The measurement of regional rates of cerebral protein synthesis in vivo

1991 ◽  
Vol 16 (9) ◽  
pp. 1037-1046 ◽  
Author(s):  
Carolyn Beebe Smith
Keyword(s):  
Protein Synthesis ◽  
Cerebral Protein Synthesis

scholarly journals In vivo Cerebral Protein Synthesis Rates with Leucyl-Transfer RNA Used as a Precursor Pool: Determination of Biochemical Parameters to Structure Tracer Kinetic Models for Positron Emission Tomography

1989 ◽  
Vol 9 (4) ◽  
pp. 429-445 ◽  
Author(s):  
Randy E. Keen ◽  
Jorge R. Barrio ◽  
Sung-Cheng Huang ◽  
Randall A. Hawkins ◽  
Michael E. Phelps
Keyword(s):  
Positron Emission Tomography ◽  
Protein Synthesis ◽  
Bolus Injection ◽  
Emission Tomography ◽  
Precursor Pool ◽  
Leucine Oxidation ◽  
Positron Emission ◽  
Tissue Compartments ◽  
Cerebral Protein Synthesis

Leucine oxidation and incorporation into proteins were examined in the in vivo rat brain to determine rates and compartmentation of these processes for the purpose of structuring mathematical compartmental models for the noninvasive estimation of in vivo human cerebral protein synthesis rates (CPSR) using positron emission tomography (PET). Leucine specific activity (SA) in arterial plasma and intracellular free amino acids, leucyl-tRNA, α-ketoisocaproic acid (KIC), and protein were determined in whole brain of the adult rat during the first 35 min after intravenous bolus injection of l-[1-14C]leucine. Incorporation of leucine into proteins accounted for 90% of total brain radioactivity at 35 min. The lack of [14C]KIC buildup indicates that leucine oxidation in brain is transaminase limited. Characteristic specific activities were maximal between 0 to 2 min after bolus injection with subsequent decline following the pattern: plasma leucine ≥ leucyl-tRNA ≈ KIC > intracellular leucine. The time integral of leucine SA in plasma was about four times that of tissue leucine and twice those of leucyl-tRNA and KIC, indicating the existence of free leucine, leucyl-tRNA, and KIC tissue compartments, communicating directly with plasma, and separate secondary free leucine, leucyl-tRNA, and KIC tissue compartments originating in unlabeled leucine from proteolysis. Therefore, a relatively simple model configuration based on the key assumptions that (a) protein incorporation and catabolism proceed from a precursor pool communicating with the plasma space, and (b) leucine catabolism is transaminase limited is justified for the in vivo assessment of CPSR from exogenous leucine sources using PET in humans.

scholarly journals Measurement of Regional Rates of Cerebral Protein Synthesis with L-[1-11C]leucine and PET with Correction for Recycling of Tissue Amino Acids: II. Validation in Rhesus Monkeys

2005 ◽  
Vol 25 (5) ◽  
pp. 629-640 ◽  
Author(s):  
Carolyn Beebe Smith ◽  
Kathleen C Schmidt ◽  
Mei Qin ◽  
Thomas V Burlin ◽  
Michelle P Cook ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Excellent Agreement ◽  
Kinetic Modeling ◽  
Precursor Pool ◽  
Modeling Approach ◽  
Positron Emission ◽  
Arterial Plasma ◽  
Cerebral Protein Synthesis

The confounding effect of recycling of amino acids derived from tissue protein breakdown into the precursor pool for protein synthesis has been an obstacle to adapting in vivo methods for determination of regional rates of cerebral protein synthesis (rCPS) to positron emission tomography (PET). We used a kinetic modeling approach to estimate λ, the fraction of the precursor pool for protein synthesis derived from arterial plasma, and to measure rCPS in three anesthetized adult monkeys dynamically scanned after a bolus injection of L-[1-11C]leucine. In the same animals, λ was directly measured in a steady-state terminal experiment, and values showed excellent agreement with those estimated in the PET studies. In three additional monkeys rCPS was determined with the quantitative autoradiographic L-[1-14C]leucine method. In whole brain and cerebellum, rates of protein synthesis determined with the autoradiographic method were in excellent agreement with those determined with PET, and regional values were in good agreement when differences in spatial resolution of the two methods were taken into account. Low intrasubject variability was found on repeated PET studies. Our results in anesthetized monkey indicate that, by using a kinetic modeling approach to correct for recycling of tissue amino acids, quantitatively accurate and reproducible measurement of rCPS is possible with L-[1-11C]leucine and PET.

Quantitative Autoradiographic Method for Determination of Regional Rates of Cerebral Protein Synthesis In Vivo

10.3791/58503 ◽  
2019 ◽  
Author(s):  
R. Michelle Saré ◽  
Anita Torossian ◽  
Michael Rosenheck ◽  
Tianjian Huang ◽  
Carolyn Beebe Smith
Keyword(s):  
Protein Synthesis ◽  
Autoradiographic Method ◽  
Cerebral Protein Synthesis

Respiratory energy requirements and rate of protein turnover in vivo determined by the use of an inhibitor of protein synthesis and a probe to assess its effect

1994 ◽  
Vol 92 (4) ◽  
pp. 585-594 ◽  
Author(s):  
T. J. Bouma ◽  
R. De Visser ◽  
J. H. J. A. Janssen ◽  
M. J. De Kock ◽  
P H. Van Leeuwen ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Turnover ◽  
Energy Requirements ◽  
Inhibitor Of Protein Synthesis
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