Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The specificity and mode of action of an acid proteinase (EC 3.4.23.6) from Aspergillus saitoi were investigated with oxidized B-chain of insulin, angiotensin II and bradykinin. Further purification of acid proteinase was performed with N,O-dibenzyloxycarbonyl-tyrosine hexamethylene-diamino-Sepharose 4B affinity chromatography and isoelectric focusing. The purified enzyme was free of any other proteolytic activity demonstrated in Asp. saitoi. Acid proteinase from Asp. saitoi hydrolyzed primarily two peptide bonds in the oxidized B-chain of insulin, the Leu(15)-Tyr(16) bond and the Phe(24)-Phe(25) bond. Additional cleavages of the bonds His(10)-Leu(11), Ala(14)-Leu(15) and Tyr(16)-Leu(17) were also noted. Primary splitting sites at Leu(15)-Tyr(16) and Phe(24-)-Phe(25) with acid proteinase from Asp. saitoi were identical with those reported in the work of cathepsin D (EC 3.4.23.5) from human erythrocyte. Hydrolysis of angiotensin II was observed at the Tyr(4)-Ile(5) bond. In conclusion, peptide bonds which have a hydrophobic amino acid such as phenylalanine, tyrosine, leucine and isoleucine in the P'1 position (as defined by Berger and Schechter, [29]) are preferentially cleaved by the trypsinogenactivating acid proteinase from Asp. saitoi.
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PMID:Purification of an acid proteinase from Aspergillus saitoi and determination of peptide bond specificity. 2 99

A new protease, detected in an extract of Fasciola hepatica, was isolated and partly purified. The pH optimum for the cleavage of denaturated haemoglobin by the enzyme is pH 3.0. This proteolytic activity is inhibited by diazoacetylnorleucine methyl ester, pepstatin, the pepsin inhibitor from Ascaris suum, and phenylalanine. The cathepsin D inhibitor from potatoes, EDTA, mercaptoethanol and the inorganic salts tested have no inhibitory effect. The cleavage of the B-chain of oxidized insulin by enzyme was studied and compared with the digestion of the same substrate by chicken and pig pepsin. The protease from Fasciola hepatica belongs to the carboxyl group of proteases and probably plays an important role in helminth nutrition.
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PMID:Isolation and some properties of an acid protease from Fasciola hepatica. 4 1

Leucine, but not isoleucine or valine, inhibited protein degradation and accelerated protein synthesis in hearts perfused with buffer that contained glucose (15 mM) and normal plasma levels of other amino acids, except for the branched chain compounds. Products of leucine, isoleucine, and valine metabolism also inhibited protein degradation and stimulated protein synthesis. These compounds included the transamination and decarboxylation products, as well as acetate, acetoacetate, and propionate. In some, but not all instances, inhibition of degradation and acceleration of synthesis were accompanied by an increase in intracellular leucine. When insulin was added to the perfusate, the rate of degradation was reduced by 40%, but addition of leucine was ineffective in the presence of the hormone. Insulin, leucine (2 mM) and a mixture of branched chain amino acids at normal plasma levels increased latency of cathepsin D in hearts that were perfused with buffer containing glucose. A combination of leucine and insulin increased latency more than either substance alone. These studies indicate that leucine as well as a variety of substrates that are oxidized in the citric acid cycle are involved in regulation of protein turnover in heart muscle.
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PMID:Effect of leucine and metabolites of branched chain amino acids on protein turnover in heart. 46 30

In fetal mouse hearts in organ culture the rate of protein synthesis was substantially reduced and the rate of protein degradation slightly increased by hydrocortisone in the absence of insulin, but in the presence of insulin the steroid caused a small increase in protein synthesis and a significant reduction in protein degradation. Hydrocortisone promoted the net uptake (or reduced the net release) of branched-chain amino acids independent of insulin and independent of simultaneous changes in protein balance. The specific activities of the lysosomal enzymes cathepsin D and glucosaminidase were reduced by hydrocortisone in all media, whereas the specific activity of creatine kinase increased when the medium contained insulin but decreased in the absence of insulin. It is concluded that hydrocortisone regulates cardiac protein balance via alterations both in synthesis and in degradation. Some of the hormone's myocardial effects are influenced by insulin so that hydrocortisone is anabolic in its presence but catabolic in its absence.
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PMID:Regulation of cardiac protein balance by hydrocortisone: interaction with insulin. 62 46

