The pulmonary O2 uptake (V̇o2p) response to ramp-incremental (RI) exercise increases linearly with work rate (WR) after an early exponential phase, implying that a single time constant (τ) and gain (G) describe the response. However, variability in τ and G of V̇o2p kinetics to different step increments in WR is documented. We hypothesized that the "linear" V̇o2p-WR relationship during RI exercise results from the conflation between WR-dependent changes in τ and G. Nine men performed three or four repeats of RI exercise (30 W/min) and two step-incremental protocols consisting of four 60-W increments beginning from 20 W or 50 W. During testing, breath-by-breath V̇o2p was measured by mass spectrometry and volume turbine. For each individual, the V̇o2p RI response was characterized with exponential functions containing either constant or variable τ and G values. A relationship between τ and G vs. WR was determined from the step-incremental protocols to derive the variable model parameters. τ and G increased from 21 ± 5 to 98 ± 20 s and from 8.7 ± 0.6 to 12.0 ± 1.9 ml·min(-1)·W(-1) for WRs of 20-230 W, respectively, and were best described by a second-order (τ) and a first-order (G) polynomial function of WR (lowest Akaike information criterion score). The sum of squared residuals was not different (P > 0.05) when the V̇o2p RI response was characterized with either the constant or variable models, indicating that they described the response equally well. Results suggest that τ and G increase progressively with WR during RI exercise. Importantly, these relationships may conflate to produce a linear V̇o2p-WR response, emphasizing the influence of metabolic heterogeneity in determining the apparent V̇o2p-WR relationship during RI exercise.

Mitochondrial pyruvate dehydrogenase (PDH) regulates the delivery of carbohydrate-derived substrate to the mitochondrial tricarboxylic acid cycle and electron transport chain. PDH activity at rest and its activation during exercise is attenuated following high-fat (HFAT) compared with high-carbohydrate (HCHO) diets. Given the reliance on carbohydrate-derived substrate early in transitions to exercise, this study examined the effects of HFAT and HCHO on phase II pulmonary O2 uptake (V̇o2 p) kinetics during transitions into the moderate-intensity (MOD) exercise domain. Eight active adult men underwent dietary manipulations consisting of 6 days of HFAT (73% fat, 22% protein, 5% carbohydrate) followed immediately by 6 days of HCHO (10% fat, 10% protein, 80% carbohydrate); each dietary phase was preceded by a glycogen depletion protocol. Participants performed three MOD transitions from a 20 W cycling baseline to work rate equivalent to 80% of estimated lactate threshold on days 5 and 6 of each diet. Steady-state V̇o2 p was greater (P < 0.05), and respiratory exchange ratio and carbohydrate oxidation rates were lower (P < 0.05) during HFAT. The phase II V̇o2 p time constant (τV̇o2 p) [HFAT 40 ± 16, HCHO 32 ± 19 s (mean ± SD)] and V̇o2 p gain (HFAT 10.3 ± 0.8, HCHO 9.4 ± 0.7 ml·min(-1·)W(-1)) were greater (P < 0.05) in HFAT. The overall adjustment (effective time constant) of muscle deoxygenation (Δ[HHb]) was not different between diets (HFAT 24 ± 4 s, HCHO 23 ± 4 s), which coupled with a slower τV̇o2 p, indicates a slowed microvascular blood flow response. These results suggest that the slower V̇o2 p kinetics associated with HFAT are consistent with inhibition and slower activation of PDH, a lower rate of pyruvate production, and/or attenuated microvascular blood flow and O2 delivery.

Love LK, LeBlanc PJ, Inglis JG, Bradley NS, Choptiany J, Heigenhauser GJ, Peters SJ. The relationship between human skeletal muscle pyruvate dehydrogenase phosphatase activity and muscle aerobic capacity. J Appl Physiol 111: 427-434, 2011. First published May 19, 2011 doi:10.1152/japplphysiol.00672.2010.-Pyruvate dehydrogenase (PDH) is a mitochondrial enzyme responsible for regulating the conversion of pyruvate to acetyl-CoA for use in the tricarboxylic acid cycle. PDH is regulated through phosphorylation and inactivation by PDH kinase (PDK) and dephosphorylation and activation by PDH phosphatase (PDP). The effect of endurance training on PDK in humans has been investigated; however, to date no study has examined the effect of endurance training on PDP in humans. Therefore, the purpose of this study was to examine differences in PDP activity and PDP1 protein content in human skeletal muscle across a range of muscle aerobic capacities. This association is important as higher PDP activity and protein content will allow for increased activation of PDH, and carbohydrate oxidation. The main findings of this study were that 1) PDP activity (r 2 ϭ 0.399, P ϭ 0.001) and PDP1 protein expression (r 2 ϭ 0.153, P ϭ 0.039) were positively correlated with citrate synthase (CS) activity as a marker for muscle aerobic capacity; 2) E1␣ (r 2 ϭ 0.310, P ϭ 0.002) and PDK2 protein (r 2 ϭ 0.229, P ϭ0.012) are positively correlated with muscle CS activity; and 3) although it is the most abundant isoform, PDP1 protein content only explained ϳ18% of the variance in PDP activity (r 2 ϭ 0.184, P ϭ 0.033). In addition, PDP1 in combination with E1␣ explained ϳ38% of the variance in PDP activity (r 2 ϭ 0.383, P ϭ 0.005), suggesting that there may be alternative regulatory mechanisms of this enzyme other than protein content. These data suggest that with higher muscle aerobic capacity (CS activity) there is a greater capacity for carbohydrate oxidation (E1␣), in concert with higher potential for PDH activation (PDP activity). carbohydrate oxidation; PDH; PDP1; E1␣; E2; PDK2 PYRUVATE DEHYDROGENASE (PDH) is a multienzyme complex consisting of multiple copies of E1 (␣ and ␤), E2 (the core of the PDH complex), and E3 subunits, along with an E3 binding protein (E3BP), which serves to bind E3 to the complex (as reviewed by 1, 39). Each of these subunits (with the exception of E3BP) is involved in the conversion of pyruvate to acetylCoA in a stepwise manner. The complex is regulated largely via covalent modification by the addition of a phosphate group to at least one of its three serine residues located on the E1␣ subunit of the complex (15,31,33,34,37). Phosphorylation and inactivation are accomplished by a group of specific PDH kinases (PDK1-4), while dephosphorylation and activation are accomplished by a pair of PDH phosphatases (PDP1 and -2; Refs. 21, 34, 37). Each of these regulatory enzyme isoforms has different specificities and tissue expressions, with PDK2 and PDP1 being the most abundant isoforms in skeletal muscle (3, 11). Both isoforms...

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