Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activities of pyruvate decarboxylase (PDC), alpha-ketoglutarate decarboxylase (KGDC) and both the pyruvate and alpha-ketoglutarate dehydrogenase complexes (PDH complex and KGDH complex) were measured, and kinetic properties of PDC were studied in fibroblasts derived from normal individuals and from a 2-yr-old girl with congenital lactic acidemia and severe retardation of growth and development. The activities of PDC, KGDC, PDH complex, and KGDH complex in the patient were 1.12 +/- 0.12, 2.33 +/- 0.42, 9.00 +/- 0.50, and 16.46 +/- 1.57 and in controls 3.10 +/- 0.16, 5.36 +/- 0.56, 24.13 +/- 1.61 and 44.95 +/- 3.72 nmole/mg protein/hr. The optimum pH (6.0) and Michaelis constants (Km) for pyruvate of PDC (1.0-1.6 X 10(-5) M) were similar in fibroblasts of the patient and controls. PDC activity was more sensitive to denaturation by heat in the fibroblasts of the patient than those from controls, while heat denaturation curves of KGDC were similar in the patient and control. Higher concentrations of thiamine pyrophosphate (TPP) were required to protect PDC from heat denaturation in the patient. TPP was more easily removed from PDC in the patient than in the control by washing the fibroblasts with alkaline buffer. These results suggest that the PDC enzyme of the patient is in an altered molecular form, to which TPP is loosely bound. This particular constellation of abnormalities has not previously been reported in patients with lactic acidemia.
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PMID:Abnormal pyruvate and alpha-ketoglutarate dehydrogenase complexes in a patient with lactic acidemia. 48 67

The content of the Krebs cycle substrates and activity of dehydrogenases corresponding to them were studied in the brain and myocardium tissues of the non-linear male rats adapted to acute hypoxia under conditions of the altered gas medium. The content of malate and succinic acid was studied in the liver and skeletal muscles only. In the brain the total activity of malate dehydrogenase (MDH, EC 1.1.1.37, 1.1.1.39) alpha-ketoglutarate dehydrogenase (KDH, EC 1.2.4.2) pyruvate dehydrogenase (PDH, EC 1.2.4.1) and isocitrate dehydrogenase (ICDH, EC 1.1.1.41-42) is shown to be decreased and kept to be lowered in all the periods of the study. No essential shifts in the activity of these dehydrogenases were found in the myocardium. The activity of succinate dehydrogenase (SDH, EC 1.3.99.1) in both tissues lowers 48 h after the effect of the mentioned factors. Simultaneously the greatest changes in the level of the substrates were observed in the myocardium, in the brain they were less developed. In the liver the content of malate increases without pronounced changes in the amount of succinic acid and in the skeletal muscles the level of malate and succinic acid lowers.
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PMID:[Krebs cycle in tissue of rats subjected to combined effect of hypercapnia, hypoxia and cooling]. 121 51

Autoantibodies are important diagnostic markers for autoimmune type chronic active hepatitis (AI-CAH) and primary biliary cirrhosis (PBC). At least three subgroups of AI-CAH can be distinguished serologically. Antinuclear antibodies (ANA), smooth muscle antibodies (SMA), and liver membrane autoantibodies (LMA) characterize classical autoimmune type 'lupoid' hepatitis, while liver kidney microsomal (LKM) antibodies identify a second, and antibodies to a soluble liver antigen (anti-SLA), a third subgroup of AI-CAH. Patients with autoimmune type CAH in contrast to patients with virus-induced liver diseases profit from immunosuppressive therapy. PBC is characterized by disease-specific subtypes of antimitochondrial antibodies (AMA). Technical developments, like immunoblotting and molecular cloning, led to a better definition and characterization of autoantibody-antigen systems. Molecular cloning has been successfully applied to identify the main 70 kDa mitochondrial antigen in PBC. This and other mitochondrial autoantigens have been identified as enzymes: E2 component of pyruvate dehydrogenase (PDH-E2) and its component X, branched chain alpha-keto acid dehydrogenase (BCKD-E2), and 2-oxoglutarate dehydrogenase. LKM-1 antigen has been identified as cytochrome P-450 db1, a drug metabolizing enzyme with a known genetic polymorphism. These cloned hepatic autoantigens share some characteristics with other autoantigens: they are enzymes, autoantibodies react with active sites of these enzymes and the autoepitopes are highly conserved. After the identification of these autoepitopes, specific and sensitive diagnostic reagents will become available. B and T cell epitope mapping will help to elucidate whether these autoantibodies are just clinically valuable diagnostic markers or whether they contribute to the immunopathogenesis or help to identify the aetiological agents.
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PMID:Autoantibodies and antigens in liver diseases--updated. 268 96

