Journal of Stem Cell Research & Therapy

Two centuries of lactate- pyruvate confusion in cell metabolism: A need to put the anaerobic threshold to rest!

17^th World Congress on Tissue Engineering, Regenerative Medicine and Stem Cell Research & 10^th Global Conference on Physiotherapy, Physical Rehabilitation and Sports Medicine

October 28, 2022 | Webinar

Vadlakonda Lakshmipathi

Kakatiya University, India

Keynote: J Stem Cell Res Ther

Abstract:

Present models of intermediary metabolism (IM) project glucose under anaerobic conditions produces two pyruvate molecules, and aerobic oxidation of pyruvate to CO2 in mitochondrial tricarboxylic acid (TCA) cycle produces energy (ATP). Under defective respiratory function, pyruvate is presumed to be reduced to lactic acid to regenerate NAD+ to increase the flux of glucose for survival under anaerobic conditions. The discovery of lactate shuttles activating oxidative metabolism, and two mitochondrial pyruvate carrier proteins (MPC1 &MPC2) modulating pyruvate metabolism differently in the presence and absence of functional respiratory chain respectively raises several questions on IM. Both pyruvic acid and lactic acid were discovered in the middle of 18th century, but lactic acid remained the focus of research in 19th century. Pyruvate came into focus when Meyerhof and Lohman discovered phosphoenolpyruvate (PEP) in 1934, and Meyerhof et al (1938) reported that pyruvate kinase (PKM) in an irreversible reaction produces pyruvate and ATP as a terminal step in glycolysis. In response to Lardy and Zeigler’s demonstration (1945) that PKM reaction produces PEP but not pyruvate, Meyerhof and Oesper (1949) re-examined the equilibria of PK reaction and reported that PKM is a reversible reaction. The confusion on pyruvate-lactate functions in cells, however, remains. Present models of IM were developed based on in vitro studies, and putative assumptions, which ignored parallel reports and the respiratory functions of haemoglobin in vascular tissues. In this talk, I review four centuries of metabolic history and muscle function and suggest that while lactate is a product of anaerobic metabolism, lactate conversion to pyruvate activates regenerative oxidative metabolism. Keywords: Pyruvate, Lactate, Fermentation, Oxidative Metabolism, Lactate Shuttles, Mitochondrial Pyruvate Carrier Proteins, Peroxisomes, Apyrase/ENTPD4 (Ectonucleoside Triphosphate Diphosphohydrolase 4), Microenvironment.

Biography :

Vadlakonda Lakshmipathi has completed his PhD in 1982 from Kakatiya University, India. He has been the faculty of Kakatiya University from 1971 to 2006 (till his retirement) and after retirement he served as a Visiting Professor, University of Hyderabad a consultant scientist at Cell work Bangalore guest professor at NIPER Hyderabad and as adjunct professor at CRRAO (AIMS). He has 45 years of teaching experience, mainly in all areas of Cell Biology, Enzymology and Metabolic regulation. His focus after retirement for the past years is on cell signaling in cancer and diabetes.