Arginine Synthesis in Healthy Adult Humans

The Hospital for Sick Children

Status: Completed

Conditions: Healthy

Treatments: Other: 15N2 arginine and 15N proline; Other: 2-15N glutamine; Other: 1-13C glutamine

Study type: Interventional

Funder types: Other

Identifiers

NCT01912235

02/02/2010

Details and patient eligibility

About

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.

Full 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.

Enrollment: 6 patients

Sex: Male

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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6 participants in 3 patient groups

Test Study 1: 2-15N glutamine

Active Comparator group

Description:

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

Treatment:

Other: 2-15N glutamine

Test Study 2: 15N2 arginine &15N proline

Active Comparator group

Description:

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

Treatment:

Other: 15N2 arginine and 15N proline

Study Test 3: 1-13C glutamine

Active Comparator group

Description:

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

Treatment:

Other: 1-13C glutamine