Insulin oxidation

Insulin Oxidation of tyrosine residues at pre-treated (+1.7V, 30s) microfabricated SPCEs Potentiometric stripping analysis (2 min accumulation at -0.2V) Stripping current of 3 pA 0-600 nM 20nM Wang et al. [76]... 

Disulfides. As shown in Figure 4, the and h-chains of insulin are connected by two disulfide bridges and there is an intrachain cycHc disulfide link on the -chain (see Insulin and other antidiabetic drugs). Vasopressin [9034-50-8] and oxytocin [50-56-6] also contain disulfide links (48). Oxidation of thiols to disulfides and reduction of the latter back to thiols are quite common and important in biological systems, eg, cysteine to cystine or reduced Hpoic acid to oxidized Hpoic acid. Many enzymes depend on free SH groups for activation—deactivation reactions. The oxidation—reduction of glutathione (Glu-Cys-Gly) depends on the sulfhydryl group from cysteine. 

Alloxan (1003) has been observed in the mucus associated with dysentery and it was the very first pyrimidine made synthetically when Brugnatelli oxidized uric acid in 1818. Alloxan has an interesting diabetogenic action which appears to be associated with removal of essential zinc from insulin by chelation. Such permanent diabetes may be induced in fish, dogs, cats, sheep, some birds, monkeys and other creatures, but not in man, owls or guinea-pigs certain pyrimidines related to alloxan show some such activity. 

Antidiabetic Drugs other than Insulin. Figure 3 The antihyperglycaemic effect of metformin involves enhanced insulin-mediated suppression of hepatic glucose production and muscle glucose uptake. Metformin also exerts non-insulin-dependent effects on these tissues, including reduced fatty acid oxidation and increased anaerobic glucose metabolism by the intestine. FA, fatty acid f, increase i decrease. 

For the preparation of nanoparticles based on two aqueous phases at room temperature one phase contains chitosan and poly(ethylene oxide) and the other contains sodium tripolyphosphate. The particle size (200-1000 nm) and zeta potential (between -i- 20 mV and -l- 60 mV) could be modulated by varying the ratio chitosan/PEO-PPO. These nanoparticles have great proteinloading capacity and provide continuous release of the entrapped protein (particularly insulin) for up to one week [100,101]. 

Figure 2. Mechanism of PDH. The three different subunits of the PDH complex in the mitochondrial matrix (E, pyruvate decarboxylase E2, dihydrolipoamide acyltrans-ferase Ej, dihydrolipoamide dehydrogenase) catalyze the oxidative decarboxylation of pyruvate to acetyl-CoA and CO2. E, decarboxylates pyruvate and transfers the acetyl-group to lipoamide. Lipoamide is linked to the group of a lysine residue to E2 to form a flexible chain which rotates between the active sites of E, E2, and E3. E2 then transfers the acetyl-group from lipoamide to CoASH leaving the lipoamide in the reduced form. This in turn is oxidized by E3, which is an NAD-dependent (low potential) flavoprotein, completing the catalytic cycle. PDH activity is controlled in two ways by product inhibition by NADH and acetyl-CoA formed from pyruvate (or by P-oxidation), and by inactivation by phosphorylation of Ej by a specific ATP-de-pendent protein kinase associated with the complex, or activation by dephosphorylation by a specific phosphoprotein phosphatase. The phosphatase is activated by increases in the concentration of Ca in the matrix. The combination of insulin with its cell surface receptor activates PDH by activating the phosphatase by an unknown mechanism.

The rate of mitochondrial oxidations and ATP synthesis is continually adjusted to the needs of the cell (see reviews by Brand and Murphy 1987 Brown, 1992). Physical activity and the nutritional and endocrine states determine which substrates are oxidized by skeletal muscle. Insulin increases the utilization of glucose by promoting its uptake by muscle and by decreasing the availability of free long-chain fatty acids, and of acetoacetate and 3-hydroxybutyrate formed by fatty acid oxidation in the liver, secondary to decreased lipolysis in adipose tissue. Product inhibition of pyruvate dehydrogenase by NADH and acetyl-CoA formed by fatty acid oxidation decreases glucose oxidation in muscle. 

Enzymes of glycogenes Glycogen synthase system is,glycoiy T sis, and py T ruvate oxidation Insulin Insulin Glucose 6-phosphate Glucagon (cAMP) phos-phorylase, glycogen... 

Insulin, a small protein of molecular mass 6000 daltons, is composed of two chains designated A and B. There are no reduced cysteine residues in insulin, but it contains three essential disulfide bonds two that crosslink the A and B chains, and one internal to the A chain to stabilize the overall tertiary stmcture. These disulfide bonds are cleaved in the presence of excess AuX4, leaving A and B chains that have cysteine residues that have become oxidized to sulfonic adds [119]. With smaller amounts of AuX4, a single disulfide bond will be attacked to form sulfinic acid [119]. The reaction is second order for AuCU while AuBr4 reacts too quickly for accurate monitoring. 

Taken together, these observations emphasize the critical importance of maintaining the antioxidant potential of the pancreatic beta cell in ordet to ensure both its survival and insulin secretory capacity during times of increased oxidative stress. 

The aquation of [IrCl6]2- to [Er( E120)C1S] and Ir(H20)2Cl4 has been found to activate the complex toward the oxidation of insulin in acidic solutions, with measured rate constant of 25,900 and 8,400 Lmol-1 s 1, respectively.50 The oxidation reaction proceeds via an outer-sphere mechanism. 

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