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

Journal Article · Tue Aug 01 04:00:00 EDT 1989 · J. Cereb. Blood Flow Metab.; (United States)

DOI:https://doi.org/10.1038/jcbfm.1989.67· OSTI ID:5700087

Keen, R E; Barrio, J R; Huang, S C; Hawkins, R A; Phelps, M E

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), Journal Name: J. Cereb. Blood Flow Metab.; (United States) Vol. 9:4; ISSN JCBMD
• Country of Publication: United States
• Language: English

Related Subjects

550501 -- Metabolism-- Tracer Techniques
550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINO ACIDS
ANIMALS
BIOLOGICAL FUNCTIONS
BLOOD FLOW
BODY
BRAIN
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CATABOLISM
CENTRAL NERVOUS SYSTEM
COMPUTERIZED TOMOGRAPHY
DIAGNOSTIC TECHNIQUES
EMISSION COMPUTED TOMOGRAPHY
EXTRACELLULAR SPACE
FUNCTIONS
IN VIVO
ISOTOPE APPLICATIONS
KETO ACIDS
LABELLED COMPOUNDS
LEUCINE
MAMMALS
MAN
MATHEMATICAL MODELS
MEMBRANE TRANSPORT
METABOLISM
NERVOUS SYSTEM
NUCLEIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
POSITRON COMPUTED TOMOGRAPHY
PRECURSOR
PRIMATES
RATS
RNA
RODENTS
SPACE
TOMOGRAPHY
TRACER TECHNIQUES
TRANSFER RNA
VERTEBRATES