Protein reduction

Although estrone and estradiol (26) have both been isolated from human urine, it has recently been shown that it is the latter that is the active compound that binds to the so-called estrogen receptor protein. Reduction of estrone with any of a large number of reducing agents (for example, any of the complex metal hydrides) leads cleanly to estradiol. This high degree of stereoselectivity to afford the product of attack at the alpha side of the molecule is characteristic of many reactions of steroids. 

The presence of two sulfhydryl groups in DTT and DTE, however, allows the formation of a favored cyclic disulfide during the course of target protein reduction (Figure 1.75). This drives the equilibrium toward the reduction of target disulfides. Therefore, complete reduction is possible with much lower concentrations of DTT or DTE than when using monothiol systems. 

Researchers studying the stepwise kinetics of nitrogenase electron transfer using stopped-flow kinetic techniques have presented other scenarios. One hypothesis presents kinetic evidence that dissociation of Fe-protein from MoFe-protein is not necessary for re-reduction of Fe-protein by flavodoxins.13 These authors state that the possibility of ADP-ATP exchange while Fe-protein and MoFe-protein are complexed with each other cannot be excluded and that dissociation of the complex during catalysis may not be obligatory when flavodoxin is the Fe-protein reductant. This leads to the hypothesis that MgATP binds to the preformed Fe-protein/... 

Local charge compensation of the formally charged Fe(III) heme, as discussed more fully in a later section, demonstrates a significant modulation (s 210 mV) of the heme reduction potential in a designed heme protein. This scaffold-dependent effect has been shown to be additive to the heme-dependent effect of porphyrin peripheral architecture to demonstrate the modulation of a designed heme protein reduction potential by 450 mV using a single maquette scaffold. 

Bearden and Moss (12) and Moss et al. (152) presented the Mossbauer spectra of spinach ferredoxin in its oxidized and reduced states. These spectra showed the two iron atoms in the oxidized protein in identical electronic environments. Upon protein reduction, one of the iron atoms exhibited a spectrum characteristic of a high-spin ferrous ion. The... 

In the clinic, PK/PD relationships with the direct pharmacological effect, reduction of target mRNA and protein as the response measure, have been demonstrated in two studies with 2 -MOE partially modified ASOs [42, 50]. In a Phase Ila study in patients with rheumatoid arthritis, ISIS 104838 was targeted at the mRNA of TNF-a (a cytokine which is important in immune response and inflammation). The results showed that TNF-a mRNA and protein reduction in synovial tissue biopsies correlated positively with concentrations of ISIS 104838 in the synovial tissues [50]. Another investigation of PK/PD relationships was conducted in a Phase II doseranging study in prostate cancer patients treated with OGX-Oll, a 2 -MOE partially... 

Fining also may be done to juice prior to fermentation. Protein fining agents may be used to reduce phenolics in press juice, or bentonite used for protein reduction or reduction of potential for hydrogen sulfide (H2S) production (18). 

Snell, AJM. The effects of chronic disease of the hver on the composition and physicochemical properties of blood changes in the serum proteins reduction in the oxygen satmation of the arterial blood. Ann. Intern. Med. 1935 9 690-711... 

In neonatal manifestation of OTC deficiency, lethargy, vomiting, refusal to take food, hyperventilation and hypothermia develop quickly. Death ensues in coma within a few days. Manifestation in infants or adolescents is based upon the residual activity of the defective enzyme. This course is also characterized by vomiting and lethargy. The clinical picture is aggravated by a protein-rich diet, whereas protein reduction improves the clinical situation. Without treatment, death occurs in a hepatic coma. 

Force-Clamp Spectroscopy of Single Proteins Reduction events 13.5 nm... 

A complex procedure for determining the content of asparagine and glutamine separately in proteins has been described (see Chibnall et al. 1958). This procedure makes use of esterification of the protein, reduction of the resulting esters of aspartic acid and glutamic acid with lithium borohydride and hydrolysis of asparagine and glutamine to the acids in which form they are analyzed. Despite the side reactions for which corrections must be made, this method, in conjunction with total enzymic hydrolysis, may be useful to those who must quantitatively estimate these 4 amino acids. 

Treatment is largely empirical, based on observations that intestinal bacteria and protein loads in the intestinal tract are important in the symptoms of hepatic encephalopathy. Lactulose has long been recognized to reduce the symptoms in chronic hepatic encephalopathy. Antibiotic treatment with a nonabsorbable antibiotic such as neomycin reduces the number of bacteria and is especially helpful in patients with GI bleeding. Protein reduction in the diet also improves encephalopathy reducing dietary protein to the less than 40g/day often needed to improve symptoms may compromise nutrition. Patients with acute encephalopathy require... 

Lgl binds to myosin II, which functions in cytokinesis (see Figure 19-20). Lgl Itself is uniformly localized around the cortex. Lgl is phosphorylated by the apical complex and may be inactivated on the apical side to allow basal Miranda accumulation. Two yeast proteins related to Lgl also bind to myosin II they have been implicated in exocytosis and secretion, specifically in the docking of post-Golgi vesicles with the plasma membrane (Chapter 17). Mutations in the two yeast proteins suppress mutations in the myosin II gene. This observation is interpreted to mean that the function of myosin II in spindle orientation is opposite to that of the Lgl-like proteins reduction of one protein s function is ameliorated by reduction of the other, restoring a semblance of the normal balance. In this case, therefore, myosin and Lgl probably act in opposite directions myosin II moving Miranda or other materials to control spindle orientation and Lgl restraining It. 

Losses in nutritional value would be an undesirable effect of chemical modification and would usually be avoided. However, for products incorporated into mixtures of different proteins, reductions in nutritional value of certain amino acids might be inconsequential because sufficient amounts of the destroyed amino acids could be supplied by the other... 

Reduction and Carboxymethylation of Proteins. Reduction of disulfide bridges with mercaptoethanol in 8M urea and reaction with iodo-acetate to introduce the carboxymethyl (CM) group onto the protein sulfhydryl groups have been described earlier (39). 

Effects on hepatic protein synthesis are caused by many hepatotoxins, but the changes may take some time to become apparent given the half-lives of the involved proteins. Reductions of plasma albumin and acid glycoprotein may affect the binding and exposures to xenobiotics and plasma bilirubin. Other effects on proteins may also be due to reduced food intake due to toxicity. The production of many plasma proteins, including those involved in complement and coagulation cascades, can be affected by reductions of hepatic protein synthesis. 

Clapp, W.L. A status report on protein reduction studies 767. 

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