Dr. John Schloss to Give Invited Lecture
By Brent Davis
Dr. Schloss was invited to speak at the International Symposium on Brain Function/Dysfunction and Intervention, on December 16, 2024, at the Charles E. Schmidt College of Medicine, Florida Atlantic University. This symposium was in honor of Dr. Jang-Yen Wu.
Research Synopsis:
Title: Discovery of Unexpected Oxygen-Consuming Reactions and the Role They Play in Toxicity: Yesterday and Today
Biochemists were stunned 53 years ago when Bowes and Ogren1 discovered that the enzyme fixing CO2 in photosynthetic organisms also consumed O2 in a reaction that accounted for photorespiration. Most surprisingly, the same enzyme catalyzing the carboxylase reaction conducted the oxygenase reaction without cofactors commonly associated with O2-dependent reactions. Almost 20 years later, Schloss and Abell2 discovered that several different classes of metal-dependent aldolases,2,3 thiamine pyrophosphate (TPP)-dependent (peracid producing) decarboxylases,2 and pyridoxal phosphate (PLP)-dependent amino acid decarboxylases2,4 also had previously undetected oxygen-consuming side reactions devoid of the normal oxygenase cofactors. Subsequently, Schloss, Wu, and colleagues provided evidence that the human glutamate decarboxylases (and possibly cysteine sulfinic acid decarboxylases) were responsible for oxygen-induced seizures.5 A remaining question is whether the oxygen-consuming, peracid-producing TPP-dependent decarboxylases, pyruvate dehydrogenase and a-ketoglutarate dehydrogenase, play any role in reperfusion injury or mitochondrial dysfunction. Another long-standing mystery in pathophysiology is the mechanism by which cysteamine produces duodenal ulcers in the small intestine.6 Schloss and Szabo7 proposed that cysteamine’s ulcerogenic and anticancer effects are due to its interaction with the enzyme cysteamine dioxygenase (ADO). An oxygen-and cysteamine-dependent futile cycle of ADO is responsible for an enzyme-dependent (Type II) form of ferroptosis for those tissues catabolizing Coenzyme A.7 ADO is also responsible for producing hypotaurine as a biomarker for cancer.7
Ogren WL, Bowes G (1971) Ribulose diphosphate carboxylase regulates soybean photorespiration. Nat New Biol 230(13):159-60. https://doi.org/10.1038/newbio230159a0- Abell LM, Schloss JV (1991) Oxygenase side reactions of acetolactate synthase and other carbanion-forming enzymes Biochemistry 30(32):7883-7. https://doi.org/10.1021/bi00246a002
- Hixon M, Sinerius G, Schneider A, Walter C, Fessner WD, Schloss JV (1996) Quo vadis photorespiration: a tale of two aldolases. FEBS Lett 392(3):281-4. https://doi.org/10.1016/0014-5793(96)00830-7
- Bisello G, Longo C, Rossignoli G, Phillips RS, Bertoldi M (2020) Oxygen reactivity with pyridoxal 5′-phosphate enzymes: biochemical implications and functional relevance Amino Acids. 52(8):1089-1105. https://doi.org/10.1007/s00726-020-02885-6
- Davis K, Foos T, Wu J-Y, Schloss JV (2001) Oxygen-induced seizures and inhibition of human glutamate decarboxylase and porcine cysteine sulfinic acid decarboxylase by oxygen and nitric oxide. J Biomed Sci 8(4):359-64. https://doi.org/10.1007/BF02258378
- Selye H, Szabo S (1973) Experimental model for production of perforating duodenal ulcers by cysteamine in the rat. Nature 244(5416):458-9. https://doi.org/10.1038/244458a0
- Schloss JV, Szabo S (2024) On the origin of cysteamine-induced duodenal cytotoxicity and type II ferroptosis. Inflammopharmacology 32(6):3739-3744. https://doi.org/10.1007/s10787-024-01551-7