Broiler chickens (Gallus gallus) genetically selected for rapid growth are inherently predisposed to heart failure. In order to understand the biochemical mechanisms associated with the deterioration of heart function and development of congestive heart failure (CHF) in fast-growing chickens, this study examined several factors critical for myocardial energy metabolism. Measured variables included cardiac energy substrates [creatine phosphate (CrP), adenosine triphosphate (ATP), l-carnitine], activity of selected cytosolic enzymes [creatine kinase (CK; EC 2.7.3.2), lactate dehydrogenase (LDH; EC 1.1.1.27)] and mitochondrial enzymes [pyruvate dehydrogenase (PDH; EC 1.2.4.1), alpha-ketoglutarate dehydrogenase (alpha-KGDH; EC 1.2.4.2)]. The CK activities were higher in fast-growing and CHF broilers as compared to slow-growing broilers (p<0.05). Cardiac LDH and alpha-KGDH activities were not changed (p>0.05), whereas PDH activity was highest (p<0.05) in broilers with CHF. Deterioration of heart function is correlated with lowered cardiac ATP, CrP, and l-carnitine levels (all p<0.05). Depletion of high energy phosphate substrates, ATP and CrP, is evident in fast-growing chickens and those that developed CHF. Increased activity of CK suggests that cardiac energy management in fast-growing broilers and those with CHF largely depends on contribution of this pathway to regeneration of ATP from CrP. In this scenario, inadequate level of CrP is a direct cause of ATP insufficiency, whereas low cardiac l-carnitine, because of its role in fatty acid transport, is most likely an important factor contributing to shortage of key substrate required for synthesis of cardiac ATP. The insufficiencies in cardiac energy substrate synthesis provide metabolic basis of myocardial dysfunction in chickens predisposed to heart failure.
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PMID:Biochemical factors limiting myocardial energy in a chicken genotype selected for rapid growth. 1798 9

Cofactor disorders of mitochondrial energy metabolism are a heterogeneous group of diseases with a wide variety of clinical symptoms, particular metabolic profiles and variable enzymatic defects. Mutations in NFU1, BOLA3, LIAS and IBA57 have been identified in patients with deficient lipoic acid-dependent enzymatic activities and defects in the assembly and activity of the mitochondrial respiratory chain complexes. Here, we report a patient with an early onset fatal lactic acidosis presenting a biochemical phenotype compatible with a combined defect of pyruvate dehydrogenase (PDHC) and 2-ketoglutarate dehydrogenase (2-KGDH) activities, which suggested a deficiency in lipoic acid metabolism. Immunostaining analysis showed that lipoylated E2-PDH and E2-KGDH were extremely reduced in this patient. However, the absence of glycine elevation, the normal activity of the glycine cleavage system and the normal lipoylation of the H protein suggested a defect of lipoic acid transfer to particular proteins rather than a general impairment of lipoic acid biosynthesis as the potential cause of the disease. By analogy with yeast metabolism, we postulated LIPT1 as the altered candidate gene causing the disease. Sequence analysis of the human LIPT1 identified two heterozygous missense mutations (c.212C>T and c.292C>G), segregating in different alleles. Functional complementation experiments in patient's fibroblasts demonstrated that these mutations are disease-causing and that LIPT1 protein is required for lipoylation and activation of 2-ketoacid dehydrogenases in humans. These findings expand the spectrum of genetic defects associated with lipoic acid metabolism and provide the first evidence of a lipoic acid transfer defect in humans.
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PMID:Mutations in the lipoyltransferase LIPT1 gene cause a fatal disease associated with a specific lipoylation defect of the 2-ketoacid dehydrogenase complexes. 2425 11