sup 13 C and sup 31 P NMR studies of myocardial metabolism

Thesis/Dissertation · Fri Jan 01 04:00:00 EST 1988

OSTI ID:5735607

Laughlin, M R

The fluxes through two enzyme systems have been measured in perfused or in in vivo heart using NMR: phosphocreatine kinase, and glycogen synthase and phosphorylase. The rates of synthesis and degradation of glycogen were monitored in vivo in fed, fasted, and diabetic rat heart during infusions of {sup 13}C-1-glucose and insulin using proton-decoupled {sup 13}C-NMR at 1.9 and 4.7 tesla. The enzyme activities of glycogen synthase and glycogen phosphorylase were also measured in this tissue which had been freeze clamped at the end of the experiment, for comparison with the synthetic rates. For normal fed, fasted, and diabetic animals, synthesis rates were 0.28, 0.16, and 0.15 {mu}mol/min.gww respectively. Glycogen synthase i activity was 0.23, 0.14, and 0.14 {mu}mol/min.gww in these hearts at the end of the experiment, when measured at appropriate substrate and activator concentrations, and follow activation time courses that are consistent with being the main rate determinant for net synthesis in all cases. Turnover of glycogen was studied by observing the preformed {sup 13}C-1-glycogen signal during infusion of {sup 12}C-glucose and insulin, and was found to be close to zero. Extracted phosphorylase a activity was approximately ten times that of synthase i under these circumstances. In order to fully interpret the turnover studies, glycogenolysis of preformed {sup 13}C-glycogen was observed after a bolus of glucagon. The glycogen had either been synthesized from {sup 13}C-1-glucose for a single hour, or during an hour of {sup 13}C-glucose and a subsequent hour of {sup 12}C-glucose infusion. The author observed that breakdown follows an exponential time course related to the phosphorylase a activation state and that the last synthesized glycogen breaks down at the rate of 2.5 {mu}mol/min.gww, five times faster than that synthesized an hour earlier.

• Research Organization: Yale Univ., New Haven, CT (USA)
• OSTI ID: 5735607
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BODY
CARBOHYDRATES
CARBON 13
CARBON ISOTOPES
CARDIOVASCULAR SYSTEM
DIABETES MELLITUS
DISEASES
ENDOCRINE DISEASES
ENZYME ACTIVITY
ENZYMES
EVEN-ODD NUCLEI
FASTING
GLYCOGEN
HEART
IN VIVO
ISOTOPES
LIGHT NUCLEI
MAGNETIC RESONANCE
MAMMALS
METABOLIC DISEASES
METABOLISM
MUSCLES
MYOCARDIUM
NUCLEAR MAGNETIC RESONANCE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PERFUSED ORGANS
PHOSPHORUS 31
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
POLYSACCHARIDES
RATS
RESONANCE
RODENTS
SACCHARIDES
STABLE ISOTOPES
TRANSFERASES
VERTEBRATES