2005 Fiscal Year Final Research Report Summary
Research and Development of Liver Cytochrome p-450 Function Inspection Medicine by a ^<13>C-Breath Test
| Project/Area Number |
15590142
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Medical pharmacy
|
|---|
| Research Institution | Meiji Pharmaceutical University |
|---|
Principal Investigator |
KAJIWARA Masahiro Meiji Pharmaceutical University, Department of Medicinal Chemistry, Professor, 薬学部・薬品化学教室, 教授 (90161041)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAKATORI Kazuhiko Meiji Pharmaceutical University, Department of Medicinal Chemistry, Lecturer, 薬学部・薬品化学教室, 講師 (30231393)
|
|---|
| Project Period (FY) |
2003 – 2005
|
| Keywords | Synthesis of ^<13>C-Amino acid / ^<13>C-Breath Test / Cytochrome p-450 / ^<13>CO_2 / ^<13>CO_2 / ^<12>CO_2 Ratio / Breath MS / Stable Isotope / Liver Function |
|---|
| Research Abstract |
_L-[3^<-13>C]Alanine, _L-[3-^<13>C]phenylalanine, _L-[3-^<13>C]tyrosine, _L-[2-^<13>C]aspartic acid, and _L-[4-^<13>C]lysine, _L-[4-^<13>C]glutamic acid, _L-[4-^<13>C]glutamine, _L-[3-^<13>C]triptophan, _L-[5'-^<13>C] and _L-[6'-^<13>C]triptophan were synthesized using Dellaria's oxazinone, prepared from phenylbromoacetate and (S)-2-phenylglycinol, as achiral glycine equivalent. Alkylation of the oxazinone with [^<13>C]alkyl halide or the [^<13>C] oxazinone with alkyl halide was achieved with high diastereoselectivity. Hydrolysis and removal of chiral auxiliary of the alkylated oxazinone gave a variety of _L-[^<13>C]amino acid.
Liver disease is associated with an abnormal elevation of the plasma concentrations of the aromatic amino acids phenylalanine and tyrosine. The liver is the main site of aromatic acid metabolism, particularly the hydroxylation of phenylalanine to tyrosine and further degradation. We have examined the usefulness of the _L-[1-^<13>C]phenylalanine breath test and _L-[1-^<13>C]tyrosine breath test for the detection of hepatic damage in patients with liver cirrhosis. First, the time course of ^<13>CO_2 excretion after the administration of _L-[1-^<13>C]phenylalanine and _L-[1-^<13>C]tyrosine were compared. The peak times were 20 min. in both breath test, but _L-[1-^<13>C]tyrosine breath test gave a higher peak than _L-[1-^<13>C]phenylalanine breath test. Next the parameter of _L-[1-^<13>C]phenylalanine breath test and _L-[1-^<13>C]tyrosine breath test were compared with biochemical liver function test values. These parameters were well correlated with several liver blood test values conventionally regarded as measures of hepatocyte reserve. Therefore, _L-[1-^<13>C]phenylalanine breath test and _L-[1-^<13>C]tyrosine breath test may be useful to assess the degree and progression of hepatic dysfunctions.
|
-
-
-
-
-
-
-
-
[Journal Article] ^1H, ^<13>C and ^<15>N Backbone Resonance Assignments of the Hyaluronan-binding Domain of CD442004
Author(s)
Takeda, M., Terasawa, H., Sakakura, M., Yamaguchi, Y., Kajiwara, M., Kawashima, H., Miyasaka, M., Shimada, I.
-
Journal Title
J.Biomol.NMR 29
Pages: 97-98
Description
「研究成果報告書概要(欧文)」より
-
-
-
[Journal Article] In Vivo Studies of Phenylalanine Hydroxylase by Phenylalanine Breath Test: Diagnosis of Tetrahydrobiopterin-responsive Phenylalanine Hydroxylase Deficiency2004
Author(s)
Okanao, Y., Hase, Y., Kawajiri, M., Nishi, Y., Inui, K., Sakai, N., Tanaka, K., Takatori, K., Kajiwara, M., Yamano, T.
-
Journal Title
Pediatr.Res. 56
Pages: 714-719
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
[Journal Article] Solid-Supported Robinson Annulation under Microwave Irradiation2003
Author(s)
Takatori, K., Nakayama, M., Futaishi, N., Yamada, S., Hirayama, S., Kajiwara, M.
-
Journal Title
Chem.Pharm.Bull. 51
Pages: 455-457
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Hyaluronan Recognition Mode of CD44 Revealed by Cross-saturation and Chemical Shift Perturbation Experiments2003
Author(s)
Takeda, M., Terasawa, H., Sakakura, M., Yamaguchi, Y., Kajiwara, M., Kawashima, H., Miyasaka, M., Shimada, I.
-
Journal Title
J.Biol.Chem. 278
Pages: 43550-43555
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
