Glutamine Metabolism: Molecular Regulation, Biological Functions, and Diseases
Mudasir A. Kumar,
Sana Khurshid Baba,
Inamu Rashid Khan,
Mohd Shahnawaz Khan,
Fohad Mabood Husain,
Saheem Ahmad,
Mohammad Haris,
Mayank Singh,
Ammira S. Al-Shabeeb Akil,
Muzafar A. Macha,
Ajaz A. Bhat,
Mudasir A. Kumar
Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Kashmir, India
Search for more papers by this authorSana Khurshid Baba
Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Kashmir, India
Search for more papers by this authorInamu Rashid Khan
Department of Zoology, School of Life Sciences, Central University of Kashmir, Ganderbal, India
Search for more papers by this authorMohd Shahnawaz Khan
Department of Biochemistry, College of Sciences, King Saud University, Riyadh, Saudi Arabia
Search for more papers by this authorFohad Mabood Husain
Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University, Riyadh, Saudi Arabia
Search for more papers by this authorSaheem Ahmad
Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Hail, Hail City, Saudi Arabia
Search for more papers by this authorMohammad Haris
Center for Advanced Metabolic Imaging in Precision Medicine, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
Laboratory Animal Research Centre, Qatar University, Doha, Qatar
Search for more papers by this authorMayank Singh
Department of Medical Oncology (Lab.), Dr. BRAIRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, India
Search for more papers by this authorAmmira S. Al-Shabeeb Akil
Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha, Qatar
Search for more papers by this authorCorresponding Author
Muzafar A. Macha
Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Kashmir, India
Correspondence
Ajaz A. Bhat, Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha, Qatar.
Email: [email protected]
Muzafar A. Macha, Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology (IUST), Awantipora, Kashmir 192122, India.
Email: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Ajaz A. Bhat
Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha, Qatar
Correspondence
Ajaz A. Bhat, Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha, Qatar.
Email: [email protected]
Muzafar A. Macha, Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology (IUST), Awantipora, Kashmir 192122, India.
Email: [email protected]; [email protected]
Search for more papers by this authorMudasir A. Kumar,
Sana Khurshid Baba,
Inamu Rashid Khan,
Mohd Shahnawaz Khan,
Fohad Mabood Husain,
Saheem Ahmad,
Mohammad Haris,
Mayank Singh,
Ammira S. Al-Shabeeb Akil,
Muzafar A. Macha,
Ajaz A. Bhat,
Mudasir A. Kumar
Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Kashmir, India
Search for more papers by this authorSana Khurshid Baba
Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Kashmir, India
Search for more papers by this authorInamu Rashid Khan
Department of Zoology, School of Life Sciences, Central University of Kashmir, Ganderbal, India
Search for more papers by this authorMohd Shahnawaz Khan
Department of Biochemistry, College of Sciences, King Saud University, Riyadh, Saudi Arabia
Search for more papers by this authorFohad Mabood Husain
Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University, Riyadh, Saudi Arabia
Search for more papers by this authorSaheem Ahmad
Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Hail, Hail City, Saudi Arabia
Search for more papers by this authorMohammad Haris
Center for Advanced Metabolic Imaging in Precision Medicine, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
Laboratory Animal Research Centre, Qatar University, Doha, Qatar
Search for more papers by this authorMayank Singh
Department of Medical Oncology (Lab.), Dr. BRAIRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, India
Search for more papers by this authorAmmira S. Al-Shabeeb Akil
Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha, Qatar
Search for more papers by this authorCorresponding Author
Muzafar A. Macha
Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Kashmir, India
Correspondence
Ajaz A. Bhat, Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha, Qatar.
Email: [email protected]
Muzafar A. Macha, Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology (IUST), Awantipora, Kashmir 192122, India.
Email: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Ajaz A. Bhat
Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha, Qatar
Correspondence
Ajaz A. Bhat, Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha, Qatar.
Email: [email protected]
Muzafar A. Macha, Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology (IUST), Awantipora, Kashmir 192122, India.
Email: [email protected]; [email protected]
Search for more papers by this authorMudasir A. Kumar, Sana Khurshid Baba and Inamu Rashid Khan contributed equally to this work.
Funding: This study was supported by the Ramalingaswami Re-entry Fellowship (Grant number: D.O. NO.BT/HRD/35/02/2006) from the Department of Biotechnology, Government of India, New Delhi; Core Research Grant (CRG/2021/003805) from Anusandhan National Research Foundation (ANRF), formally called Science and Engineering Research Board (SERB), Government of India, New Delhi; Research Grant (ID No. 2022–16465) from Indian Council of Medical Research (ICMR), Government of India; Central Council for Research in Unani Medicine (CCRUM), Ministry of Ayurveda, Yoga & Naturopathy, Unani, Siddha, and Homoeopathy (AYUSH) (TECH-21013/20/2024-CCRUM-HQ), Government of India; and J&K Science Technology and Innovation Council, Department of Science and Technology (DST) (JKST&IC/SRE/936-40), Government of J&K to Muzafar A. Macha. Promotion of University Research and Scientific Excellence (PURSE) (SR/PURSE/2022/121) grant from the Department of Science and Technology (DST), Government of India, New Delhi to the Islamic University of Science and Technology (IUST), Awantipora. Sidra Medicine Precision Program provides research funding to Ajaz A. Bhat (SDR400190) and Ammira S. Al-Shabeeb Akil (SDR400149).
ABSTRACT
Glutaminolysis, the metabolic process of converting glutamine into key intermediates, plays an essential role in cellular energy production, signaling, biosynthesis, and redox balance. Deregulation of glutamine metabolism significantly influences various pathological conditions, including cancers and metabolic and neurological diseases. Emerging evidence shows that long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and oncogenic alterations in glutamine transporters and enzymes enhance glutamine's role as an alternative energy source, supporting cell survival and proliferation under nutrient and oxygen deprivation conditions. To combat the pathogenic effects of altered glutamine metabolism, researchers are developing targeted inhibitors of key enzymes and transporters involved in glutaminolysis. By interfering with the mechanisms that support the growth of cancer cells, these inhibitors may be able to stop the growth of tumors and treat metabolic and neurological conditions. This review provides a comprehensive overview of existing inhibitors and ongoing clinical trials targeting glutamine metabolism, focusing on its potential as a cancer therapeutic strategy. Additionally, the role of lncRNAs and circRNAs in regulating glutamine metabolism is explored, revealing novel avenues for therapeutic intervention in cancer and other diseases.
Conflicts of Interest
The authors declare no conflicts of interest.
Open Research
Data Availability Statement
Not appliable.
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