Role of Mitochondrial Lactate Dehydrogenase and Lactate Oxidation in the Intracellular Lactate Shuttle

( George A. Brooks ),( Herve Dubouchaud ),( Marcia Brown ),( James P. Sicurello ),( C. Eric Butz ) 한국스포츠정책과학원(구 한국스포츠개발원) 1999 International Journal of Applied Sports Sciences Vol.11 No.1

To evaluate the potential role of mitochondrial lactate dehydrogenase (LDH) in tissue lactate clearance and oxidation in vivo, isolated rat liver, cardiac, and skeletal muscle mitochondria were incubated with lactate, pyruvate, glutamate, and succinate. As well, a-cyano-4-hydroxycin-namate (CINN), a known monocarboxylate transport inhibitor, and oxamate, a known LDH inhibitor were used. Mitochondria readily oxidized pyruvate and lactate, with similar state 3 and 4 respiratory rates, respiratory control (state 3ystate 4), and ADPyO ratios. With lactate or pyruvate as substrates, a-cyano-4-hydroxycinnamate blocked the respira-tory response to added ADP, but the block was bypassed by addition of glutamate (complex I-linked) and succinate (complex 11 linked) substrates. Oxamate increased pyruvate (`10-40%), but blocked lanctate oxidation. Gel electrophoresis and electron microscopy indicated LDH isoenzyme distribution patterns to display tissue specificity, but the LDH isoenzyme patterns in isolated mitochondria were distinct from those in surrounding cell compartments. In heart, LDH-1 (H4) was concentrated in mitochondria whereas LDH-5 (M4) was present in both mitochondria and surrounding cytosol and organelles. LDH-5 predominated in liver but was more abundant in mitochondria than elsewhere. Because lactate exceeds cytosolic pyruvate concentration by an order of magnitude, we conclude that lactate is the predominant monocarboxylate oxidized by mitochondria in vivo. Mammalian liver and striated muscle mitochondria can oxidize exogenous lactate because of an internal LDH pool that facilitates lactate oxidation.

Tracing the lactate shuttle to the mitochondrial reticulum

Brooks George A.,Curl Casey C.,Leija Robert G.,Osmond Adam D.,Duong Justin J.,Arevalo Jose A. 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Isotope tracer infusion studies employing lactate, glucose, glycerol, and fatty acid isotope tracers were central to the deduction and demonstration of the Lactate Shuttle at the whole-body level. In concert with the ability to perform tissue metabolite concentration measurements, as well as determinations of unidirectional and net metabolite exchanges by means of arterial–venous difference (a-v) and blood flow measurements across tissue beds including skeletal muscle, the heart and the brain, lactate shuttling within organs and tissues was made evident. From an extensive body of work on men and women, resting or exercising, before or after endurance training, at sea level or high altitude, we now know that Organ–Organ, Cell–Cell, and Intracellular Lactate Shuttles operate continuously. By means of lactate shuttling, fuel-energy substrates can be exchanged between producer (driver) cells, such as those in skeletal muscle, and consumer (recipient) cells, such as those in the brain, heart, muscle, liver and kidneys. Within tissues, lactate can be exchanged between white and red fibers within a muscle bed and between astrocytes and neurons in the brain. Within cells, lactate can be exchanged between the cytosol and mitochondria and between the cytosol and peroxisomes. Lactate shuttling between driver and recipient cells depends on concentration gradients created by the mitochondrial respiratory apparatus in recipient cells for oxidative disposal of lactate.

