Transketolase

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Transketolase transketolase is an enzyme that plays an important role in the pentose phosphate cycle and the photosynthetic reduced pentose phosphate cycle. It is widely found in bacteria, yeast, spinach and liver. Crystals have been obtained. With thiamine pyrophosphate and Mg⁺⁺ as prosthetic groups.

Structure

The entrance to the active site of the enzyme is mainly composed of several arginine, histidine, serine and aspartic acid side chains, and the glutamic acid side chain plays a secondary role. These side chains, especially Arg359, Arg528, His469 and Ser386, are conserved in each transketolase and interact with the phosphate groups of the donor and acceptor substrates. Because the substrate channel is too narrow, the donor and acceptor substrates cannot be combined at the same time. Likewise, the substrate will be slightly extended when bound to the active site to accommodate this narrow channel. Although this enzyme can bind to many types of substrates, such as phosphorylated and non-phosphorylated monosaccharides, including ketones and aldoses, fructose, ribose, etc., it is highly specific to the three-dimensional configuration of sugar hydroxyl groups. These hydroxyl groups at C-3 and C-4 of the ketose donor must be in the D-threo configuration in order to correctly correspond to the C-1 and C-2 positions on the aldose acceptor. They also stabilize the substrate at the active site by interacting with Asp477, His30 and His263 residues. Therefore, the destruction of this configuration, whether it is the placement of the hydroxyl group or its stereochemistry, will change the H bond between the residue and the substrate, resulting in a decrease in the affinity to the substrate.

Function

The function of this enzyme is to transfer the ketol group (Ketol) on the ketose phosphate to the aldose phosphate. Because the broken molecules and the molecules formed by the combination also have ketol groups, it is called transketolase. Xylulose 5-phosphate, sedum heptulose 7-phosphate, fructose 6-phosphate, etc. are all substances that play an important role in biochemistry as ketol-based donors. All sugars must have 3 and 4 OH groups shown are arranged. In addition, xylulose, erythrulose, hydroxypyruvate, etc. can also be used as ketol group donors, but the reactivity is lower than the above-mentioned phosphoric acid compounds. As ethanol ketone acceptor substances, there are glyceraldehyde 3-phosphate, erythrose 4-phosphate, ribose 5-phosphate, and glycolaldehyde. Except for those based on hydroxypyruvate. Generally speaking, these reactions are reversible.

Mechanism

Transketolase plays a central role in the Calvin cycle of plant photosynthesis. Its activity is the limiting factor for the maximum photosynthetic rate of plants. A small decrease in its activity can lead to a decline in plant growth speed and aromatics. Inhibition of amino acid and phenylalanine metabolites. Since TK plays a key role in plant photosynthesis, and the TK protein sequence and function of various plants are very similar, the study of TK is useful for improving plant photosynthetic efficiency and researching new herbicides All are of great significance. TK was first discovered in Saccharomyces cerevisiae, and then found to exist in bacteria, plants and animals. Therefore, it has attracted much attention. Many scholars have successively developed the physiological function and metabolic activity of the gene. According to the research of SCHENK, etc., TK catalyzes the reversible transfer of 2 carbon atom units from ketose phosphate to aldose phosphate, and promotes the reversible conversion between hexa-carbon, five-carbon, four-carbon and three-carbon sugars. In different organisms, the substrate specificity of TK is also different.

Role in disease

In the absence of thiamine, transketolase activity is reduced, which is usually caused by malnutrition. Thiamine deficiency is associated with several diseases, including beriberi and biotin-thiamine-responsive basal ganglia disease. In Wernicke-Korsakoff syndrome, although mutations cannot be proven, there are signs that only in people with reduced transketolase affinity for thiamine, thiamine deficiency can cause Wernicke-Korsakoff syndrome. In this way, the activity of transketolase is greatly hindered, and as a result, the entire pentose phosphate pathway is inhibited.