Noninvasive evaluation of liver metabolism by 2H and 13C NMR isotopomer analysis of human urine.
Mammalian liver disposes of acetaminophen and other ingested xenobiotics by forming soluble glucuronides that are subsequently removed via renal filtration. When given in combination with the stable isotopes 2H and 13C, the glucuronide of acetaminophen isolated from urine provides a convenient "chemical biopsy" for evaluating intermediary metabolism in the liver. Here, we describe isolation and purification of urinary acetaminophen glucuronide and its conversion to monoacetone glucose (MAG). Subsequent 2H and 13C NMR analysis of MAG from normal volunteers after ingestion of 2H2O and [U-13C3]propionate allowed a noninvasive profiling of hepatic gluconeogenic pathways. The method should find use in metabolic studies of infants and other populations where blood sampling is either limited or problematic.
Burgess
Shawn C
SC
The Mary Nell and Ralph B. Rogers Magnetic Resonance Center, Department of Radiology, University of Texas Southwestern Medical Center, 5801 Forest Park Road, Dallas 75235-9085, USA. shawn.burgess@utsouthwestern.edu
Weis
Brian
B
Jones
John G
JG
Smith
Erin
E
Merritt
Matthew E
ME
Margolis
David
D
Dean Sherry
A
A
Malloy
Craig R
CR
D000082:Acetaminophen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000652:urine; D000284:Administration, Oral; D000328:Adult; D002247:Carbon Isotopes / Q000097:blood / Q000652:urine*; D003903:Deuterium / Q000097:blood / Q000652:urine*; D006801:Humans; D007536:Isomerism; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011422:Propionates / Q000008:administration & dosage
D002247:Carbon Isotopes; D011422:Propionates; D000082:Acetaminophen; C037386:acetaminophen glucuronide; D003903:Deuterium