Cerebral protein synthesis rates in vivo: Estimation via biochemical analyses and tracer kinetic modeling

Conference · Wed May 01 04:00:00 EDT 1985 · J. Nucl. Med.; (United States)

OSTI ID:7034870

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

In this work the authors investigated several biochemical parameters affecting the application of kinetic modeling to the determination of cerebral protein biosynthesis rates. Adult male rats fed ad libitum were injected intravenously with L-(1-/sup 14/C)leucine (30 ..mu.. Ci bolus; 50 mCi/mmol) and the temporal sequence of leucine specific activities (SA) in plasma and tissue, as well as for the reaction product (proteins) in brain tissue were determined over 35 minutes. After rapid increase following bolus injection of L-(1-/sup 14/C)leucine, the temporal sequence of brain free leucine SA decreased. The time course of plasma free leucine SA was significantly higher (>2 times), but essentially paralleled the tissue free leucine SA. Analyses of brain extracts demonstrated that at 5 min almost 50% of the brain activity was in proteins, with most of the remaining /sup 14/C in the free leucine pool. At 35 min, 91% of the brain activity was in proteins. A small fraction of the activity (4%) was not identified. Calculation of the amino acid precursor pool SA revealed that it was close to that of plasma. This means that plasma amino acids may be the main contributors to the amino acid pool for transfer RNA amino acylation. Incorporation of these data into a compartmental tracer kinetic model allowed for the calculation of protein biosynthesis rates for whole rat brain (3.0 mole leucine/min/g tissue), consistent with previous findings. Studies in 10 normal human subjects with PET using this model and L-(1-/sup 11/C)leucine have yielded good fits and reproducible estimates of the model rate constants (k/sub 1/ = 0.049 +- 0.011; k/sub 2/ = 0.253 +- 0.059; k/sub 3/ = 0.138 +- 0.032; k/sub 4/ = 0.048 +- 0.002; k/sub 5/ = 0.098 +- 0.016); protein biosynthesis rates (0.82 +- 0.11 nm/min/g) and leucine metabolic rates (1.2 +- 0.2 nm/min/g) in cortex.

• Research Organization: UCLA School of Medicine, Los Angeles, CA 90024
• OSTI ID: 7034870
• Report Number(s): CONF-850611-
• Conference Information: Journal Name: J. Nucl. Med.; (United States) Journal Volume: 26:5
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
550501 -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOCHEMISTRY
BIOSYNTHESIS
BLOOD CHEMISTRY
BODY
BRAIN
CARBON 11
CARBON 14 COMPOUNDS
CARBON ISOTOPES
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CHEMISTRY
COMPUTERIZED TOMOGRAPHY
DIAGNOSTIC TECHNIQUES
DISTRIBUTION
EMISSION COMPUTED TOMOGRAPHY
EVEN-ODD NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LABELLED POOL TECHNIQUES
LEUCINE
LIGHT NUCLEI
MAMMALS
MAN
MATHEMATICAL MODELS
METABOLISM
MINUTES LIVING RADIOISOTOPES
NERVOUS SYSTEM
NUCLEI
NUCLEIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
POSITRON COMPUTED TOMOGRAPHY
PRIMATES
PROTEINS
RADIOISOTOPES
RADIONUCLIDE KINETICS
RATS
REACTION KINETICS
RNA
RODENTS
SYNTHESIS
TISSUE DISTRIBUTION
TOMOGRAPHY
TRACER TECHNIQUES
TRANSFER RNA
VERTEBRATES