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Metabolic Fate of β-Aspartyl-(14)C-glycine in Normal Young Rats
H Tanaka1, K Noutomi1, M Akiba1
1a Department of Agricultural Chemistry, Faculty of Agriculture , Utsunomiya University, Mine-350 Utsunomiya , Tochigi 321 , Japan.
Bioscience, Biotechnology, and Biochemistry
|June 10, 2016
Summary
In rats, the dipeptide beta-aspartylglycine is rapidly excreted in urine with minimal hydrolysis, unlike alpha-aspartylglycine which is readily broken down.
Area of Science:
- Biochemistry
- Metabolism
- Renal Physiology
Background:
- Understanding the metabolic fate of dipeptides is crucial for comprehending amino acid metabolism and excretion pathways.
- The differential metabolic processing of peptide isomers can significantly impact their physiological roles and toxicological profiles.
Purpose of the Study:
- To investigate and compare the in vivo and in vitro metabolic fate of alpha-aspartylglycine and beta-aspartylglycine in rats.
- To determine the hydrolysis rates and excretion patterns of these isomeric dipeptides in normal young rats.
Main Methods:
- Synthesis of radiolabeled alpha- and beta-L-aspartyl-[U-(14)C]glycine.
- Administration of labeled dipeptides to normal young rats via intraperitoneal injection.
- Analysis of radioactivity in urine, expired carbon dioxide, and tissue slices (kidney, liver, small intestine) over a 24-hour period.
- In vitro hydrolysis studies using tissue slices to assess enzymatic breakdown.
Main Results:
- Beta-aspartylglycine was predominantly excreted unchanged in urine (approx. 66% of dose), with minimal recovery in expired CO2 (8%).
- Alpha-aspartylglycine showed significantly lower urinary excretion (3%) but higher recovery in expired CO2 (22%), indicating greater catabolism.
- In vitro studies revealed rapid and near-complete hydrolysis of alpha-aspartylglycine in kidney, liver, and small intestine, releasing free glycine.
- Beta-aspartylglycine was poorly hydrolyzed in liver and small intestine, and only slightly in kidney, suggesting resistance to enzymatic breakdown.
Conclusions:
- In normal young rats, beta-aspartylglycine is largely resistant to hydrolysis and is rapidly excreted unchanged in the urine.
- Alpha-aspartylglycine, conversely, undergoes significant hydrolysis, releasing its constituent amino acids for further metabolism.
- These findings highlight the distinct metabolic pathways and physiological handling of alpha- and beta-aspartylglycine isomers in rats.

