Identification of genetic variants in the human indoleamine 2,3-dioxygenase (IDO1) gene, which have altered enzyme activity

2009 ◽  
Vol 19 (6) ◽  
pp. 464-476 ◽  
Author(s):  
Million Arefayene ◽  
Santosh Philips ◽  
Donghua Cao ◽  
Sudharani Mamidipalli ◽  
Zeruesenay Desta ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Genetic Variants ◽  
Indoleamine 2,3 Dioxygenase

scholarly journals Indoleamine 2,3-dioxygenase. A new, rapid, sensitive radiometric assay and its application to the study of the enzyme in rat tissues

1980 ◽  
Vol 189 (3) ◽  
pp. 461-466 ◽  
Author(s):  
J S Cook ◽  
C I Pogson ◽  
S A Smith
Keyword(s):  
Enzyme Activity ◽  
Rat Tissues ◽  
Rat Intestine ◽  
Indoleamine 2,3 Dioxygenase ◽  
Crude Extracts ◽  
Large Numbers ◽  
Kidney Enzyme ◽  
Excess Substrate ◽  
Radiometric Assay

A simple and convenient assay for indoleamine 2,3-dioxygenase has been developed. This depends on the conversion of D-[ring-2-14C]tryptophan to [14C]formate, excess substrate is removed by adsorption onto charcoal. This assay, which is 20-fold more sensitive than previous procedures, is applicable both to crude extracts and to large numbers of samples. Activity in rat tissues is very much lower than in those of the rabbit; measureable activity is found only in the stomach, spleen, intestine and kidney. Enzyme activity in the rat intestine was increased by 50% in rats pretreated with L-tryptophan.

scholarly journals The Genetics of Adverse Drug Outcomes in Type 2 Diabetes: A Systematic Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Assefa M. Baye ◽  
Teferi G. Fanta ◽  
Moneeza K. Siddiqui ◽  
Adem Y. Dawed
Keyword(s):  
Systematic Review ◽  
Type 2 Diabetes ◽  
Enzyme Activity ◽  
Adverse Effects ◽  
Genetic Variants ◽  
Cochrane Library ◽  
Oral Glucose ◽  
Concomitant Treatment ◽  
Glucose Lowering

Background: Adverse drug reactions (ADR) are a major clinical problem accounting for significant hospital admission rates, morbidity, mortality, and health care costs. One-third of people with diabetes experience at least one ADR. However, there is notable interindividual heterogeneity resulting in patient harm and unnecessary medical costs. Genomics is at the forefront of research to understand interindividual variability, and there are many genotype-drug response associations in diabetes with inconsistent findings. Here, we conducted a systematic review to comprehensively examine and synthesize the effect of genetic polymorphisms on the incidence of ADRs of oral glucose-lowering drugs in people with type 2 diabetes.Methods: A literature search was made to identify articles that included specific results of research on genetic polymorphism and adverse effects associated with oral glucose-lowering drugs. The electronic search was carried out on 3rd October 2020, through Cochrane Library, PubMed, and Web of Science using keywords and MeSH terms.Result: Eighteen articles consisting of 10, 383 subjects were included in this review. Carriers of reduced-function alleles of organic cation transporter 1 (OCT 1, encoded by SLC22A1) or reduced expression alleles of plasma membrane monoamine transporter (PMAT, encoded by SLC29A4) or serotonin transporter (SERT, encoded by SLC6A4) were associated with increased incidence of metformin-related gastrointestinal (GI) adverse effects. These effects were shown to exacerbate by concomitant treatment with gut transporter inhibiting drugs. The CYP2C9 alleles, *2 (rs1799853C>T) and *3 (rs1057910A>C) that are predictive of low enzyme activity were more common in subjects who experienced hypoglycemia after treatment with sulfonylureas. However, there was no significant association between sulfonylurea-related hypoglycemia and genetic variants in the ATP-binding cassette transporter sub-family C member 8 (ABCC8)/Potassium Inwardly Rectifying Channel Subfamily J Member 11 (KCNJ11). Compared to the wild type, the low enzyme activity C allele at CYP2C8*3 (rs1057910A>C) was associated with less weight gain whereas the C allele at rs6123045 in the NFATC2 gene was significantly associated with edema from rosiglitazone treatment.Conclusion: In spite of limited studies investigating genetics and ADR in diabetes, some convincing results are emerging. Genetic variants in genes encoding drug transporters and metabolizing enzymes are implicated in metformin-related GI adverse effects, and sulfonylurea-induced hypoglycemia, respectively. Further studies to investigate newer antidiabetic drugs such as DPP-4i, GLP-1RA, and SGLT2i are warranted. In addition, pharmacogenetic studies that account for race and ethnic differences are required.

scholarly journals Elevated indoleamine-2,3-dioxygenase enzyme activity in a novel mouse model of HIV-associated atherosclerosis

