Abstract: Various methods and compositions of treating 4-hydroxyphenylpyruvate dioxygenase-like (HPDL)-related diseases or disorders are presented herein. Also presented herein are methods of increasing CoQ10 biosynthesis, and methods of determining whether a subject will benefit from a CoQ10 or CoQ10 alternative treatment. Also presented herein are pharmaceutical compositions and dosage forms comprising 4-hydroxymandelic acid (4-HMA), and/or its metabolites. Further presented herein are compounds that inhibit 4-hydroxyphenylpyruvate dioxygenase-like (HPDL). Further presented herein are methods of identifying and/or assessing modulators of HPDL. Yet further presented herein are example methods and systems for isotopic labelling in cells by metabolizing cells in the presence of gaseous isotopic tracer.

Abstract: Various methods of treating cancer, autoimmune disease, or any disease involving cellular proliferation are presented herein comprising administering an effective amount of an HPDL inhibitor to the subject. The HPDL inhibitors used herein are ibuprofen, dopamine, or their derivatives. Also presented herein are methods of determining effectiveness of a treatment for cancer, autoimmune disease, or any disease involving cellular proliferation in a subject, comprising administering ibuprofen, dopamine, or their derivatives. Further presented herein are methods of predicting prognosis of cancer in a subject having cancer, autoimmune disease, or any disease involving cellular proliferation, wherein if the subject is determined to have poor prognosis, the method further comprising administering to the subject a single-agent chemotherapy, supportive care, and/or a compound that is ibuprofen, dopamine, or their derivatives.

Abstract: Various methods and compositions of treating 4-hydroxyphenylpyruvate dioxygenase-like (HPDL)-related diseases or disorders are presented herein. Also presented herein are methods of increasing CoQ10 biosynthesis, and methods of determining whether a subject will benefit from a CoQ10 or CoQ10 alternative treatment. Also presented herein are pharmaceutical compositions and dosage forms comprising 4-hydroxymandelic acid (4-HMA), and/or its metabolites. Further presented herein are compounds that inhibit 4-hydroxyphenylpyruvate dioxygenase-like (HPDL). Further presented herein are methods of identifying and/or assessing modulators of HPDL. Yet further presented herein are example methods and systems for isotopic labelling in cells by metabolizing cells in the presence of gaseous isotopic tracer.