Cytokine responses to moderate-intensity leg cycling exercise in follicular and luteal menstrual cycle phases

Suh, Sang Hoon,Gretchen, A. Casazza,George, A. Brooks 한국운동과학회 2003 운동과학 Vol.12 No.4

서상훈. Gretchen A. Casazza·George A. Brooks. 중강도 자전거 운동시 생리주기에 따른 싸이토카인의 반응, 운동과학, 제12권 제4호, 631-640, 2003. 본 연구는 식후 3시간 휴식을 취한 여성을 대상으로 운동강도와 생리주기가 혈장 TNF-α와 Interleukin-6 농도에 미치는 영향을 조사하였다. 정상적인 생리 주기 (23-24 일)를 가진 건강하고 훈련되지 않은 8명의 여성이 휴식 (180 분)과 운동 (45%와 65%, VO₂peak에서 60 분간 자전거 에르고미터를 이용한 운동) 중에 난포기 (FP, 3-9 일)와 황체기 (LP, 18-24 일)에서 연구하였다. 자전거 에르고미터 운동은 런닝시 나타나는 플라이오메트릭 근수측의 근육손상 가능성을 제한하기 위해서 이용되었다. 실험 하루 전 음식섭취는 조절하였다. 혈장 TNF-α와 Interleukin-6 농도는 일라이자 (EISA, Enzyme-Linked ImmunoSorbent Assay)로 측정하였다. 헐장 TNF-α와 Interleukin군 농도는 운동 중에 약간 증가하였으나, 유의한 차이를 보이지 않았다 (p>.05). 혈장 TNF-α와 Interleukin군 농도는 난포기에 비해 황체기에서 낮게 나타나는 경향을 보였지만, 유의한 차이는 발견되지 않았다 (p>,05).운동강도 (45%와 65% V0₂peak)에 따른 혈장 TNF-α와 Interleukin-6 농도 변화는 유의한 차이를 보이지 않았다 (p>.05). 따라서 본 연구의 결과는 첫째, 중강도 자전거 운동은 젊고 건강한 여성의 염증 반응 사이토카인 (cytokine) 변화를 유발할 가능성이 희박하고, 둘째, 여성 난소 스테로이드 호르몬은 휴식과 운동 중에 철장 사이토카인 반응을 변화시키지 않은 것으로 사료된다. Seo, S.H., G.A. Casazza., G.A. Brooks. Cytokine responses to moderato-intensity leg cycling exorcise in foliicular and luteal menstrual cycle phases. Exercise Science, 12(4): 631-640, 2003. We examined the effects of exorcise Intensity and menstrual cycle phases on plasma concentrations of tumor necrosis factor (TNF-a) and interleukin-6 (IL-6) during rest and exorcise in rested 3-h postabsorptive women. Eight healthy, untrained women with normal menstrual cycles (24-34 days) were studied under conditions of rest (180 min) and exorcise(60 min, leg ergometer cycling at 45 and 65% peak oxygen consumption) during follicular (FP; cycle days 3-9) and luteal(LP; cycle days 18-24) phases. Leg cycling was used to eliminate the possibility of muscle damage from plyometric muscle contractions as occur in running. Dietary intake was controlled for the 24-h immediately preceding each trial. The plasma concentrations of TNF-a and IL-6 were measured by Enzyme-Linked immunoSorbent Assay (ELISA). There was a slight increasen plasma concentrations of TNF-aand IL-6 during exorcise, as compared to rest, but this difference was not significant (p>.05). The plasma levels of TNF-a and IL-6tended to be lower In LP than in FP, but no significant difference was found (p>.05). There were no significant differences in the plasma concentrations of TNf-a and IL-6 due to exorcise Intensity (i.e., exorcise at 45 and 65% V0₂peak). These results are interpreted to mean that moderate-intensity bicycle exorcise is unlikely to induce a change in inflammatory cytokine levels in young healthy women, and that plasma cytokine response during rest and exorcise does not appear to be altered by overian steroid hormones.

