Natural domain of a partial function **Domain of holomorphy of a function *Do ...

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 gen ...

. 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 (locomotion), the surface over which an organism lo ...

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 process by which inorganic carbon (particularly in the form of carbon dioxide) is converted to organic compounds by living organisms. The compounds are then used to store energy and as ...

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 6-phosphogluconate dehydrogenase (6PGD), a metabolic enzyme involved in the Pen ...

, 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 autosomes ...

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