Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.44 (AGT)
 770 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

THE FOREIGN LESION: The mechanistic questions for DNA base damage detection by repair proteins are discussed in this Minireview. Repair proteins could either probe and locate a weakened base pair that results from base damage, or passively capture an extrahelical base lesion in the first step of damage searching on double-stranded DNA. How some repair proteins, such as AGT (see figure), locate base lesions in DNA is still not fully understood.To remove a few damaged bases efficiently from the context of the entire genome, the DNA base repair proteins rely on remarkably specific detection mechanisms to locate base lesions. This efficient molecular recognition event inside cells has been extensively studied with various structural and biochemical tools. These studies suggest that DNA base damage can be located by repair proteins by using two mechanisms: a repair protein can probe and detect a weakened base pair that results from mutagenic or cytotoxic base damage; alternatively, a protein can passively capture and stabilize an extrahelical base lesion. Our chemical and structural studies on the direct DNA repair proteins hAGT, C-Ada and ABH2 suggest that these proteins search for weakened base pairs in their first step of damage searching. We have also discovered a very unique base-flipping mechanism used by the DNA repair protein AlkB. This protein distorts DNA and favors single stranded DNA (ssDNA) substrates over double-stranded (dsDNA) ones. Potentially, it locates base lesions in dsDNA by imposing a constraint that targets less rigid regions of the duplex DNA. The exact mechanism of how AlkB and related proteins search for damage in ssDNA and dsDNA still awaits further studies.
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PMID:Damage detection and base flipping in direct DNA alkylation repair. 1914 6

Renal stone disease may ensue from either derangements of urine biochemistries or anatomic abnormalities of kidneys and urinary tract. Genetic, environmental and dietary factors may also cooperate in the pathophysiology of nephrolithiasis. An adequate metabolic evaluation should focus on the urinary excretion of promoters and inhibitors of stone formation as well as on the occurrence of systemic diseases potentially related to secondary nephrolithiasis (i.e., endocrine disturbances, malabsorption, bone diseases). Moreover, metabolic investigations should provide reliable information on patient's dietary habits, guide towards the best therapeutic approach and enable the physician to verify patient's compliance to prescribed therapies.AN EXTENSIVE METABOLIC EVALUATION IS RECOMMENDED IN PATIENTS WITH ACTIVE STONE DISEASE (NAMELY, AT LEAST ONE NEW STONE WITHIN THE LAST TWO YEARS), OR IN THOSE HAVING HAD A SINGLE STONE EPISODE OCCURRED IN PECULIAR CONDITIONS: familial history of disease, childhood, menopause, pregnancy, systemic diseases. Simplified protocols may be adequate in non-active nephrolithiasis or in patients with single stone and no relevant risk factors.In our Stone Centre, a so-called "first level screening" is performed by routine, in order to assess urinary supersaturation with stone forming salts and evaluate the excretion of dietary-related metabolites in urine. Relative blood and urine determinations are reported below.IN VENOUS BLOOD: urea, creatinine, uric acid, Na, K, total and ionised Ca, Mg, P, Cl, alkaline phosphatase, gas analysis. In 24-hr urine samples: urea, creatinine, uric acid, Na, K, Ca, Mg, P, Cl, oxalate, inorganic sulphate, citrate, pH, ammonia and titratable acidity. IN FASTING URINE SAMPLES: Ca, citrate, creatinine, hydroxyproline, Brand's test for cistinuria, urine sediment, urine culture. If the first-level evaluation suggested an abnormal bone turnover, then further determinations are warranted, namely, calciotropic hormones (blood Vitamin D and PTH), markers of bone resorption (urine pyridinium crosslinks, serum crosslaps) and formation (serum osteocalcin) bone mineral density.EVENTUALLY, MORE SOPHISTICATED INVESTIGATIONS ARE REQUIRED TO IMPROVE THE DIAGNOSIS OF PECULIAR DISEASES: serum oxalate and glycolate, urine glycolate and L-glycerate, hepatic AGT activity (primary hyperoxalurias); genetic tests (hereditary nephrolithiasis); acidification tests (renal tubular acidosis).
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PMID:Biochemical evaluation in renal stone disease. 2246 Sep 94