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First published online December 2, 2005
Journal of Experimental Biology 208, 4561-4575 (2005)
Published by The Company of Biologists 2005
doi: 10.1242/jeb.01961

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Lactate – a signal coordinating cell and systemic function

Andrew Philp^1,*, Adam L. Macdonald^1,2 and Peter W. Watt¹

¹ Department of Sport and Exercise Sciences, Chelsea School Research Centre, Welkin Performance Laboratories, Eastbourne, BN20 7SP, UK
² School of Pharmacy and Biomolecular Sciences, Cockcroft Building, University of Brighton, Eastbourne, BN20 7SP, UK

View larger version (34K): [in a new window]   Fig. 1. The processes involved in the lactate shuttle hypothesis (Brooks, 1986). The pathway proposes that (1) glucose enters the cell, where it is sequentially broken down to pyruvate (2). Pyruvate enters the mitochondrion, allowing respiration to continue in the tricarboxylic acid (TCA) cycle (3). Lactate is subsequently formed via the lactate dehydrogenase (LDH) reaction (4) and is then exported from the cytosolic compartment via monocarboxylate transporter (MCT) transport (5), where it is redistributed to a variety of functional sites. Note the suggested presence of mitochondrial lactate dehydrogenase (mLDH) (6), which forms the construct of the intracellular shuttle system (7) (see text for description).

View larger version (24K): [in a new window]   Fig. 2. Interacting processes suggested to be involved with increased lactate accumulation during exercise.

View larger version (34K): [in a new window]   Fig. 3. The effect of artificially elevated lactate concentrations (lactate clamp) on metabolic processes. Increased circulatory lactate concentrations (1) result in lactate entering the cytosol, where it then enters the mitochondrion via MCT1 (2). Within the mitochondrion, lactate is converted to pyruvate via mLDH (3), which then progresses into the tricarboxylic acid (TCA) cycle (4). However, artificially raised cytosolic lactate concentrations (5) lead to suppression in glycolysis. Therefore, a resulting increase in H+ and NADH occurs, and acidosis inhibits phosphofructokinase (PFK) activity (6). This suppression finally results in reduced glycolytic activation and a reduction, or sparing, of glycogenolysis.

View larger version (30K): [in a new window]   Fig. 4. Potential roles for lactate signalling during exercise of increasing intensity. At the onset of exercise, elevated lactate concentrations signal increased ventilatory drive and vasodilation, whilst sparing glucose and glycogen stores. As exercise intensity moves to the moderate zone, the increase in lactate mimics hypoxic conditions and triggers a number of adaptive responses. In this zone, lactate may also be involved with the transition to carbohydrate metabolism by inhibiting lipolysis. At severe exercise intensities, lactate acts as a peripheral signal to indicate exercise stress, whilst also maintaining the integrity of the muscle. High levels of lactate signal severe exercise stress and exercise is terminated, possibly through a central governor mechanism. Abbreviations: La, lactate; BLa, blood lactate; PRO, lactate protection; Glu, glucose; FA, fatty acid; EP, epinephrine; NEP, nor-epinephrine; VENT, increased ventilatory drive; VASD, vasodilation; Wmax, maximal power output.