Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0005940 (bone disease)
 7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The markedly variable clinical expressivity of hypophosphatasia was explored by examining biochemical properties of alkaline phosphatase (ALP) in fibroblasts cultured from 16 patients with severe autosomal recessive forms of this metabolic bone disease. Outcome ranged from death in utero to survival into childhood. Mean ALP activity in patients was 4.3% of controls. Gel filtration analysis indicated a mixture of dimeric and tetrameric ALP in both subject groups. Control cells produced levels of bone ALP cross-reacting material that correlated strongly with ALP activity. Patient bone ALP cross-reacting material levels averaged 41% of the control mean with a wide range of individual values that did not correlate with ALP activity. Control ALP activity was stable in 3% SDS and during electrodialysis. Patient ALP activity was generally unstable under both conditions but with a considerable range of individual values. Fibroblast ALP from every patient exhibited some aberrancy in physicochemical and immunoreactive properties. These data strongly correlated (r = 0.95) with clinical severity. There appeared to be specific associations of tissue nonspecific (bone/liver/kidney isoenzyme) ALP (TNSALP) gene mutations with aberrant enzyme properties and disease severity. We conclude that a spectrum of aberrant biochemical properties of the TNSALP enzyme, caused by different combinations of TNSALP gene missense mutations, reflects the variable clinical expressivity of hypophosphatasia.
 ...
PMID:Aberrant properties of alkaline phosphatase in patient fibroblasts correlate with clinical expressivity in severe forms of hypophosphatasia. 867 82

Alkaline phosphatase (ALP) hydrolyzes a variety of monophosphate esters into phosphoric acid and alcohol at a high optimum pH (pH 8-10). Human ALPs are classified into four types: tissue-non specific (TNSALP, liver/bone/kidney), intestinal, placental, and germ cell types. Based on studies of hypophosphatasia (HPP), which is a systemic bone disease caused by the presence of either one or two pathologic mutations in ALPL that encodes TNSALP, TNSALP was suggested to be indispensable for skeletal mineralization. In this study, we explored the possibility that dietary nutrients contribute to regulate serum bone-specific ALP (BAP) activity. Serum biochemical parameters, such as serum ALP, BAP, osteocalcin, and fibroblast growth factor 23 (FGF23), were measured in healthy young subjects (n=193). Dietary nutrient intakes were measured based on 3-d food records before the day of blood examinations. The presence of a carrier of the deletion of T at nucleotide 1559 (c.1559delT), which has been reported to be the most frequent in Japanese HPP, was not detected in any subject. By the analysis of BAP activity and other biochemical parameters or dietary nutrient intakes, we obtained significant correlations between BAP activity and serum phosphorus (r=-0.165, p=0.022), calcium intake (mg/1,000 kcal/d) (r=-0.186, p=0.010), or phosphorus intake (mg/1,000 kcal/d) (r=-0.226, p=0.002). Further study on the regulation of BAP activity and calcium and/or phosphorus homeostasis will provide useful data for improving skeletal health.
 ...
PMID:A study of the association between serum bone-specific alkaline phosphatase and serum phosphorus concentration or dietary phosphorus intake. 2341 4