Model for Prioritizing Best Management Practice Implementation: Sediment Load Reduction

Jang, Taeil,Vellidis, George,Hyman, Jeffrey B.,Brooks, Erin,Kurkalova, Lyubov A.,Boll, Jan,Cho, Jaepil Springer-Verlag 2013 Environmental management Vol.51 No.1

<P>Understanding the best way to allocate limited resources is a constant challenge for water quality improvement efforts. The synoptic approach is a tool for geographic prioritization of these efforts. It uses a benefit-cost framework to calculate indices for functional criteria in subunits (watersheds, counties) of a region and then rank the subunits. The synoptic approach was specifically designed to incorporate best professional judgment in cases where information and resources are limited. To date, the synoptic approach has been applied primarily to local or regional wetland restoration prioritization projects. The goal of this work was to develop a synoptic model for prioritizing watersheds within which suites of agricultural best management practices (BMPs) can be implemented to reduce sediment load at the watershed outlets. The model ranks candidate watersheds within an ecoregion or river basin so that BMP implementation within the highest ranked watersheds will result in the most sediment load reduction per conservation dollar invested. The model can be applied anywhere and at many scales provided that the selected suite of BMPs is appropriate for the evaluation area’s biophysical and climatic conditions. The model was specifically developed as a tool for prioritizing BMP implementation efforts in ecoregions containing watersheds associated with the USDA-NRCS conservation effects assessment project (CEAP). This paper presents the testing of the model in the little river experimental watershed (LREW) which is located near Tifton, Georgia, USA and is the CEAP watershed representing the southeastern coastal plain. The application of the model to the LREW demonstrated that the model represents the physical drivers of erosion and sediment loading well. The application also showed that the model is quite responsive to social and economic drivers and is, therefore, best applied at a scale large enough to ensure differences in social and economic drivers across the candidate watersheds. The prioritization model will be used for planning purposes. Its results are visualized as maps which enable resource managers to identify watersheds within which BMP implementation would result in the most water quality improvement per conservation dollar invested.</P>

Active Muscle and Whole Body Lactate Kinetics after Endurance Training in Men

( Bryan C. Bergman ),( Eugene E. Wolfel ),( Gail E. Butterfield ),( Gary D. Lopaschuk ),( Gretchen A. Casazza ),( Michael A. Horning ),( George A. Brooks ) 한국스포츠정책과학원(구 한국스포츠개발원) 1999 International Journal of Applied Sports Sciences Vol.11 No.1

We evaluated the hypotheses that endurance training decreases arterial lactate concentration ([lactate]a) during continuous exer-cise by decreasing net lactate release (L) and appearance rates (Ra) and increasing metabolic clearance rate (MCR). Measurements were made at two intensities before [45 and 65% peak O2 consumption (VO2peak)] and after training [65% pretraining VO2peak, same absolute workload (ABT), and 65% posttraining VO2peak, same relative intensity (RLT)]. Nine men (27.4 2.0 yr) trained for 9 wk on a cycle ergometer, 5 times/wk at 75% VO2peak, Compared with the 65% VO2peak:, pretraining condition (4.75 0.4 mM), [lactate]a decreased at ABT (41%) and RLT (21%) (P,0.05). L decreased at ABT but not at RLT. Leg lactate uptake and oxidation were unchanged at ABT but increased at RLT. MCR was unchanged at ABT but increased at RLT. We conclude that 1) active skeletal muscle is not solely responsible for elevated [lactate]a; and 2) training increases leg lactate clearance, decreases whole body and leg lactate production at a given moderate-intensity power output, and increases both whole body and leg lactate clearance at a high relative power output.

홀로신 중기 이후 해안사구지대의 형성동인

유근배,George A. Brook,류호상,신영호,김성환,Fong Z. Brook 대한지리학회 2009 대한지리학회 학술대회논문집 Vol.- No.-

Episodic Coastal Dune Development in the Taean Peninsula and Anmyeon Island, Korea, During the Mid to Late Holocene

YU Keun Bae,BROOK George A,RHEW Hosahng,SHIN Young Ho,KIM Sung Hwan,BROOK Fong Z 대한지리학회 2008 대한지리학회 컨퍼런스 자료집 Vol.2 No.-