Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.109 (AST)
 6,066 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To test further the competence of the cirrhotic liver to metabolize vitamin D3 at C-25, hepatocytes were isolated from controls and from CCl4-induced cirrhotic rat livers, as well as from partially hepatectomized rats. The transformation of D3 into 25-hydroxyvitamin D3 was studied in the presence of 10(7) hepatocytes at D3 concentrations of 20 nmol/L to 15.4 mumol/L. Histologically, micronodular cirrhosis was present in all CCl4-treated rats, whereas controls had normal livers; portal venous pressure (p less than 0.008) and intrahepatic collagen content (p less than 0.0001) were significantly increased in CCl4-treated rats, whereas no difference was found between the two groups in the total and ionized serum calcium, D3 metabolites, ALT, AST and alkaline phosphatase. Cytochrome P-450 was 0.27 +/- 0.02 and 0.25 +/- 0.02 nmol/10(6) hepatocytes in controls and cirrhotic rats (N.S.), and it significantly increased in both groups after phenobarbital or 3-methylcholanthrene administration (p less than 0.0001). 25-Hydroxyvitamin D3 formation was best described by power law equations and varied between 0.02 +/- 0.0004 and 29.57 +/- 2.8 in controls, and 0.024 +/- 0.0004 and 32.0 +/- 7.0 pmol.hr-1.10(6) hepatocytes-1 in cirrhotic rats. No statistically significant difference was found in the slopes of the 25-hydroxyvitamin D3 formation, but the y-axis intercept was found to be lower in cirrhotic rats under basal resting conditions (p less than 0.005). Inducers of the mixed function oxidases significantly increased 25-hydroxyvitamin D3 formation in controls as well as in cirrhotic rats (p less than 0.005). Moreover, both groups were found to respond similarly to the addition of modulators of the enzyme such as the calcium ionophore A23187 and parathyroid hormone. Partial hepatectomy was also without effect on the activation of D3. Furthermore, the cell sequestration of D3 was also found to be unperturbed in hepatocytes obtained from either cirrhotic or partially hepatectomized livers. The data indicate that in well-compensated micronodular cirrhosis, the C-25 hydroxylation of D3 is generally intrinsically normal at the cellular level and that it also remains fully responsive to in vivo and in vitro modulators of its activity.
 ...
PMID:In micronodular cirrhosis, hepatocytes retain a normal C-25 hydroxylation capacity toward vitamin D3: a study using the rat carbon tetrachloride-induced cirrhotic model. 184 94

To determine the effect of life-long alcohol consumption on the adult and aged rat model, 4-week-old, female Sprague-Dawley rats were divided into three diet groups. Alcohol-treated animals were fed a modified Lieber-DeCarli diet ad libitum containing 35% ethanol-derived calories, whereas the pair-fed animals (weight-matched to ethanol rats) received an isocaloric liquid diet in which maltose-dextrin substituted calories supplied by ethanol. Chow animals were fed a standard rat chow ad libitum. Proximal tibiae (primarily cancellous bone) and femora (primarily cortical bone) were removed for analysis after 3, 6, 9, 12, or 18 months on the diets. Serum was collected for analysis of calcium levels, the calcium regulating hormones; parathyroid hormone, 25-hydroxyvitamin D, calcitonin, corticosterone, estradiol, testosterone, and IGF-1. Creatinine, SGOT/AST, and SGPT/ALT levels were measured to determine kidney and liver integrity. Previous studies, with young animals, showed that chronic alcohol consumption during the age of bone development reduced bone density and bone mass in both cortical and cancellous bone. The present study demonstrates that these reductions last throughout life, whereas morphological values, such as length and diameter, attain control levels. Calcium regulating hormones and sex hormones are essentially normal and do not appear to be the primary causative agent for adult alcohol-induced osteopenia, but it appears to be due to a more direct effect of alcohol on bone cells.
 ...
PMID:Effect of alcohol consumption on adult and aged bone: composition, morphology, and hormone levels of a rat animal model. 1047 Sep 86