The effect of insulin on the concentration of different glycosaminoglycan (CG) fractions was different in different segments of aorta. Chondroitin sulphate A and heparin were increased in the aortic arch, thoracic and abdominal aorta, while chondroitin sulphate B and C were increased only in the aortic arch and abdominal aorta. Heparin sulphate and hyalutonic acid were increased only in the abdominal aorta. In the liver, significant increases occurred in all GG fractions. All enzymes studied which are involved in the biosynthesis of GG precursors, i.e. glucosaminphosphate isomerase, UDP glucose dehydrogenase and glucose-1-phosphate uridylyltransferase, were increased in the animals of the insulin group, while all enzymes involved in the degradation of GG, i.e. hyalurono glucosidase, beta-glucosaminidase, arylsulphatase, and cathepsin D, were decreased. Concentration of hepatic PAPS, activity of the sulphate-activiting system and sulphotransferase increased on administration of insulin.
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PMID:Insulin and metabolism of glycosaminoglycans in rabbits. 71 66

Net changes in the concentrations of 18 amino acids in perfusate and skeletal muscle were followed during perfusion of hemicorpus preparations from fed rat. Perfusate levels of 16 amino acids showed little change from their initial concentrations during the 1st h, but increased dramatically during the 2nd and 3rd h. Aspartate and glutamate levels decreased continuously throughout the perfusion. Release of alanine and glutamine accounted for approximately 50% of the total change in perfusate amino acids. The increase in perfusate amino acids was derived from net breakdown of muscle proteins and not from leakage from the intracellular pool as evidenced by elevated concentrations of intracellular amino acids in perfused muscle. Addition of insulin to the perfusate did not change the pattern of amino acid release during the 1st h of perfusion. However, during the 2nd and 3rd h the hormone completely prevented the net release of most amino acids and maintained intracellular concentrations of most amino acids at levels found in upperfused tissue. Effects of time of perfusion and insulin on amino acid release were accounted for by changes in the rate of protein turnover. Protein synthesis in gastrocemius and psoas muscles in control perfusions decreased after 1 h to approximately 50% of the initial rate. This decrease was accompanied by a 2-fold increase in the level of ribosomal subunits, indicating development of a block in peptide chain initiation. Addition of insulin maintained the initial rate of synthesis and the in vivo level of ribosomal subunits, demonstrating that the hormone prevented the block in peptide chain initiation from forming. Addition of insulin after 2 h reversed the perfusion-induced block in initiation. Synthesis of the specific muscle protein myosin was increased 45% over the control rate in the presence of insulin. Insulin also produced a 50% decrease in the rate of protein degradation during the 2nd and 3rd h of perfusion. A similar effect was noted when protein synthesis was inhibited by addition of cycloheximide. Higher concentrations of insulin were required to maximally inhibit protein degradation than to increase protein synthesis. Involvement of lysosomal proteases in the effect of insulin on protein degradation was evaluated by measuring cathepsin D activity in psoas muscle homogenates. "Free" enzyme activity increased as a result of perfusion while addition of insulin maintained this activity at the unperfused level. Neither perfusion nor insulin had any effect on total cathepsin D activity. Alterations in protein degradation and lysosomal enzyme activity were not due to changes in levels of adenine nucleotides, GTP, or creatine phosphate.
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PMID:Regulation by insulin of amino acid release and protein turnover in the perfused rat hemicorpus. 83 25

