Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.4.3.13 (lysyl oxidase)
 1,248 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Impaired bone quality has been proposed as a cause of increased bone fragility in osteoporosis. Collagen crosslinking is a candidate for determining the material properties of bone. Collagen cross-links are of two types; lysyl oxidase (LOX) and lysyl hydroxylase (PLOD1; LH1, PLOD2; LH2b) controlled cross-links, and advanced glycation end products, pentosidine. Homocysteine and vitamin B(6) (pyridoxal) are also regulatory factors of collagen crosslinking. Recently, we reported that in the femoral neck fracture cases, not only reduced enzymatic cross-links in old osteon and increased pentosidine in both young and old osteons from cortical and cancellous bone, but also higher plasma homocysteine and lower pyridoxal levels were evident compared with the controls (Osteoporos Int 2006. Calcif Tissue Int, 2006). In this review, we describe that mildly hyperhomocysteinemia, and vitamin B(6) or vitamin D insufficiency are crucial determinants of detrimental crosslinking of bone collagen in patients with hip fracture.
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PMID:[Elevated plasma concentration of homocysteine, low level of vitamin B6, pyridoxal, and vitamin D insufficiency in patients with hip fracture: a possible explanation for detrimental cross-link pattern in bone collagen]. 1714 27

Bone quality is thought to encompass the structural and material properties of bone that are affected by turnover rate. The concept of bone quality is included in Japanese Guideline for Osteoporosis prevention and treatment. Evidence has accumulated that collagen cross-links play important roles in bone strength. We have demonstrated that the quantitative and qualitative deterioration of lysyl oxidase controlled and non-enzymatic cross-links (Advanced glycation end products, AGEs, Pentosidine) of collagen in patients with osteoporotic femoral neck fracture cases might be affected by hyperhomocysteinemia (Saito M, Calcif Tissue Int, 2006), oxidative stress, vitamin B status (Saito M, Osteoporos Int, 2006) . Recently, Shiraki et al. demonstrated that a functional polymorphism in methylenetetrahydrofolate reductase (MTHFR) polymorphism, T allele (C677T), may be a risk factor for future fracture in addition to the traditional risk factors (Shiraki M, Saito M, et al., J Bone Miner Metab, in press). In addition, we have reported that a higher urinary pentosidine was an independent risk factor, for vertebral fracture in a 5-year prospective study in Japanese women (Shiraki M, Saito M, et al., J Bone Miner Metab, 2008). If confirmed in large, prospective trials, measurement of serum homocysteine and serum or urinary excretion of pentosidine might be characterized as markers reflecting bone collagen deterioration.
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PMID:[Daily practice using the guidelines for prevention and treatment of osteoporosis. How do we realize the bone quality in routine practice using Japanese guideline for osteoporosis prevention and treatment?]. 1867 47

Elevated levels of homocysteine (Hcy) (known as hyperhomocysteinemia HHcy) are involved in dilated cardiomyopathy. Hcy chelates copper and impairs copper-dependent enzymes. Copper deficiency has been linked to cardiovascular disease. We tested the hypothesis that copper supplement regresses left ventricular hypertrophy (LVH), fibrosis and endothelial dysfunction in pressure overload DCM mice hearts. The mice were grouped as sham, sham + Cu, aortic constriction (AC), and AC + Cu. Aortic constriction was performed by transverse aortic constriction. The mice were treated with or without 20 mg/kg copper supplement in the diet for 12 weeks. The cardiac function was assessed by echocardiography and electrocardiography. The matrix remodeling was assessed by measuring matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinases (TIMPs), and lysyl oxidase (LOX) by Western blot analyses. The results suggest that in AC mice, cardiac function was improved with copper supplement. TIMP-1 levels decreased in AC and were normalized in AC + Cu. Although MMP-9, TIMP-3, and LOX activity increased in AC and returned to baseline value in AC + Cu, copper supplement showed no significant effect on TIMP-4 activity after pressure overload. In conclusion, our data suggest that copper supplement helps improve cardiac function in a pressure overload dilated cardiomyopathic heart.
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PMID:Role of copper and homocysteine in pressure overload heart failure. 1867 30

Bone quality is thought to encompass the structural and material properties of bone that are affected by the turnover rate. Evidence has accumulated that collagen cross-links play important roles in bone strength. We have demonstrated that the quantitative and qualitative deterioration of lysyl oxidase control and non enzymatic cross-links (advanced glycation end products, AGEs, pentosidine) of collagen in patients with osteoporotic femoral neck fracture might be affected by hyperhomocysteinemia, oxidative stress, and vitamin B6 insufficiency. Recently, Shiraki et al. demonstrated that a functional polymorphism in methylenetetrahydrofolate reductase (MTHFR) polymorphism, T allele (C677T), may be a risk factor for future fracture in addition to the traditional risk factors. Further, we reported that a higher urinary pentosidine level was an independent risk factor for vertebral fracture in a 5-year prospective study involving Japanese women. If confirmed in large, prospective trials, measurements of serum homocysteine and serum or urine levels of pentosidine might be characterized as markers reflecting bone collagen deterioration.
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PMID:[Bone quality markers: pentosidine, homocysteine, and MTHFR polymorphism]. 1986 Feb 14

Homocysteine (Hcy) is a derived sulfur-containing and non-proteinogenic amino acid. The metabolism of Hcy occurs either through the remethylation to methionine or transsulfuration to cysteine. Studies have identified hyperhomocysteinemia (HHcy) as one of the possible risk factors for a multitude of diseases including vascular, neurodegenerative and ocular diseases. Association of HHcy with eye diseases such as retinopathy, pseudoexfoliative glaucoma maculopathy, cataract, optic atrophy and retinal vessel atherosclerosis is established. The molecular mechanism underlying these ocular diseases has been reported as impaired vascular endothelial function, apoptosis of retinal ganglion cells, extracellular matrix alterations, decreased lysyl oxidase activity and oxidative stress. The formed homocysteine-thiolactone in HHcy has stronger cytotoxicity and pro-inflammatory properties which can induce lens opacification and optic nerve damage. The metabolism of Hcy requires enzymes with vitamins such as folic acid, vitamins B12 and B6. Despite the mixed conclusion of various studies regarding the level of these vitamins in elder people, studies recommended the treatment with folate and B12 to reduce Hcy levels in subjects with or without any defect in the enzymes involved in its metabolism. The levels of Hcy, folate, B6 as well as B12 should be measured early in patients with visual impairment that would aid to screen patients for life-threatening disorders related with HHcy. Elder patients may supplement with these vitamins in order to attenuate the ocular damages. This article discusses the association of Hcy in ocular diseases and the possible mechanism in the pathogenesis.
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PMID:Homocysteine in ocular diseases. 2634 24