Arginine Synthesis in Healthy Adult Humans

Arginine Synthesis in Healthy Adult Humans: Does Proline or Glutamate Provide the 5-Carbon Chain?

Sponsors

Lead Sponsor: The Hospital for Sick Children

Source 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.

Overall Status Completed
Start Date 2007-09-01
Completion Date 2008-06-01
Primary Completion Date 2008-06-01
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Blood Isotope Levels 8 hours
Enrollment 6
Condition
Intervention

Intervention Type: Other

Intervention Name: 2-15N glutamine

Description: Glutamine with N15 isotope tracer

Arm Group Label: Test Study 1: 2-15N glutamine

Intervention Type: Other

Intervention Name: 15N2 arginine and 15N proline

Description: Arginine and Proline isotope tracers

Arm Group Label: Test Study 2: 15N2 arginine &15N proline

Intervention Type: Other

Intervention Name: 1-13C glutamine

Description: Glutamine carbon isotope tracer

Arm Group Label: Study Test 3: 1-13C glutamine

Eligibility

Criteria:

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

Gender:

Male

Minimum Age:

18 Years

Maximum Age:

55 Years

Healthy Volunteers:

Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Paul Pencharz, MD Principal Investigator The Hospital for Sick Children
Location
Facility: The Hospital for Sick Children
Location Countries

Canada

Verification Date

2018-01-01

Responsible Party

Type: Principal Investigator

Investigator Affiliation: The Hospital for Sick Children

Investigator Full Name: Dr. Paul Pencharz

Investigator Title: Emeritus Scientist

Keywords
Has Expanded Access No
Number Of Arms 3
Arm Group

Label: Test Study 1: 2-15N glutamine

Type: Active Comparator

Description: To determine the contributions make by glutamine to the provision of nitrogen for ornithine, citrulline and arginine syntesis in adults.

Label: Test Study 2: 15N2 arginine &15N proline

Type: Active Comparator

Description: administration of 15N2 arginine &15N proline to measure arginine and proline flux

Label: Study Test 3: 1-13C glutamine

Type: Active Comparator

Description: to determine to contribution of glutamine to the carbon skeleton of ornithine, citrulline and arginine in adults.

Study Design Info

Allocation: Randomized

Intervention Model: Single Group Assignment

Primary Purpose: Diagnostic

Masking: None (Open Label)

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