Prolonged starvation is known to induce significant alterations in several cardiac lysosomal enzymes, particularly the acid proteinase cathepsin D. To determine what specific factors might mediate these changes, fetal mouse hearts in organ culture were maintained in media designed to simulate selected hormonal or nutritional substrate changes that accompany starvation. Reduced concentrations of glucose caused an increase in the activity of beta-acetylglucosaminidase but had no effect on cathepsin D or acid phosphatase activites (i.e., effects opposite from those of starvation). Also, high concentrations of free fatty acid, acetoacetate, and beta-OH-butyrate induced an increase in cathepsin D (+18%) and a simultaneous decrease in glucosaminidase (-19%), with little change in acid phosphatase. Furthermore, glucagon had no effect on any of the enzymes, whereas growth hormone caused a small (6%) increase in cathepsin D activity. In addition, insulin deprivation caused significant increases (7-25%) in the activities of all three enzymes. Insulin deprivation and excess ketones, but not the other interventions, increased the proportion of enzyme activity which was nonsedimentable. These results suggest the possibility that lysosomal alterations during starvation may be related in part to prolonged insulin deficiency and exposure to high concentrations of ketones and free fatty acids.
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PMID:Hormonal and nutritional substrate control of cardiac lysosomal enzyme activities. 95 75

The action of uterine cathepsin D on the insulin A-chain (S-sulfo) and porcine glucagon was compared with the action of bovine dental pulp cathepsin on the same substrates. Differences observed with respect to molecular and catalytic properties suggest that different gene products (coding for the same function) are used during cell differentiation.
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PMID:Specificity and some physical properties of cathepsin D from bovine uterus and dental pulp. 105 48

The effect of insulin on turnover of protein was investigated in isolated perfused rat hearts. The hormone lowered intracellular levels of nine amino acids and reduced or abolished net release of 10 amino acids and ammonia. The extent of the insulin effect on protein degradation was investigated by estimating the rate of dilution of the specific radioactivity of the free phenylalanine pool. Insulin concentrations greater than 200 microunits per ml reduced protein degradation and net phenlylalanine release. Protein degradation was estimated more directly by inhibiting reincorporation of nonradioactive phenylalanine from protein with cycloheximide. Addition of the inhibitor increased the estimated rates about 50%, but the magnitude of the hormone effect was similar. The latency of lysosomal enzymes in control and insulin-treated hearts was assessed by measuring activities of beta-acetylglucosaminidase and cathepsin D in heart homogenates in the presence and absence of Triton X-100. Perfusion with insulin-free buffer increased the activities assayable without detergent, but did not change total activities of these enzymes. Insulin decreased activities assayable without detergent and increased activities sedimenting in the 10-5 times g pellet. These studies showed that insulin restricted the rate of protein degradation in the isolated perfused rat heart. Concomitantly, the latency of lysosomal enzymes was increased when the hormone was provided.
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PMID:Effect of insulin on protein turnover in heart muscle. 111 24

The present studies were aimed to evaluate the possibility to use a system for estimation in vitro of the biosynthesis and degradation rates of human skeletal muscle protein. A previously characterized human skeletal muscle preparation was used. Amino acids and insulin stimulated significantly the incorporation rate of leucine into proteins. The effect of amino acids was more pronounced than that of insulin. The stimulatory effect of insulin could be decreased by amino acids. Insulin did not influence the tissue uptake or the oxidation rate of leucine. The release of [14C]leucine deriving from degradation of prelabelled skeletal muscle fibre proteins was linear for at least 2.5 h of incubation and optimal with leucine at concentrations beyond 12.5 mmol/1 or in the presence of puromycin in the incubation medium. The rate of the release of radioactivity was significantly inhibited by amino acids and at borderline significance by insulin but not by puromycin. The specific radioactivity in prelabelled proteins decreased significantly in the presence of puromycin suggesting that leucine derived from protein degradation was reutilized in vitro. This reutilization was found to be 9 +/- 1% of leucine released from degradation of proteins in 30 subjects. A statistically significant positive correlation between the cathepsin D activity in human skeletal muscle tissue and the degradative rate of prelabelled muscle proteins in vitro was observed. The results indicate that biosynthesis and degradation of skeletal muscle proteins in this system in vitro were subjected to control mechanisms. It is suggested that the release of radioactivity from prelabelled muscle fibre proteins during incubation probably only reflects the degradation of some rapidly-turning-over proteins.
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PMID:Determination in vitro of the rate of protein synthesis and degradation in human-skeletal-muscle tissue. 120 38


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