We have examined the relationship between self-reported alcohol intake (SRAI), season and mineral metabolism in a series of 96 men aged 32 to 78 years of age. Alcohol intake was reported as between 0 and 50 oz/week. SRAI correlated positively with liver function tests, including serum bilirubin, alkaline phosphatase, and AST initially and at 6 months. In addition, SRAI correlated with serum calcium, testosterone, estradiol, and immunoreactive parathyroid hormone (iPTH) as well as urinary calcium [per 100 mg of creatinine (Cr)], and pyridinoline crosslinks (DPC) (per 100 mg of Cr). We have divided the participants into two groups on the basis of their reported alcohol intake. Individuals with none-to-moderate intake had <8.4 oz/week of ethanol. Those with moderate or heavier intake had 8.4 oz or more of ethanol/week. Individuals with none-to-moderate SRAI had a significant seasonal increase in iPTH, osteocalcin, urine DPC/100 mg of Cr and a decrease in distal forearm bone mineral density, 25 hydroxyvitamin D (250HD), and urinary calcium/100 mg of Cr. Individuals with moderate or heavier SRAI only had significant seasonal decrease in 250HD. We have concluded that alcohol intake decreases seasonal change in serum iPTH. The biological effects of such alterations in parathyroid hormone levels include decreased seasonal loss of bone mineral density.
 ...
PMID:The effects of season and alcohol intake on mineral metabolism in men. 1006 48

Protein-energy malnutrition and inflammation are among the leading causes of poor outcome in hemodialysis patients. Hepatitis C virus (HCV) infection is accompanied by elevated proinflammatory mediators, also found in dialysis patients with malnutrition-inflammation complex syndrome. We aimed to study the rate and characteristics of malnutrition-inflammation complex syndrome (MICS) in hemodialysis patients, especially those with hepatitis C. The study included 147 patients (mean age 55.1 +/- 12.9 years), 24.5% of whom were HCV-positive, undergoing adequate hemodialysis three times a week for the last 52.7 +/- 52.5 months. Parameters of nutrition and inflammation were investigated to evaluate MICS. HCV-positive vs. HCV-negative patients had significantly higher hematocrit (29.6 +/- 4.5 g/dL vs. 28.1 +/- 4.3, P < 0.05), uric acid (345.8 +/- 96.5 vs. 321.3 +/- 118.8 micromol/mL, P < 0.05), aspartate aminotransferase (AST, also known as serum glutamic oxaloacetic transaminase [SGOT]) (23.3 +/- 14.9 vs. 17.8 +/- 9 U/L, P < 0.008), alanine aminotransferase (ALT, also known as serum glutamic pyruvic transaminase [SGPT]) (41.2 +/- 28.7 vs. 26.6 +/- 17.1 U/L, P < 0.0003), serum creatinine (980.4 +/- 219.1 vs. 888.4 +/- 202.9 micromol/mL, P < 0.022), intact parathyroid hormone (329.7 +/- 630.5 vs. 110.2 +/- 145.3 pg/mL, P < 0.002), malnutrition-inflammation score (7.4 +/- 5.2 vs. 5.6 +/- 4.1, P < 0.038), and Charlson comorbidity index (4.5 +/- 1.5 vs. 4 +/- 1.4, P < 0.05). MICS had a prevalence of 20-40% in our study. HCV-positive patients had a significantly higher prevalence of MICS than HCV-negative patients (30-40% vs. 20-30%).
 ...
PMID:Malnutrition-inflammation complex syndrome and hepatitis C in maintenance hemodialysis patients. 1937 50

Patients with chronic kidney disease (CKD), especially those on dialysis treatment, are at high risk of bone fracture. In CKD-mineral and bone disorder (CKD-MBD), secondary hyperparathyroidism in patients with advanced CKD induces bone abnormalities, and skeletal resistance to parathyroid hormone (PTH) starts in the early stages of kidney disease. Uremic toxins such as indoxyl sulfate and p-cresyl sulfate reduce the expression of PTH receptor as well as PTH-induced cyclic adenosine 3',5' monophosphate production in osteoblasts. CKD also impairs bone strength, especially quality. In a rat model, kidney damage reduces the bone-storage modulus and changes the cortical bone chemical composition with or without hyperparathyroidism. The oral charcoal adsorbent AST-120 improves CKD-induced bone abnormalities as blood levels of indoxyl sulfate decrease. Uremic osteoporosis, a new concept of CKD-related bone fragility, is a main cause of CKD-induced bone abnormalities, particularly impaired bone quality. There is limited information about the effect and safety of anti-osteoporotic drugs for patients with CKD, especially those on dialysis, but the use of AST-120 and renin-angiotensin system inhibitors may modulate bone quality and decrease the incidence of fracture. Thus, the management of CKD-MBD plus use of other therapeutic interventions for uremic osteoporosis is necessary to prevent bone fragility in patients with CKD.
 ...
PMID:Uremic Toxicity and Bone in CKD. 2857 86