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Intravenous gamma-glutamyl-tyrosine elevates brain tyrosine but not catecholamine concentrations in normal rats
D C Berger1, M A Hilton, F K Hilton
1Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, KY 40292, USA.
Insights
Intravenous gamma-glutamyl-tyrosine (Glu(Tyr)) supplementation effectively increases tyrosine (Tyr) levels in plasma and brain tissue. This peptide offers a soluble alternative for Tyr delivery in clinical settings like total parenteral nutrition (TPN).
Area of Science:
- Biochemistry
- Neuroscience
- Clinical Nutrition
Background:
- Tyrosine (Tyr) supplementation is clinically relevant but limited by poor solubility for intravenous administration.
- Total parenteral nutrition (TPN) often results in reduced plasma and brain Tyr levels, impacting physiological functions.
- Previous studies indicated gamma-glutamyl-Tyr [Glu(Tyr)] peptide normalizes plasma Tyr and increases brain Tyr in rats.
Purpose of the Study:
- To evaluate the in vivo behavior and efficacy of intravenous gamma-glutamyl-Tyr [Glu(Tyr)] for tyrosine (Tyr) supplementation.
- To determine plasma and brain Tyr concentrations following Glu(Tyr) infusion in a rat model.
- To assess the impact of Glu(Tyr) infusion on neurotransmitter precursor levels and excretion.
Main Methods:
- Intravenous infusion of 20 mmol/L Glu(Tyr) into rats over 8 hours, with increasing infusion rates.
- Measurement of plasma Tyr and Glu(Tyr) concentrations at peak infusion rates.
- Analysis of brain Tyr concentrations and neurotransmitter levels (norepinephrine, dopamine, homovanillic acid) in specific brain regions.
Main Results:
- Plasma Tyr and Glu(Tyr) reached plateau concentrations of 326 and 252 µmol/L, respectively.
- Brain Tyr concentrations significantly increased in rats infused with Glu(Tyr) (264 nmol/g) compared to controls (71 nmol/g).
- No significant differences in norepinephrine, dopamine, or homovanillic acid levels were observed; intact Glu(Tyr) was not detected in the brain, and minimal amounts were found in urine.
Conclusions:
- Intravenous gamma-glutamyl-Tyr [Glu(Tyr)] is an effective method for increasing tyrosine (Tyr) availability in both plasma and brain tissue.
- Glu(Tyr) appears to be a safe and soluble source of Tyr for potential use in TPN and other clinical applications.
- Further research is warranted to explore the long-term effects and broader clinical utility of Glu(Tyr) supplementation.
Abstract:
A number of clinical situations may benefit from intravenous supplements of tyrosine (Tyr). In total parenteral nutrition (TPN), the supply of Tyr is limited by its poor solubility. In both rats and infants maintained on pediatric TPN, plasma Tyr levels are approximately 30% of normal, and in rat brains Tyr concentrations are similarly reduced. We reported previously that supplementing a TPN solution with the soluble peptide, gamma-glutamyl-Tyr [Glu(Tyr)], normalizes plasma Tyr and doubles brain Tyr in rats. To assess more fully the behavior of intravenous Glu(Tyr) in vivo, 20 mmol/L Glu(Tyr) was infused into the inferior vena cava of rats at rates increased every 2 hours over an 8-hour period (300 to 450 mumol Glu(Tyr)/kg body weight/h). The surgical procedure for catheterization is described. At the maximum rate of infusion, plasma Tyr and Glu(Tyr) concentrations reached mean plateau values of 326 and 252 mumol/L, respectively. Brain Tyr concentrations were 71 and 264 nmol/g wet weight in control rats infused with heparinized saline (SAL group) and rats infused with Glu(Tyr) (PEP group) respectively. No differences were found in concentrations of norepinephrine (NE), dopamine (DA), or homovanillic acid (HVA) in prefrontal cortex (PFC), striatum (STR), or remaining brain (RB) tissue in PEP and SAL rats. We did not detect undergraded Glu(Tyr) in the brain, and less than 0.5% of infused Glu(Tyr) appeared in the urine.