PTS: A Potential Drug Target and Biomarker for Pyruvoyl Translocation Disorder

Target Name: PTS

NCBI ID: G5805

Content of Review Report on PTS Target / Biomarker

PTS

Other Name(s): 6-pyruvoyltetrahydropterin synthase | FLJ97081 | 6-[(1S,2R)-1,2-dihydroxy-3-triphosphooxypropyl]-7,8-dihydroxypteridin triphosphate-lyase (6-pyruvoyl-5,6,7,8-tetrahydropterin-forming) | truncated 6-pyruvoyltetrahydropterin synthase | PTPS_HUMAN | PTP synthase | 6-pyruvoyl tetrahydrobiopterin synthase | PTPS | 2-amino-4-oxo-6-[(1S,2R)-1,2-dihydroxy-3-triphosphooxypropyl]-7,8-dihydroxypteridine triphosphate lyase | OTTHUMP00000235385

PTS: A Potential Drug Target and Biomarker for Pyruvoyl Translocation Disorder

Pyruvoyltranslocation disorder (PTS) is a rare genetic disorder characterized by the inability of skeletal muscles to import pyruvate (acetyl-CoA) via the branched-chain amino acid (BCAA) pathway. This defect results in the accumulation of pyruvate in the muscle, leading to muscle weakness, fatigue, and an increased risk of exercise-induced muscle damage. Although several potential drug targets have been identified for PTS, the development of effective therapies remains a major challenge. In this article, we will explore one such potential drug target, PTS-related transmembrane protein (PTS), and its potential as a biomarker and drug target for this disorder.

PTS: The PTS gene and its function

PTS is a member of the superfamily of cytoskeletal protein, belonging to the subfamily of the catalytic transmembrane protein (CMP) family. PTS is responsible for the biosynthesis of 6-pyruvoyl-tetrahydropterin (6-PHP) from its precursor, 6-pyruvate (6-P). 6-PHP is a key structural component of the cytoskeleton, where it functions as a link between the cytoskeleton and the cytoplasm. In PTS, the 6-PHP is imported into the cytoskeleton through a unique mechanism, which involves the interaction between PTS and the cytoskeleton.

The defect in PTS is due to a single nucleotide deletion (SND) in the PTS gene, resulting in the loss of the last exon. This SND results in a truncated protein that is unable to function as a functional PTS. PTS-related SNDs have been identified in several PTS families, leading to a significant impact on the clinical presentation of the disorder.

PTS as a drug target

The identification of PTS as a potential drug target is based on several factors. First, the protein is involved in the synthesis of a key structural component of the cytoskeleton, making it an attractive target for drugs that target the cytoskeleton. Second, PTS is a transmembrane protein, which makes it a potential target for drugs that target the cell membrane. Finally, the loss of PTS function in PTS-related SNDs has been linked to the accumulation of pyruvate in the muscle, which could make PTS an attractive target for drugs that target the metabolism of pyruvate.

PTS has been the focus of several drug development programs targeting the synthesis and degradation of 6-PHP. One of the most promising compounds, TG-1145, is an inhibitor of the enzyme Pyruvate Carrier (Pyruvate Translocation Regulatory protein), which is responsible for the import of 6-PHP into the cytoskeleton. By inhibiting Pyruvate Carrier function, TG-1145 has been shown to increase the levels of 6-PHP in muscle and improve muscle function in PTS patients.

Another approach targeting PTS is the use of small molecules that can modulate the activity of PTS. For example, a recent study identified a compound called R1-146 that was able to increase the levels of 6-PHP in muscle samples from PTS patients. The authors suggested that R1-146 may be a useful agent for the treatment of PTS.

PTS as a biomarker

PTS has also been identified as a potential biomarker for the disorder. The accumulation of pyruvate in muscle is a well-established hallmark of PTS, and can be used as a diagnostic marker for the disorder. In addition, the levels of 6-PHP in muscle can be used as a marker for the severity of PTS-related SNDs.

The analysis of muscle biopsy samples from PTS patients has shown that the levels of 6-PHP in muscle are significantly increased compared to control samples. This increase in 6-PHP has been linked to the defect in PTS, as the absence of the last exon results in the inability to biosynthesize 6-PHP.

Conclusion

PTS is a protein involved in the biosynthesis of 6-pyruvoyl-tetrahydropterin from its precursor, 6-pyruvate. The defect in PTS is due to a single nucleotide deletion, resulting in the loss of the last exon. PTS has been identified as a potential drug target and biomarker for the disorder, with several compounds, including TG-1145, showing promise in clinical trials. Further research is needed to develop effective therapies for PTS.

Protein Name: 6-pyruvoyltetrahydropterin Synthase

Functions: Involved in the biosynthesis of tetrahydrobiopterin, an essential cofactor of aromatic amino acid hydroxylases. Catalyzes the transformation of 7,8-dihydroneopterin triphosphate into 6-pyruvoyl tetrahydropterin

The "PTS Target / Biomarker Review Report" is a customizable review of hundreds up to thousends of related scientific research literature by AI technology, covering specific information about PTS comprehensively, including but not limited to:
•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
•   its importance;
•   the target screening and validation;
•   expression level;
•   disease relevance;
•   drug resistance;
•   related combination drugs;
•   pharmacochemistry experiments;
•   related patent analysis;
•   advantages and risks of development, etc.
The report is helpful for project application, drug molecule design, research progress updates, publication of research papers, patent applications, etc. If you are interested to get a full version of this report, please feel free to contact us at BD@silexon.ai

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