In Vivo Utilization of Cystine-Containing Synthetic Short-Chain Peptides after Intravenous Bolus Injection in the Rat

Abstract

For the first time, in vivo utilization of two highly soluble and stable cystine-containing synthetic short-chain peptides, bis-L-alanyl-L-cystine and bis-glycyl-L-cystine, were investigated in adult rats. Within 5 min after an intravenous bolus, blood samples were drawn (inferior vena cava) and plasma amino acid and peptide levels were determined using RP-HPLC (precolumn derivatization with 5-dimethylaminonaphthalene-1-sulfonylchloride). Both peptides were rapidly cleared from plasma (estimated elimination t1/2: 4 min for the glycyl peptide and less than 2 min for the alanyl peptide). The initial high amounts of mono-L-alanyl-L-cystine and mono-glycyl-L-cystine as well as the prompt increase of the constituent free amino acids alanine, glycine and cystine strongly suggest that the peptide disappearance is mainly due to a very fast two-step hydrolysis in the extracellular compartment, presumably catalyzed by soluble and/or plasma membrane-bound peptidases. The observed rapid hydrolysis may serve as first evidence that short-chain peptides with C-terminal cystine residue may represent efficient sources of free cystine in parenteral nutrition.

Kinetics of plasma lysine after oral and parenteral administration to pigs.

“…The rate of absorption corresponded well to portal absorption data obtained by Rerat (1985). Also, peptide degradation products from enzymatic hydrolysis of proteins in the digestive tract may be absorbed readily (Kushak & Basova, 1988) and are then rapidly degraded after appearance in systemic circulation (Stehle et al, 1988). The second postprandi al maximum of plasma amino acids, as this was observed frequently, may be related to the digestion and reabsorption of amino acids, that were incorporated in digestion-related secretory proteins or cellular proteins from the gastro-intestinal mucosa.…”

The Significance of Peptides in Clinical Nutrition

“…N,N-bis-L-alanyl-L,L-cystine and N,N-bis-L-glycyl-L,L-cystine are rapidly uti lized after bolus injection in the rat (162,187). taking into account the activity of membrane peptidases of liver and muscle.…”

New Nitrogen-Containing Substrates in Artificial Nutrition

“…Pharmacokinetic evaluation after intravenous supply of acetylcysteine in humans exhibited an elimination half-life of 2.3 h, a value which is indeed ca. 4o-fold higher than those observed for cystine-containing peptides [89].…”