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Detection of Nail Oncometabolite SAICAR in Oral Cancer Patients and Its Molecular Interactions with PKM2 Enzyme
Rushikesh Patel1, Ajay Kumar Raj1, Kiran Bharat Lokhande2
1Cancer and Translational Research Lab, Dr. D. Y. Patil Biotechnology & Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune 411033, Maharashtra, India.
Abstract:
Oncometabolites are known to drive metabolic adaptations in oral cancer. Several oncometabolites are known to be shared between cancer cells and non-cancer cells including microbiotas to modulate the tumor microenvironment. Among potential oncometabolites, succinylaminoimidazolecarboxamide ribose5'-phosphate (SAICAR) supports the growth and invasiveness of cancer cells by pyruvate kinase M2 (PKM2) enzyme in a glucose starved tumor microenvironment. There is a significant gap that shows the detection of SAICAR in biological samples including nails of oral cancer patients. Metabolite identification of SAICAR was investigated in the nails of oral cancer patients using novel vertical tube gel electrophoresis (VTGE) and LC-HRMS. Further molecular docking and molecular dynamics simulations (MDS) were employed to determine the nature of molecular interactions of SAICAR (CHEBI ID:18319) with PKM2 (PDB ID: 4G1N). Molecular docking of SAICAR (CHEBI ID:18319) was performed against pyruvate kinase M2 (PDB ID: 4G1N). Data suggest the presence of oncometabolite SAICAR in nails of oral cancer. Molecular docking of SAICAR with PKM2 showed appreciable binding affinity (-8.0 kcal/mol) with residues including ASP407, THR405, GLU410, ARG443, GLY321, ARG436, HIS439, LYS266, and TYR466. Furthermore, MDS confirmed the specific binding of SAICAR within the activator site of PKM2 and the stability of SAICAR and PKM2 molecular interactions. In conclusion, SAICAR is a promising oncometabolite biomarker present in the nails of oral cancer patients. A significant activation potential of SAICAR exists with the PKM2 enzyme.
Insights
Succinylaminoimidazolecarboxamide ribose5'-phosphate (SAICAR), an oncometabolite, was detected in oral cancer patient nails. SAICAR interacts with pyruvate kinase M2 (PKM2), suggesting its potential as a novel oral cancer biomarker.
Area of Science:
- Biochemistry
- Oncology
- Metabolomics
Background:
- Oncometabolites drive metabolic adaptations in oral cancer, influencing the tumor microenvironment.
- Succinylaminoimidazolecarboxamide ribose5'-phosphate (SAICAR) is implicated in cancer cell growth and invasiveness, particularly in glucose-starved conditions.
- A knowledge gap exists regarding SAICAR detection in biological samples like oral cancer patient nails.
Purpose of the Study:
- To investigate the presence and role of SAICAR in oral cancer.
- To identify SAICAR in the nails of oral cancer patients.
- To elucidate the molecular interactions between SAICAR and pyruvate kinase M2 (PKM2).
Main Methods:
- Metabolite identification of SAICAR using novel vertical tube gel electrophoresis (VTGE) and LC-HRMS.
- Molecular docking and molecular dynamics simulations (MDS) to analyze SAICAR-PKM2 interactions.
- Analysis of SAICAR binding affinity and stability with PKM2.
Main Results:
- SAICAR was detected in the nails of oral cancer patients.
- Molecular docking revealed significant binding affinity (-8.0 kcal/mol) of SAICAR with key PKM2 residues.
- MDS confirmed stable binding of SAICAR within the PKM2 activator site.
Conclusions:
- SAICAR is a potential oncometabolite biomarker detectable in the nails of oral cancer patients.
- SAICAR exhibits significant activation potential with the PKM2 enzyme.
- This finding opens avenues for novel diagnostic strategies in oral cancer detection.
