Enzymes deficiency

A knowledge of normal metabohsm is essential for an understanding of abnormalities underlying disease. Normal metabolism includes adaptation to periods of starvation, exercise, pregnancy, and lactation. Abnormal metabolism may result from nutritional deficiency, enzyme deficiency, abnormal secretion of hormones, or the actions of drugs and toxins. An important example of a metabolic disease is diabetes mellitus. 

NeuAc, N-acetylneuraminic acid Cer, ceramide Gic, giucose Gai, gaiactose. -p, site of deficient enzyme reaction. 

The vast majority of hypothyroid patients have thyroid gland failure (primary hypothyroidism). The causes include chronic autoimmune thyroiditis (Hashimoto s disease), iatrogenic hypothyroidism, iodine deficiency, enzyme defects, thyroid hypoplasia, and goitrogens. 

TN was increased by the presence of the general acid. These observations suggested that H2O serves to donate the protons required to form product H2O2. Values of Km and TN for the zinc-deficient enzyme were found to be approximately a factor of two less than those obtained for the holoenzyme under identical experimental conditions, whereas TN/Xm was largely unchanged. The authors concluded that the imidazolate bridge is thus not essential for catalytically competent extraction of a proton from the solvent by CuZnSOD. 

Dimethyl-l,2,5-oxadiazolo[3,4-d]pyridazine 1,5,6-trioxide (41) is also an old product [7,11, 31] that has recently been found to react with GSH to give S-nitrosogluta-thione, NO and HNO [32]. It stimulates partially purified rat lung soluble guanylate cyclase, but not the heme-deficient enzyme. The activation is inhibited by ODQ. The product also displays significant vasodilator activity on rat thoracic aorta rings at nanomolar concentrations. Finally, [l,2,5]oxadiazolo[3,4-d]pyrimidine-5,7-dione 1-oxide derivatives (42, R,Ri=CH3,H) release NO, detected as nitrite, in the presence of thiols. A mechanism for this release has been proposed [33]. 

The number of drugs susceptible to S-methylation is still limited but greater than the number turned over by COMT. Thiopurine methyl transferase (TPMT) is an important enzyme responsible for detoxifying mercaptopurine—a drug used to treat leukemia— as well as azathioprine —a prodrug that is metabolized to mercaptopurine (Fig. 7.12). This enzyme is polymorphic and patients who are homozygous for the deficient enzyme experience severe toxicity when given usual doses of mercaptopurine (19). Similar aromatic and heterocyclic sulfhydryls can also be substrates for TPMT. The similar thiol... 

Type Deficient Enzyme Cardinal Clinical Features Glycogen Structure... 

Pseudo-Hurler polydystrophy (mucolipidosis III, ML-III) is related to l-cell disease, but cells of these patients retain some activity of the deficient enzyme. 

Ignarro, L. ]., Adams, J. B., Horwitz, P. M., and Wood, K. S. (1986a). Activation of soluble guanylate cyclase by NO-hemoproteins involves NO-heme exchange Comparison of heme-containing and heme-deficient enzyme forms. ). Biol. Chem. 261, 4997-5002. 

McCabe ER, Sadava D, Bullen WW, McKelvey HA, Seltzer WK, Rose Cl (1982) Human glycerol kinase deficiency enzyme kinetics and fibroblast hybridization. J Inherit Metab Dis... 

Oxidized, denatured hemoglobin forms aggregates, which can become attached to the inner surface of the red cell, known as Heinz bodies. This leads to damage to the red cell, which may result in direct destruction of the cell, which can be shown in vitro, or removal from the circulation by the spleen in vivo. When caused by Fava beans, the syndrome is known as Favism. As the deficient enzyme (glucose-6-phosphate dehydrogenase) is intrinsic to the red cell, exposure of such cells in vitro to suitable drugs will lead to cell damage and death. 

Thus, it has been found that genetic diseases run the gamut of time and of severity. In Pompc s disease, a deficient enzyme (alpha-1,4-glucosidasc) may range from death (total deficiency) to the progressive manifestation of cardiac or peripheral myopathy in later life (mild deficiency). 

Disease Deficient Enzyme Tentative Structure of Glycosphingolipid Accumulating in Human Skin Fibroblasts Abbreviated form of GSL... 

ACTH stimulation may distinguish three forms of "late-onset" (nonclassic) congenital adrenal hyperplasia from states of ovarian hyperandrogenism, all of which may be associated with hirsutism. In patients with deficiency of 21-hydroxylase, ACTH stimulation results in an incremental rise in plasma 17-hydroxyprogesterone, the substrate for the deficient enzyme. Patients with 11-hydroxylase deficiency manifest a rise in 11-deoxycortisol, while those with 3B-hydroxy-5 5 steroid dehydrogenase deficiency show an increase of 17-hydroxypregnenolone in response to ACTH stimulation. 

Children with any of the isolated carboxylase deficiencies do not improve with biotin supplementation, whereas those with multiple carboxylase deficiency do. A trial of biotin is often expedient and useful in discriminating between the isolated carboxylase deficiencies and the multiple carboxylase deficiencies. Isolated carboxylase deficiencies can be definitively confirmed by demonstrating deficient enzyme activity of one of three mitochondrial carboxylases in extracts of peripheral blood leukocytes (prior to biotin therapy) or cultured fibroblasts, whereas the activities of the other two carboxylases are normal. 

How does the location of the gene that encodes OTC on the X chromosome contribute to greater clinical variation in patients with deficient enzyme activity List reasons why the diagnosis of OTC deficiency is difficult in women. 

Current concepts of the chemical nature and role of molybdenum-containing enzymes are reviewed. Methods for molybdenum in enzymes, spectroscopic manifestations of the metal, and the characteristics of molybdenum-deficient enzymes are discussed, with particular attention to xanthine oxidase, sulfite oxidase, and nitrate reductase, in which Mo5 (and Mo3 in some cases) species are readily demonstrated. Nitrogenase is presumed to use molybdenum in a catalytic step, but no direct evidence for its participation in catalysis is yet available. 

Adverse effects include CNS symptoms (reversible blurring of vision, diplopia, dizziness and ataxia) and depression of cardiac AV conduction. Alimentary symptoms, skin rashes, blood disorders and liver and kidney dysfunction also occur. Osteomalacia by enhanced metabolism of vitamin D (enzyme induction) occurs over years so also does folate deficiency. Enzyme induction reduces the efficacy of combined and progestogen-only contraceptives. Carbamazepine impairs cognitive function less than phenytoin. 

Other vehicles for enzyme replacement in deficiency diseases might include transfusion of cells loaded with the deficient enzyme or whole tissues (e.g. kidney). A major problem in all of these approaches will be the exclusive delivery of the "cure"-containing vehicles to the proper target site. This presumably will await modeling of the vehicle in such a way as to permit its recognition (via specific receptors) and ingestion by... 

Glucose-6-P Deficient enzyme of Hemolytic anemia with... 

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