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
| Autor: | Randall A. Hawkins, Jorge R. Barrio, Sung-Cheng Huang, Michael E. Phelps, Randy E. Keen |
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| Rok vydání: | 1989 |
| Předmět: |
Intracellular Fluid
Male RNA Transfer Leu Biological Transport Active Nerve Tissue Proteins Biology Transaminase chemistry.chemical_compound Biosynthesis Leucine In vivo Protein biosynthesis Animals Carbon Radioisotopes Amino Acids Protein Precursors Catabolism Brain Rats Inbred Strains RNA Transfer Amino Acid-Specific Keto Acids Rats Kinetics Neurology chemistry Biochemistry Specific activity Neurology (clinical) Extracellular Space Cardiology and Cardiovascular Medicine Intracellular Tomography Emission-Computed |
| Zdroj: | Journal of Cerebral Blood Flow & Metabolism. 9:429-445 |
| ISSN: | 1559-7016 0271-678X |
| DOI: | 10.1038/jcbfm.1989.67 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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