An elevated level of total homocysteine (tHcy) in blood, denoted hyperhomocysteinemia, is emerging as a prevalent and strong risk factor for atherosclerotic vascular disease in the coronary, cerebral, and peripheral vessels, and for arterial and venous thromboembolism. The basis for these conclusions is data from about 80 clinical and epidemiological studies including more than 10,000 patients. Elevated tHcy confers a graded risk with no threshold, is independent of but may enhance the effect of the conventional risk factors, and seems to be a particularly strong predictor of cardiovascular mortality. Hyperhomocysteinemia is attributed to commonly occurring genetic and acquired factors including deficiencies of folate and vitamin B12. Supplementation with B-vitamins, in particular with folic acid, is an efficient, safe, and inexpensive means to reduce an elevated tHcy level. Studies are now in progress to establish whether such therapy will reduce cardiovascular risk.

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Homocysteine and Cardiovascular Disease

The biology of platelet-derived growth factor

NDiviDuAI with homocystinuria 12 have been found to lack normal activity of the enzyme cystathionine synthetase.3 In many of the patients progressive arterial disease develops in ildhood, frequently resulting in death from thrombosis in a vital organ45 In addition, congenital dislocation of the lenses, mental retardation, and skeletal abnormalitieseg, osteoporosis, arachnodactyly, and pectus excavatum or pectus carinatum-usually are foundL5' The vascular changes and other abnormalities encoumtered in homocystinuria have been attributed either to the metabolic effects of the elevated tissue concentrations of methionine, homocysteine, or homocystine, or to the metabolic consequences of decreased tissue concentrations of cystathionine found in the disease.7 In a child dying with homocystinuria, cystathioninuria, and methyl malonic aciduria, secondary to an abnormality of cobalamin (B12 ) metabolism, arterial lesions have been discovered that resemble in a striking way many of those found in cystathionine synthetase deficiency. The vascular findigs i this patient will be presented and compared with those in a patient with cystathionine synthetase deficiency. Since the enzymatic abnormalities in both disorders share certain metabolic consequences, the conclusion has been reached that an elevated concentration of homocysteine, homocystine, or a derivative of hornocysteine is the common factor leading to arterial damage. The possible role of elevated concentrations of homocysteine or its derivatives in the pathogenesis of arteriosclerosis in individls free of known enzyme deficiencies will be discussed and interpreted with particular reference to the findings in experimentally produced arteriosclerosis.

Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis.

The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase

Because of the high catalytic activities and substrate specificity, natural enzymes have been widely used in industrial, medical, and biological fields, etc. Although promising, they often suffer from intrinsic shortcomings such as high cost, low operational stability, and difficulties of recycling. To overcome these shortcomings, researchers have been devoted to the exploration of artificial enzyme mimics for a long time. Since the discovery of ferromagnetic nanoparticles with intrinsic horseradish peroxidase-like activity in 2007, a large amount of studies on nanozymes have been constantly emerging in the next decade. Nanozymes are one kind of nanomaterials with enzymatic catalytic properties. Compared with natural enzymes, nanozymes have the advantages such as low cost, high stability and durability, which have been widely used in industrial, medical, and biological fields. A thorough understanding of the possible catalytic mechanisms will contribute to the development of novel and high-efficient nanozymes, and the rational regulations of the activities of nanozymes are of great significance. In this review, we systematically introduce the classification, catalytic mechanism, activity regulation as well as recent research progress of nanozymes in the field of biosensing, environmental protection, and disease treatments, etc. in the past years. We also propose the current challenges of nanozymes as well as their future research focus. We anticipate this review may be of significance for the field to understand the properties of nanozymes and the development of novel nanomaterials with enzyme mimicking activities.

Nanozymes: Classification, Catalytic Mechanisms, Activity Regulation, and Applications

FABRY'S disease is a hereditary systemic disorder that was first recognized in affected males as a disease characterized by multiple small dark-purple macules and papules in the umbilical region, s...

Enzymatic defect in Fabry's disease. Ceramidetrihexosidase deficiency.

A deficiency, or absence, of cystathionine synthetase activity has been demonstrated in liver obtained from a mentally retarded child with homocystinuria.

https://science.sciencemag.org/content/sci/143/3613/1443.full.pdf

Homocystinuria: an enzymatic defect.

The enzymatic spectrophotometric method for determination of uric acid.

If-primary gout is an \"inborn error of metabolism,\" as has been postulated (1), all patients might be expected to share a common, underlying defect to account for their hyperuricemia. Disagreement has centered about the problem of whether the primary derangement involves an impairment of urate disposition or an acceleration of urate biosynthesis. In the past a variety of methods has been employed to' assess urate biosynthesis and disposition in -gouty patients. The 'daily excretion of uric acid in the urine is a convenient parameter to measure but does not include that portion of urate production which is destroyed by uricolysis or is deposited in tophi in gouty patients. Benedict, Forsham and Stetten (2) and Bishop, Garner and Talbott (3) used uric acid-N15 to estimate the magnitude of the body urate pool and its rate of turnover. Benedict and co-workers observed that, in those gouty patients with extensive tophi and greatly 'expanded urate pools, such data may not provide a valid measure of urate synthesis, since uric acid from tophaceous deposits may dilute the administered isotopically labeled urate in a manner indistinguishable from that of newly synthesized uric acid. Urate biosynthesis has also been studied by measuring the extent of incorporation of an isotopically labeled precursor into urinary uric acid. Some, though not all, of the gouty subjects studied were found to incorporate excessive amounts of glycine-N'5 into urinary uric acid (4, 5). When trace amounts of glycine-1-C14 were used in similar studies, an excessive incorporation of isotope into urinary uric acid was found in all of the six gouty subjects first investigated (6), but subsequent studies showed that there were some gouty patients in whom excessive incorporation of glycine-1-C4 into uric acid could not be detected (7-9). An excessive production of uric acid could exist in such gouty patients, yet fail to be reflected in the extent of glycine incorporation into urinary uric acid because of enhanced extrarenal disposal of urate through deposition in tophi or increased uricolysis The purpose of the present investigation was to evaluate urate production in gouty subjects in a manner that would allow corrections to be made for the extra-renal disposal of urate. Studies were performed with isotopically labeled glycine to evaluate purine synthesis and isotopically labeled uric acid to evaluate the dynamics of the urate pool. The determination of the urate pool turnover provided an independent estimate of uric acid biosynthesis. The results obtained wer'e correlated with clinical features of the disease and with urinary excretion of uric acid. On the basis of these studies, some conclusions were drawn regarding the relative roles of excessive urate production and impaired urate disposition in the pathogenesis of the hyperuricemia of gout.

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Uric acid production in gout

An infant who died with neurological abnormalities, mental retardation, and dislocated ocular lenses excreted in his urine abnormally large amounts of S-sulfo-L-cysteine, sulfite, and thiosulfate and virtulally no inorganic sutlfate. The present report establishes the occurrence of an ezymatic defect in this infant. His liver, brain, and kidney specifically lacked sulfite oxidase activity. Deficiency of sulfite oxidase, which has not apparently been described in man, provides a reasonable explanation for the abnormalities in this infant.

Leonard Laster

Papers

Enzymatic defect in Fabry's disease. Ceramidetrihexosidase deficiency.

Homocystinuria: an enzymatic defect.

The enzymatic spectrophotometric method for determination of uric acid.

Uric acid production in gout

Sulfite Oxidase Deficiency in Man: Demonstration of the Enzymatic Defect