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An analysis of metabolic fluxes in c...

Crowther, Gregory John.

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An analysis of metabolic fluxes in contracting human skeletal muscle.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	An analysis of metabolic fluxes in contracting human skeletal muscle./
Author:	Crowther, Gregory John.
Description:	135 p.
Notes:	Chairpersons: Kevin E. Conley; Martin J. Kushmerick.
Contained By:	Dissertation Abstracts International63-05B.
Subject:	Biology, Animal Physiology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3053491
ISBN:	0493681655

An analysis of metabolic fluxes in contracting human skeletal muscle.
Crowther, Gregory John.

An analysis of metabolic fluxes in contracting human skeletal muscle. - 135 p.

Chairpersons: Kevin E. Conley; Martin J. Kushmerick.

Thesis (Ph.D.)--University of Washington, 2002.

Although muscle metabolism has been a subject of scientific scrutiny for the last 70+ years, many important questions in this area remain unresolved. They include: how does voluntary exercise affect the quantification of whole-muscle data? What factors are responsible for the large changes in glycolytic flux seen during rest-to-exercise and exercise-to-rest transitions? How do the metabolic capacities of diabetic and athletic individuals differ from those of normal individuals? In the present work, these questions were addressed using phosphorus-31 magnetic resonance Spectroscopy (<super>31</super>P MRS). Subjects exercised their ankle dorsiflexor muscles by performing voluntary isometric contractions against the resistance of a plastic footholder. In some experiments, a blood pressure cuff was used to occlude blood flow to the active muscle. Magnetic resonance spectra of the dorsiflexors were acquired before, during, and after exercise. The contractile cost of exercise was considered to be the rate of phosphocreatine (PCr) decline at the start of exercise; the glycolytic flux was calculated from changes in pH, PCr, inorganic phosphate (Pi), and phosphomonoesters; and the oxidative recovery rate constant <italic> k</italic>PCr was calculated from PCr recovery kinetics following exercise. The present studies yielded several novel findings: (1) differences in muscle fiber recruitment can affect the measurement of <italic>k</italic> PCr (and thus estimates of oxidative capacity); (2) Pi, ADP, and/or AMP must be elevated above basal levels in order for glycolytic flux to begin; (3) the inactivation of glycolysis after exercise reflects the cessation of contractile activity and is mediated within the glycolytic pathway rather than via the control of glycogen breakdown; (4) relative to the muscles of control subjects, the muscles of subjects with well-managed type 1 diabetes mellitus are shifted in the direction of fast-twitch glycolytic metabolism; (5) the differences in the muscle metabolism of sprinters and distance runners are small relative to the 2- to 3-fold variation seen in the metabolic capacities of individual human muscle fibers. Thus <super> 31</super>P MRS is a valuable tool both for probing the fundamental mechanisms of flux control in vivo and for profiling the metabolic traits of different individuals and groups.

ISBN: 0493681655Subjects--Topical Terms:

1017835
Biology, Animal Physiology.

An analysis of metabolic fluxes in contracting human skeletal muscle.
LDR:03382nam 2200289 a 45 001 929381
005 20110427
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020 $a 0493681655
035 $a (UnM)AAI3053491
035 $a AAI3053491
040 $a UnM $c UnM
100 1 $a Crowther, Gregory John. $3 1252866
245 1 0 $a An analysis of metabolic fluxes in contracting human skeletal muscle.
300 $a 135 p.
500 $a Chairpersons: Kevin E. Conley; Martin J. Kushmerick.
500 $a Source: Dissertation Abstracts International, Volume: 63-05, Section: B, page: 2139.
502 $a Thesis (Ph.D.)--University of Washington, 2002.
520 $a Although muscle metabolism has been a subject of scientific scrutiny for the last 70+ years, many important questions in this area remain unresolved. They include: how does voluntary exercise affect the quantification of whole-muscle data? What factors are responsible for the large changes in glycolytic flux seen during rest-to-exercise and exercise-to-rest transitions? How do the metabolic capacities of diabetic and athletic individuals differ from those of normal individuals? In the present work, these questions were addressed using phosphorus-31 magnetic resonance Spectroscopy (<super>31</super>P MRS). Subjects exercised their ankle dorsiflexor muscles by performing voluntary isometric contractions against the resistance of a plastic footholder. In some experiments, a blood pressure cuff was used to occlude blood flow to the active muscle. Magnetic resonance spectra of the dorsiflexors were acquired before, during, and after exercise. The contractile cost of exercise was considered to be the rate of phosphocreatine (PCr) decline at the start of exercise; the glycolytic flux was calculated from changes in pH, PCr, inorganic phosphate (Pi), and phosphomonoesters; and the oxidative recovery rate constant <italic> k</italic>PCr was calculated from PCr recovery kinetics following exercise. The present studies yielded several novel findings: (1) differences in muscle fiber recruitment can affect the measurement of <italic>k</italic> PCr (and thus estimates of oxidative capacity); (2) Pi, ADP, and/or AMP must be elevated above basal levels in order for glycolytic flux to begin; (3) the inactivation of glycolysis after exercise reflects the cessation of contractile activity and is mediated within the glycolytic pathway rather than via the control of glycogen breakdown; (4) relative to the muscles of control subjects, the muscles of subjects with well-managed type 1 diabetes mellitus are shifted in the direction of fast-twitch glycolytic metabolism; (5) the differences in the muscle metabolism of sprinters and distance runners are small relative to the 2- to 3-fold variation seen in the metabolic capacities of individual human muscle fibers. Thus <super> 31</super>P MRS is a valuable tool both for probing the fundamental mechanisms of flux control in vivo and for profiling the metabolic traits of different individuals and groups.
590 $a School code: 0250.
650 4 $a Biology, Animal Physiology. $3 1017835
650 4 $a Health Sciences, Recreation. $3 1018003
690 $a 0433
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710 2 0 $a University of Washington. $3 545923
773 0 $t Dissertation Abstracts International $g 63-05B.
790 $a 0250
790 1 0 $a Conley, Kevin E., $e advisor
790 1 0 $a Kushmerick, Martin J., $e advisor
791 $a Ph.D.
792 $a 2002
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3053491