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 substrates, and the enzyme converts the substrates into different molecules known as products. A ...
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-pho ...
. It forms
ribulose 5-phosphate
Ribulose 5-phosphate is one of the end-products of the pentose phosphate pathway. It is also an intermediate in the Calvin cycle
The Calvin cycle, light-independent reactions, bio synthetic phase, dark reactions, or photosynthetic carbon reducti ...
from
6-phosphogluconate:
:6-phospho-D-gluconate + NAD(P)
+ D-Ribulose 5-phosphate + CO2 + NAD(P)H + H
+
It is an oxidative carboxylase that
catalyses the decarboxylating
reduction of
6-phosphogluconate into
ribulose 5-phosphate
Ribulose 5-phosphate is one of the end-products of the pentose phosphate pathway. It is also an intermediate in the Calvin cycle
The Calvin cycle, light-independent reactions, bio synthetic phase, dark reactions, or photosynthetic carbon reducti ...
in the presence of
NADP
Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require N ...
. 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 convert ...
mono-phosphate shunt and
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-pho ...
s (PPP).
Prokaryotic
A prokaryote () is a Unicellular organism, single-celled organism that lacks a cell nucleus, nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek language, Greek wikt:πρό#Ancient Greek, πρό (, 'before') a ...
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. Bacte ...
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, respo ...
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 am ...
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 calle ...
s are
highly conserved.
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'' ha ...
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
Mo ...
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 e ...
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 g ...
.
NADP is bound in a cleft in the small domain, the
substrate 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 carboxylatio ...
) ''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 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 allosome, allosomal (sex chromosome) pairs, which may have different structures. The DNA in au ...
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
/ref>
See also
*Parietin
Parietin is the predominant cortical pigment of lichens in the genus ''Caloplaca'', a secondary product of the lichen ''Xanthoria parietina'', and a pigment found in the roots of Curled Dock (''Rumex crispus''). It has an orangy-yellow color and ...
, a 6PGD inhibitor
References
Further reading
*
{{1.1.1-enzyme-stub
NADPH-dependent enzymes
NADH-dependent enzymes
EC 1.1.1