AIDS ◽  
2019 ◽  
Vol 33 (10) ◽  
pp. 1557-1564
Author(s):  
Alison C. Kearns ◽  
Stephani Velasquez ◽  
Fengming Liu ◽  
Shen Dai ◽  
Yong Chen ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Mouse Model ◽  
Indoleamine 2,3 Dioxygenase

scholarly journals Individualized Therapy: Role of Thiopurine S-Methyltransferase Protein and Genetic Variants

2010 ◽  
Vol 29 (3) ◽  
pp. 150-156 ◽  
Author(s):  
Sonja Pavlović ◽  
Branka Zukić
Keyword(s):  
Enzyme Activity ◽  
Genetic Variants ◽  
Regulatory Elements ◽  
Activity Level ◽  
Individualized Therapy ◽  
Tpmt Activity ◽  
Hematologic Toxicity ◽  
Dependent Manner ◽  
Tpmt Gene

Individualized Therapy: Role of Thiopurine S-Methyltransferase Protein and Genetic VariantsThiopurine S-methyltransferase (TPMT: EC 2.1.1.67) is an enzyme that metabolizes immunosuppressive thiopurine medications, used in the treatment of autoimmune diseases, cancer and in transplantation medicine. In some individuals, TPMT enzyme activity is significantly increased or decreased compared to the normal TPMT activity level. Structural and biochemical analyses of the TPMT protein revealed the existence of certain protein variants with altered activity. It has been shown that certain TPMT gene polymorphisms exist, that define different TPMT allozymes. Decreased TPMT enzyme activity can also be a consequence of lower protein synthesis, which depends on the promoter transcription activity. Promoter polymorphisms, such as variable number of tandem repeats (VNTR), can modulate the transcription. Administering thiopurine drugs in patients with certain genetic TPMT variants leads to severe hematologic toxicity. To avoid toxicity, therapy is being modified according to the TPMT genotype (pharmacogenetics). We investigated the polymorphisms in exons and regulatory elements (promoter) of the TPMT gene which affect TPMT enzyme activity in the Serbian population. We used PCR-based methodology and sequencing in the detection of genetic variants on TPMT gene. We showed that genetic variants in exons account for 7.5% of all TPMT variants with decreased enzyme activity. The therapy for patients with these pharmacogenetic markers was modified, which contributed to the efficiency of treatment. Functional assaysin vitroshowed that the TPMT promoter activity and, therefore, the quantity of TPMT protein synthesized, depended on the architecture of VNTRs (i.e. number and type) in the promoter. Promoter of the TPMT gene specifically responds to mercaptopurine treatment of K562 cells in a VNTR-dependent manner. Study of DNA-protein interactions revealed that Sp1 and Sp3 transcription factors interact with VNTRs. Our research pointed out that the VNTR promoter region of the TPMT gene could become a new pharmacogenetic marker, clinically significant for the individualization of thiopurine therapy.

scholarly journals PLTP activity inversely correlates with CAAD: effects of PON1 enzyme activity and genetic variants on PLTP activity

2015 ◽  
Vol 56 (7) ◽  
pp. 1351-1362 ◽  
Author(s):  
Daniel Seung Kim ◽  
Amber A. Burt ◽  
Jane E. Ranchalis ◽  
Simona Vuletic ◽  
Tomas Vaisar ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Genetic Variants ◽  
Pltp Activity

Morphological and biochemical analyses of changes in rat hepatocytes related to wine and ethanol consumption

1984 ◽  
Vol 42 ◽  
pp. 232-233
Author(s):  
S.M. Geyer ◽  
C.L. Mendenhall ◽  
J.T. Hung ◽  
E.L. Cardell ◽  
R.L. Drake ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Enzyme Activity ◽  
Malic Enzyme ◽  
Smooth Endoplasmic Reticulum ◽  
Rat Hepatocytes ◽  
Mature Male ◽  
Treatment Groups ◽  
Malic Enzyme Activity ◽  
Biochemical Analyses

Thirty-three mature male Holtzman rats were randomly placed in 3 treatment groups: Controls (C); Ethanolics (E); and Wine drinkers (W). The animals were fed synthetic diets (Lieber type) with ethanol or wine substituted isocalorically for carbohydrates in the diet of E and W groups, respectively. W received a volume of wine which provided the same gram quantity of alcohol consumed by E. The animals were sacrificed by decapitation after 6 weeks and the livers processed for quantitative triglycerides (T3), proteins, malic enzyme activity (MEA), light microscopy (LM) and electron microscopy (EM). Morphometric analysis of randomly selected LM and EM micrographs was performed to determine organellar changes in centrilobular (CV) and periportal (PV) regions of the liver. This analysis (Table 1) showed that hepatocytes from E were larger than those in C and W groups. Smooth endoplasmic reticulum decreased in E and increased in W compared to C values.

Indoleamine 2,3 dioxygenase downregulates intestinal inflammation

2001 ◽  
Vol 120 (5) ◽  
pp. A182-A182
Author(s):  
G GREGORY ◽  
W STENSON ◽  
R NEWBERRY
Keyword(s):  
Intestinal Inflammation ◽  
Indoleamine 2,3 Dioxygenase
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