Metabolismo Del Lactato 2008 ( Cajigal)

Current Trends in Lactate Metabolism: Introduction L. BRUCE GLADDEN Department of Kinesiology, Auburn University, Auburn, AL

ABSTRACT

muscles are placed in O2-rich environments, Laj disappears. Subsequently, Laj took center stage with the work of A.V. Hill (9) and the paradigm that Laj was the immediate energy donor for muscle contraction. A ‘‘revolution in muscle physiology’’ (10) occurred between 1926 and 1932 with the discoveries of both adenosine triphosphate (ATP) and phosphocreatine (PC); this period could be called the Phosphagen Era. Based on his own work and that of others, Lohmann (15–17) postulated that ATP hydrolysis was the immediate source of energy for muscle contraction and that PC was used to resynthesize ATP in the creatine kinase reaction (1). Direct evidence of ATP breakdown during contractions did not become available until about 30 yr later. Credit for this proof usually goes to Cain and Davies (5), who inhibited creatine kinase in muscles with the poison 1,fluoro-2,4dinitrobenzene (FDNB) and then immediately froze the muscles after a series of contractions. Under these conditions in which ATP resynthesis from PC was prevented, a decline in ATP concentration was observed. Notably, Lange (13) had reported similar results 7 yr earlier. The reason for the difficulty in obtaining absolute evidence of ATP hydrolysis in muscle contractions is the incredibly rapid kinetics of the creatine kinase reaction (1). Lardy`s group (12) calculated that all of the ATP in a rabbit skeletal muscle could be resynthesized from ADP and PC in only 30 ms (1), thus preventing detection of ATP breakdown unless the creatine kinase reaction were blocked. Given the association between Laj, O2, and fatigue (dating from Fletcher and Hopkins (7) and A.V. Hill (9)), and the removal of Laj from its eminent position as the immediate energy donor for muscle contraction, it is no

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s detailed by Brooks and me (4) in an historical review, the study of lactate (Laj) metabolism can be divided into several important time periods or eras. During the Pre-Lactate Era (~1780–1907), Scheele discovered Laj in sour milk in 1780 (14), and in 1808 Berzelius reported an elevated concentration of Laj ([Laj]) in ‘‘the muscles of hunted stags’’ (18). Several other notable studies were reported in the 1800s, including evidence that activity caused muscles to become acidic and that the amount of Laj increased with the amount of work done (4). In 1907, the Lactate Era (1907–1926) was ushered in by the classic studies of Fletcher and Hopkins (7). They (7) developed a method to prevent significant Laj formation in resting muscles before the extraction and analysis of the Laj. Accordingly, they were able to demonstrate that 1) freshly excised resting muscle contains only a small amount of Laj, 2) [Laj] increases in excised, resting, anaerobic muscles, 3) La j accumulates to high levels during stimulation of muscles to fatigue, and 4) when fatigued

Editor’s Note: This paper is an Editor-in-Chief–invited contribution from ACSM’s conference on Integrative Physiology of Exercise held in Indianapolis, Indiana, September 27–30, 2006. Address for correspondence: L. Bruce Gladden, Department of Kinesiology, 2050 Memorial Coliseum, Auburn University, Auburn, AL 368495323; E-mail: [email protected]. Submitted for publication June 2007. Accepted for publication September 2007. 0195-9131/08/4003-0475/0 MEDICINE & SCIENCE IN SPORTS & EXERCISEÒ Copyright Ó 2008 by the American College of Sports Medicine DOI: 10.1249/MSS.0b013e31816154c9

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BASIC SCIENCES

GLADDEN, L. B. Current Trends in Lactate Metabolism: Introduction. Med. Sci. Sports Exerc., Vol. 40, No. 3, pp. 475–476, 2008. In September 2006, at the Integrative Physiology of Exercise meeting in Indianapolis, IN, a symposium entitled ‘‘Current Trends in Lactate Metabolism’’ was presented. This short paper introduces two papers from that symposium. The first paper by L. Bruce Gladden briefly summarizes key pieces of evidence that support the cell-to-cell lactate shuttle, a concept that is no longer an hypothesis but that, instead, is now an established theory that provides the context for discussions of whole body metabolism. Gladden also offers a critical appraisal of the intracellular lactate shuttle and evaluates an ongoing controversy relative to the role of lactate in acid–base balance. In the second paper, Hashimoto and Brooks provide their evidence in support of the intracellular lactate shuttle and a lactate oxidation complex in the inner mitochondrial membrane. They also postulate that lactate is a cell-signaling molecule, ‘‘lactormone,’’ that can upregulate gene and protein expression. Both papers have been updated since their original presentations and represent the current state of knowledge. Key Words: LACTATE HISTORY, LACTATE SHUTTLE, CELL-TO-CELL LACTATE SHUTTLE, INTRACELLULAR LACTATE SHUTTLE, LACTATE OXIDATION COMPLEX, LACTIC ACIDOSIS

surprise that a long period following the 1930s could be called the Dead-End Waste Product Era from the perspective of Laj metabolism. Certainly, there was a great deal of research during this period including a flurry of activity surrounding the ‘‘anaerobic threshold,’’ a term coined by Wasserman and McIlroy (19) in 1964. In 1973, Wasserman, his colleague Whipp, and other coworkers refined the concept in their classic paper (20), which generated tremendous interest in the topic. Although contrary evidence was beginning to mount (6,11), in the minds of many, Laj was a detrimental by-product of high-intensity, O2-limited metabolism. As recounted in the first of two papers in this symposium, the prevailing view of Laj in metabolism underwent a sea

change following the introduction of what is now known as the cell-to-cell lactate shuttle by George Brooks in 1984 (2). In terms of Laj metabolism, we are presently in the midst of what could be called the Lactate Shuttle Era (8). In the first symposium paper, I briefly summarize the overwhelming case for the cell-to-cell lactate shuttle, offer a critical view of the more recently proposed intracellular lactate shuttle (3), and analyze an ongoing debate about lactic acidosis. In the second paper, Hashimoto and Brooks summarize their evidence for the intracellular lactate shuttle in skeletal muscle, and propose that Laj is also a cellsignaling molecule, ‘‘lactormone,’’ that can upregulate gene and protein expression.

BASIC SCIENCES

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Copyright @ 2008 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.