SORD

Fig1. Schematic graph of the SORD protein and published variants. (Mubalake Yilihamu, 2022)

What is SORD protein?

SORD gene (sorbitol dehydrogenase) is a protein coding gene which situated on the long arm of chromosome 15 at locus 15q21. Sorbitol dehydrogenase (SORD; EC 1.1.1.14) catalyzes the interconversion of polyols and their corresponding ketoses, and together with aldose reductase (ALDR1; MIM 103880), makes up the sorbitol pathway that is believed to play an important role in the development of diabetic complications. The first reaction of the pathway (also called the polyol pathway) is the reduction of glucose to sorbitol by ALDR1 with NADPH as the cofactor. SORD then oxidizes the sorbitol to fructose using NAD(+) cofactor. The SORD protein is consisted of 357 amino acids and its molecular mass is approximately 38.3 kDa.

What is the function of SORD protein?

SORD plays a crucial role in the polyol pathway, which is an alternate route for glucose metabolism. It functions as a polyol dehydrogenase that catalyzes the reversible NAD(+)-dependent oxidation of various sugar alcohols, such as D-sorbitol (D-glucitol), L-threitol, xylitol, and ribitol, leading to the respective C2-oxidized products like D-fructose, L-erythrulose, D-xylulose, and D-ribulose. Additionally, SORD may play a role in sperm motility by using sorbitol as an alternative energy source. Furthermore, SORD has been identified as a key enzyme in the polyol pathway and is associated with diseases like distal hereditary motor neuronopathy, indicating its importance in genetic research and potential therapeutic applications.

SORD Related Signaling Pathway

SORD protein is a key enzyme in the polyol pathway, which is an alternative route for glucose metabolism. This pathway is implicated in the etiology of diabetic complications such as diabetic neuropathy and retinopathy, induced by hyperglycemia. The polyol pathway involves the conversion of sorbitol to fructose, and SORD plays a central role in this conversion process. Additionally, SORD is involved in the metabolism of secondary alcohols and may have a broader role in cellular metabolism.

SORD Related Diseases

Sorbitol dehydrogenase encoded by SORD gene is a key metabolic enzyme involved in the polyol pathway and is associated with the occurrence and development of many diseases. Mutations in the SORD gene can lead to autosomal recessive diseases, As mentioned in Charcot-Marie-Tooth disease (CMT) and distal hereditary motor neuropathy (dHMN). Moreover, abnormalities in the SORD gene are associated with diabetic neuropathy, as the polyol pathway plays an important role in the pathogenesis of diabetic complications. Mutations in the SORD gene have also been linked to a number of other diseases, such as stroke, atherosclerosis, asthma, Schaf-Yang syndrome, depression, obesity, and type 2 diabetic retinopathy.

Bioapplications of SORD

Sorbitol dehydrogenase encoded by SORD gene has important application value in the field of medicine and drug development. As a drug target, SORD activity can be modulated by specific drugs, including Sulbutiamine, metformin (Dextanvelam), and others, which treat a variety of diseases including diabetes, malnutrition, systemic diseases, and tumors by inhibiting SORD activity. In addition, SORD has shown its importance as a biomarker in disease diagnosis and treatment monitoring. For example, by detecting SORD activity, the glucose metabolism status of patients can be assessed to assist in the diagnosis of diabetes. At the same time, SORD activity can also be used as a monitoring index of tumor treatment effect. In the diagnosis of neuropathy, MRI findings of the lower extremity muscles of patients with SORD-related diseases are also used to examine the distribution of fat accumulation, atrophy, and edema, providing potential clinical relevance.

Case Study 1: Wenlei Cao, 2009

Ssorbitol dehydrogenase (SORD) can convert sorbitol to fructose, which can then be metabolized via the glycolytic pathway in sperm to make ATP. Here we characterize Sord mRNA and SORD expression during mouse spermatogenesis and examine the ability of sorbitol to support epididymal sperm motility and tyrosine phosphorylation. Sord mRNA levels increased during the course of spermatogenic differentiation. SORD protein, however, was first detected at the condensing spermatid stage. By indirect immunofluorescence, SORD was present along the length of the flagella of caudal epididymal sperm. Furthermore, immunoelectron microscopy showed that SORD was associated with mitochondria and the plasma membranes of sperm. Sperm incubated with sorbitol maintained motility, indicating that sorbitol was utilized as an energy source.

Fig1. SORD is present in sperm but not in SDS-insoluble accessory structures of tails. A) Immunoblot probed with anti-SORD polyclonal antibody. B) Normal goat IgG. C) Anti-SORD polyclonal antibody.

Fig2. Immunoblot analysis of SORD (arrow) from pachytene spermatocytes (PS), round spermatids (RS), condensing spermatids (CS), and epididymal sperm (Sp).

Case Study 2: Zoltán Szabó, 2010

Sorbitol is an intermediate in the polyol pathway, which converts from glucose to fructose by sorbitol dehydrogenase (SORD). Androgens are essential for the development of prostate cancer. A putative androgen-responsive regulatory region at the SORD 5' promoter was identified using promoter deletion constructs in a luciferase reporter assay in COS-7 cells. Chromatin immunoprecipitation assay was used to assess the binding of androgen receptor to suggested androgen responsive regulatory region. Finally, the expression of SORD in the human prostate was evaluated in 29 prostate tissue samples by immunohistochemistry. The expression of SORD decreased after castration. Androgen supplementation to the LNCaP prostate cancer cell line led to a 7.5-fold increase in SORD mRNA expression. Furthermore, a chromatin immunoprecipitation assay proved that the androgen receptor can bind to this putative androgen-responsive regulatory region. Finally, the expression of SORD in the human prostate was localised to epithelial cells of both benign and malignant prostate tissue by immunohistochemistry.

Fig3. Response of SORD mRNA in LNCaP cells after treatment with 10 nM synthetic androgen R1881.

Fig4. SORD protein expression in the human prostate.

SORD has several biochemical functions, for example, D-xylulose reductase activity,L-iditol 2-dehydrogenase activity,NAD binding. Some of the functions are cooperated with other proteins, some of the functions could acted by SORD itself. We selected most functions SORD had, and list some proteins which have the same functions with SORD. You can find most of the proteins on our site.

SORD has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with SORD here. Most of them are supplied by our site. Hope this information will be useful for your research of SORD.

GH1;TNIK;RELA;MYH9;ANLN;PDLIM7;CFAP97