Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.15.1 (
ACE
)
18,300
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
To clarify the mechanism of production of des-gamma-carboxy (abnormal) prothrombin (
DCP
) by hepatocellular carcinoma (HCC), we measured the levels of vitamin K,
DCP
, immunoreactive prothrombin and the activity of
gamma-glutamyl carboxylase
in liver tissues from HCC patients and in the medium of cultured human hepatoma cells. There was no significant difference in vitamin K (K1, MK-4) contents between HCC and non-HCC cirrhotic liver tissues. The activity of
gamma-glutamyl carboxylase
per unit amount of endogenous microsomal prothrombin precursor was decreased in HCC tissue compared with non-HCC liver tissue (positive plasma
DCP
: 335 +/- 72 vs 372 +/- 67, negative plasma
DCP
: 370 +/- 84 vs 393 +/- 56 nmol/min per mg prothrombin precursor, P > 0.05), although the total incorporation of 14COOH into microsomal precursor protein was higher in the former. By contrast, levels of
DCP
and immunoreactive prothrombin in HCC tissue were greater (P < 0.05) than those in non-HCC cirrhotic liver tissue. Furthermore, production of large amounts of immunoreactive prothrombin was observed in human hepatoma cells huH-1 and huH-2, which produced large amounts of
DCP
. These results suggest that there was excessive synthesis of prothrombin precursors by human HCC tissue and hepatoma cell lines huH-1 and huH-2. Thus, excessive synthesis of prothrombin precursors seems to be the main mechanism of
DCP
production by HCC.
...
PMID:Levels of vitamin K, immunoreactive prothrombin, des-gamma-carboxy prothrombin and gamma-glutamyl carboxylase activity in hepatocellular carcinoma tissue. 762 Jan 13
Using
GGCX
gene-specific real-time PCR, exon 2 deletion splice variant of vitamin K-dependent
gamma-glutamyl carboxylase
(
GGCX
) mRNA was identified in HCC cell lines. Expressions of wild type and exon 2 deletion variant of
GGCX
were analyzed with relevance to
DCP
production in HCC cell lines. Hep3B, HepG2, HuH1, HuH7, and PLC/PRF/5 produced
DCP
, while SK-Hep-1, HLE, HLF, and JHH1 produced no detectable level of
DCP
.
DCP
-producing cells expressed exon 2 deletion variant of
GGCX
mRNA and protein, while
DCP
-negative cells expressed no detectable level of exon 2 deletion variant of
GGCX
. These results suggest that exon 2 deletion splice variant of
GGCX
causes dysfunction of
GGCX
enzyme activity resulting in
DCP
production in HCC cell lines.
...
PMID:Exon 2 deletion splice variant of gamma-glutamyl carboxylase causes des-gamma-carboxy prothrombin production in hepatocellular carcinoma cell lines. 1938 45
