Transaldolase 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 ...

() of the non-oxidative phase of 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 ...

. In humans, transaldolase is encoded by the ''TALDO1''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. The following chemical reaction is catalyzed by transaldolase: :

sedoheptulose 7-phosphate Sedoheptulose 7-phosphate is an intermediate in the pentose phosphate pathway. It is formed by transketolase and acted upon by transaldolase. Sedoheptulokinase is an enzyme that uses sedoheptulose and ATP to produce ADP and sedoheptulose 7-phosp ...

glyceraldehyde 3-phosphate Glyceraldehyde 3-phosphate, also known as triose phosphate or 3-phosphoglyceraldehyde and abbreviated as G3P, GA3P, GADP, GAP, TP, GALP or PGAL, is a metabolite that occurs as an intermediate in several central pathways of all organisms.Nelson, D ...

\rightleftharpoons

erythrose 4-phosphate Erythrose 4-phosphate is a phosphate of the simple sugar erythrose. It is an intermediate in the pentose phosphate pathway and the Calvin cycle. In addition, it serves as a precursor in the biosynthesis of the aromatic amino acids tyrosine, pheny ...

fructose 6-phosphate Fructose 6-phosphate (sometimes called the Neuberg ester) is a derivative of fructose, which has been phosphorylated at the 6-hydroxy group. It is one of several possible fructosephosphates. The β-D-form of this compound is very common in cells ...

Clinical significance

The pentose phosphate pathway has two metabolic functions: (1) generation of nicotinamide adenine dinucleotide phosphate (reduced

NADPH 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 NAD ...

), for reductive biosynthesis, and (2) formation of

ribose Ribose is a simple sugar and carbohydrate with molecular formula C5H10O5 and the linear-form composition H−(C=O)−(CHOH)4−H. The naturally-occurring form, , is a component of the ribonucleotides from which RNA is built, and so this compo ...

, which is an essential component of ATP, DNA, and

RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...

. Transaldolase links the pentose phosphate pathway to

glycolysis Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH ...

. In patients with deficiency of transaldolase, there's an accumulation of

erythritol Erythritol is an organic compound, a four-carbon sugar alcohol (or polyol) with no optical activity, used as a food additive and sugar substitute. It is naturally occurring. It can be made from corn using enzymes and fermentation. Its formula i ...

(from

), D-

arabitol Arabitol, or arabinitol, is a sugar alcohol. It can be formed by the reduction of either arabinose or lyxose. Some organic acid tests check for the presence of D-arabitol, which may indicate overgrowth of intestinal microbes such as ''Candida a ...

, and

ribitol Ribitol, or adonitol, is a crystalline pentose alcohol (C5H12O5) formed by the reduction of ribose. It occurs naturally in the plant '' Adonis vernalis'' as well as in the cell walls of some Gram-positive bacteria, in the form of ribitol phosp ...

. The deletion in 3 base pairs in the ''TALDO1'' gene results in the absence of serine at position 171 of the transaldolase protein, which is part of a highly conserved region, suggesting that the mutation causes the transaldolase deficiency that is found in

erythrocyte Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...

s and

lymphoblast __NOTOC__ A lymphoblast is a modified naive lymphocyte with altered cell morphology. It occurs when the lymphocyte is activated by an antigen (from antigen-presenting cells) and increased in volume by nucleus and cytoplasm growth as well as new mRN ...

s. The deletion of this amino acid can lead to

liver cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...

and

hepatosplenomegaly Hepatosplenomegaly (commonly abbreviated HSM) is the simultaneous enlargement of both the liver (hepatomegaly) and the spleen (splenomegaly). Hepatosplenomegaly can occur as the result of acute viral hepatitis, infectious mononucleosis, and hist ...

(enlarged spleen and liver) during early infancy. Transaldolase is also a target of

autoimmunity In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". ...

in patients with

multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...

Structure

Transaldolase is a single domain composed of 337 amino acids. The core structure is an α/β barrel, similar to other class I aldolases, made up of eight parallel

β-sheets 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 ...

and seven

α-helices 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 ear ...

. There are also seven additional α-helices that are not part of the barrel. Hydrophobic amino acids are located between the β-sheets in the barrel and the surrounding α-helices to contribute to packing, such as the area containing Leu-168, Phe-170, Phe-189, Gly-311, and Phe-315. In the crystal, human transaldolase forms a dimer, with the two subunits connected by 18 residues in each subunit. See mechanism to the left for details. The active site, located in the center of the barrel, contains three key residues: lysine-142, glutamate-106, and aspartate-27. The lysine holds the sugar in place while the glutamate and aspartate act as proton donors and acceptors.;

Mechanism of catalysis

The residue of lysine-142 in the active site of transaldolase forms a

Schiff base In organic chemistry, a Schiff base (named after Hugo Schiff) is a compound with the general structure ( = alkyl or aryl, but not hydrogen). They can be considered a sub-class of imines, being either secondary ketimines or secondary aldimine ...

with the keto group in

sedoheptulose-7-phosphate Sedoheptulose 7-phosphate is an intermediate in the pentose phosphate pathway. It is formed by transketolase and acted upon by transaldolase. Sedoheptulokinase is an enzyme that uses sedoheptulose and ATP to produce ADP and sedoheptulose 7-phos ...

after deprotonation by another active site residue, glutamate-106. The reaction mechanism is similar to the reverse reaction catalyzed by

aldolase Fructose-bisphosphate aldolase (), often just aldolase, is an enzyme catalyzing a reversible reaction that splits the aldol, fructose 1,6-bisphosphate, into the triose phosphates dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phospha ...

: The bond joining carbons 3 and 4 is broken, leaving

dihydroxyacetone Dihydroxyacetone (; DHA), also known as glycerone, is a simple saccharide (a triose) with formula . DHA is primarily used as an ingredient in sunless tanning products. It is often derived from plant sources such as sugar beets and sugar cane, an ...

joined to the enzyme via a Schiff base. This cleavage reaction generates the unusual aldose sugar

erythrose-4-phosphate Erythrose 4-phosphate is a phosphate of the simple sugar erythrose. It is an intermediate in the pentose phosphate pathway and the Calvin cycle. In addition, it serves as a precursor in the biosynthesis of the aromatic amino acids tyrosine, pheny ...

. Then transaldolase catalyzes the condensation of

glyceraldehyde-3-phosphate Glyceraldehyde 3-phosphate, also known as triose phosphate or 3-phosphoglyceraldehyde and abbreviated as G3P, GA3P, GADP, GAP, TP, GALP or PGAL, is a metabolite that occurs as an intermediate in several central metabolic pathway, pathways of all o ...

with the Schiff base of

, yielding enzyme-bound

. Hydrolysis of the Schiff base liberates free

, one of the products of the pentose phosphate pathway.

References

External links

* {{Portal bar, Biology, border=no EC 2.2.1

Clinical significance

Structure

Mechanism of catalysis

See also

References

External links