Arginine Synthesis in Healthy Adult Humans

Not Applicable

Completed

• Conditions: Healthy
• Interventions: Other: 1-13C glutamine; Other: 15N2 arginine and 15N proline; Other: 2-15N glutamine

• Registration Number: NCT01912235
• Lead Sponsor: The Hospital for Sick Children

Brief Summary

Arginine synthesis in mammals is a complex process involving at least 8 enzymes and intracellular and interorgan transfer of substrates.

The investigators have shown in our neonatal studies that there is no conversion of glutamate to arginine but proline label appears in ornithine, citrulline and arginine. It is clear therefore that arginine is synthesized in human neonates from proline.

In adults the source of the carbon backbone is less clear.

Detailed Description

Through a series of test in healthy adults using tandem mass spectrometry with carbon labeled GLN and nitrogen labeled PRO to determine the dietary source for the carbon chain of ORN, CIT and ARG. Additionally, using Nitrogen labeled GLN, we will identify the source of the nitrogen atoms in these amino acids.

Using guanidino - 15N2 arginine, 1-13C Glutamine, 2-15N Glutamine and 15N Proline we will be able to:

1. determine the flux of arginine and proline in healthy adult volunteers

2. determine and compare the flux of carbon and nitrogen labeled glutamine

3. demonstrate whether glutamine or proline provides the carbon backbone for ornithine, citrulline and arginine in adults.

4. the source of the N atoms in ornithine, citrulline and arginine.

Study Timeline

• Study Start: 2007-09
• Primary Completion: 2008-06
• Study Completion: 2008-06
• Study First Submitted: 2013-07-26
• Study First Submitted QC: 2013-07-30
• Study First Posted: 2013-07-31
• Status Verified: 2018-01
• Last Update Submitted: 2018-01-05
• Last Update Posted: 2018-01-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 6

Inclusion Criteria

• 5 men of average weight 80 kg will be studied
• healthy, with no know disease of liver, and/or kidney
• weight stable

Exclusion Criteria

• weith loss or gain over the last three months
• on medications known to affect amino acid metabolism
• known liver, kidney disease condition

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Study Test 3: 1-13C glutamine	1-13C glutamine	to determine to contribution of glutamine to the carbon skeleton of ornithine, citrulline and arginine in adults.
Test Study 2: 15N2 arginine &15N proline	15N2 arginine and 15N proline	administration of 15N2 arginine \&15N proline to measure arginine and proline flux
Test Study 1: 2-15N glutamine	2-15N glutamine	To determine the contributions make by glutamine to the provision of nitrogen for ornithine, citrulline and arginine syntesis in adults.

Primary Outcome Measures

Name	Time	Method
Blood Isotope Levels	8 hours

Trial Locations

Locations (1)

The Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada