Arginine Synthesis in Healthy Adult Humans: Does Proline or Glutamate Provide the 5-Carbon Chain?
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Blood Isotope Levels
Study Overview
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:
- determine the flux of arginine and proline in healthy adult volunteers
- determine and compare the flux of carbon and nitrogen labeled glutamine
- demonstrate whether glutamine or proline provides the carbon backbone for ornithine, citrulline and arginine in adults.
- the source of the N atoms in ornithine, citrulline and arginine.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
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
Arms & Interventions
Test Study 1: 2-15N glutamine
To determine the contributions make by glutamine to the provision of nitrogen for ornithine, citrulline and arginine syntesis in adults.
Intervention: 2-15N glutamine (Other)
Test Study 2: 15N2 arginine &15N proline
administration of 15N2 arginine &15N proline to measure arginine and proline flux
Intervention: 15N2 arginine and 15N proline (Other)
Study Test 3: 1-13C glutamine
to determine to contribution of glutamine to the carbon skeleton of ornithine, citrulline and arginine in adults.
Intervention: 1-13C glutamine (Other)
Outcomes
Primary Outcomes
Blood Isotope Levels
Time Frame: 8 hours
Secondary Outcomes
No secondary outcomes reported
Investigators
Dr. Paul Pencharz
Emeritus Scientist
The Hospital for Sick Children