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
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, alpha-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-/sup 14/C)leucine. Incorporation of leucine into proteins accounted for 90% of total brain radioactivity at 35 min. The lack of (/sup 14/C)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 greater than or equal to leucyl-tRNA approximately KIC greater than 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.
- Research Organization:
- UCLA School of Medicine, Los Angeles, CA (USA)
- OSTI ID:
- 5700087
- Journal Information:
- J. Cereb. Blood Flow Metab.; (United States), Vol. 9:4
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
BRAIN
POSITRON COMPUTED TOMOGRAPHY
LEUCINE
CATABOLISM
TRANSFER RNA
BIOLOGICAL FUNCTIONS
AMINO ACIDS
BLOOD FLOW
CARBON 14 COMPOUNDS
EXTRACELLULAR SPACE
IN VIVO
KETO ACIDS
MAN
MATHEMATICAL MODELS
MEMBRANE TRANSPORT
PRECURSOR
RATS
TRACER TECHNIQUES
ANIMALS
BODY
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
COMPUTERIZED TOMOGRAPHY
DIAGNOSTIC TECHNIQUES
EMISSION COMPUTED TOMOGRAPHY
FUNCTIONS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
METABOLISM
NERVOUS SYSTEM
NUCLEIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PRIMATES
RNA
RODENTS
SPACE
TOMOGRAPHY
VERTEBRATES
550601* - Medicine- Unsealed Radionuclides in Diagnostics
550501 - Metabolism- Tracer Techniques