Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.01 seconds)

Metabolic acidosis is common in babies fed cows' milk-based formulae. Therefore the effects of adding alkaline salts (sodium and potassium citrate) to a demineralised whey formula were studied in vitro and in 26 low birthweight babies fed on the formula or formula plus citrate. The alkali altered the pH and titratable acidity to a value nearer human milk but it increased the buffering capacity to a value further away. This may effect the bacterial flora of the intestine. The babies fed on formula plus citrate did not make greater gains in weight, length, head circumference, skinfold thickness, or midarm muscle circumference, although they had a greater blood base excess. Some of these babies developed a mild metabolic alkalosis and 3 had hyponatraemia despite their increased sodium intakes. These babies also had lower levels of plasma transferrin but showed no differences in urea, albumin, cholesterol, and calcium levels. No baby fed on the demineralised whey formula without added citrate had a base deficit exceeding 5 mmol/l; late metabolic acidosis is less common in babies fed on this formula and the routine addition of alkali can have untoward metabolic effects.
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PMID:Milk pH, acid base status, and growth in babies. 3 63

Conflicting data have been reported on "sports anaemia" and anaemia during physical training. Most of these results are of studies at rest before or after training. The aim of this investigation was to further study the profiles of serum iron (Se Fe) and transferrin (Se Tr), in 14 physically trained men (28 +/- 6 years) during an exhaustive interval training session. The 45 min Square-Wave Endurance Exercise Test (SWEET) was performed on a cycle ergometer. To the SWEET base, established as a % of individual VO2max, a peak of 1 min at VO2max was added every 5 minutes. Arterial blood samples were taken at rest, during the SWEET at the 14th, 15th, 29th, 30th, 44th and 45th minutes, just before and after the peaks, and at the 15th min of recovery. Lactate, acidity [H+], PaCO2, PaO2, Haematocrit (Hct), Haemoglobin (Hb), Se Fe and Se Tr were measured. After the SWEET, weight loss was 0.89 +/- 0.15 kg. Lactate and serum iron rose progressively at the base levels and at the peaks, while PaCO2 and bicarbonate fell progressively. Hct, [Hb], serum transferrin and [H+] increased significantly at the 14th min of SWEET and thereafter no change was observed. At the 45th min with respect to the value at rest, Se Fe increased as much as +32%, Se Tr +13% and [Hb] +8%. Haemoconcentration could explain the changes in Se Tr but not the total significant increase in Se, Fe, which moreover is not explained by acidosis [H+].(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum iron and transferrin during an exhaustive session of interval training. 334 80

Gastric juice and bile fractions A, B, C of 143 patients, vaginal secretion and cervical mucus of further 257 patients, and the sera of all patients, were studied for IgG, IgA, IgM, complement C3, albumin and transferrin, together with acidity tests and microbiological study. The data thus obtained, nearly 10 000 in number, were subjected to automated (factor) analysis. This revealed certain concealed relationships which has been superimposed by the manifestations: the specific defense of the mucous membranes resulting from the activity of the secretory immune system takes effect only under special conditions. The local secretory immune factors, together with the effects connected with acidity and proteolytic activity, are deployed only in the stomach and duodenum at the first level of mucous membrane defense. For the defense of the genital mucous membranes--in the period of sexual activity and reproduction--the transudative factors of the serum resulting from hormonal activity are responsible, and only if these factors are affected does the specific defense mechanism of the mucous membranes take action.
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PMID:Demonstration of the efficiency of specific mucous membrane defense by factor analysis. 409 38

When injected at tracer levels into the blood, radiogallium as 67Ga-citrate binds to, and it transported to the site of the tumor by, transferrin. The process by which transferrin-bound Ga is converted to tumor-bound Ga is not fully understood, but may involve the differential physiology of neoplasms compared with normal tissues. Based on the slight acidity known to be exhibited by the extracellular fluid of many animal and human tumors, we have studied the effect of pH on stability and dissociation of the Ga-transferrin complex and on the uptake of Ga by tumor cells in vitro and animal tumors in vivo. When plasma from rabbits injection 67Ga-citrate was dialyzed at pH 6.5-7.5, dissociation of Ga from transferrin showed an inverse pH-dependence. A similar inverse dependence on pH was observed for the uptake of Ga by L1210 leukemia cells and Ehrlich ascites cells incubated with Ga-transferrin complex. Tumor uptake of Ga in rats bearing Walker-256 carcinosarcoma or Murphystum lymphosarcoma whose tumor pH had been further lowered by administration of glucose showed a statistically significant increase over control rats receiving no glucose. These results demonstrate that the stability of the Ga-transferrin complex is pH-dependent and suggest that dissociation of this complex due to decreased pH at the tumor site may be one factor involved in tumor localization and binding of Ga.
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PMID:Effect of pH on tumor cell uptake of radiogallium in vitro and in vivo. 689 27

We attached human transferrin to Pseudomonas exotoxin A (PE) to specifically localize this toxin to the endosomal compartment and study its translocation from purified endosomes using a cell-free assay. Transferrin was linked to PE via a disulfide bond. Chemical derivatization inactivated the PE cell-binding domain, and transferrin-PE was found to be endocytosed via the transferrin receptor only. Transferrin was also conjugated to a truncated PE with no receptor-binding domain (PE46). After labeling mouse lymphocytes with radiolabeled transferrin-PE or transferrin-PE46 and endosome isolation, selective translocation of the full-sized toxin portion of the conjugate was observed in a cell-free system. This translocation was strictly dependent upon ATP hydrolysis and was not affected when the acidity of the endosome lumen was neutralized using weak bases, protonophores, or bafilomycin A1. Nevertheless, when present during cell labeling, inhibitors of endosome acidification prevented PE from acquiring translocation competence. Similar inhibition was observed when endocytosis was performed in the presence of brefeldin A, a drug known to interfere with the delivery of endocytic tracers to acidic endosomes. Our data indicate that full-length PE can be transferred to the cytosol directly from endosomes during intoxication by PE conjugates and that, although exposure to acidic pH is a prerequisite for translocation, ATP hydrolysis directly provides the energy required for PE translocation.
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PMID:Translocation of full-length Pseudomonas exotoxin from endosomes is driven by ATP hydrolysis but requires prior exposure to acidic pH. 882 63

A wide range of metal ions of natural, therapeutic, diagnostic and toxic interest are transported by serum transferrin (80 kDa). It is therefore important to understand the factors that control the strength of metal binding. We show here that even though Sc3+ has only slightly larger ionic radius than Fe3+ (0.075 nm versus 0.065 nm), it binds to the C-lobe and N-lobe sites much more weakly: logK1* (bicarbonate-independent binding constant) 14.6 +/- 0.2, logK2* 13.3 +/- 0.3, respectively (10 mM Hepes, 5 mM bicarbonate, 310 K). Preferential binding to the C-lobe was established by 1H-NMR spectroscopy. We show that the strength of binding of divalent and trivalent metal ions to human serum transferrin correlates with metal ion acidity [and therefore with the strength of binding to hydroxide, K1(OH)]. The correlations are of predictive value for a range of other metal ions. The plot of logK1* (human serum transferrin) versus logK1(OH) has a negative intercept consistent with unfavorable entropy effects due to lobe closure of apotransferrin on binding of metal ions. This interpretation was tested by comparison with similar correlations of the strength of metal binding to the enzymes carbonic anhydrase and carboxypeptidase with that for the low-M(r) ligand imidazole. These plots have positive intercepts consistent with the preorganized (entatic) state of these metalloenzymes (favorable entropy effects on metal binding).
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PMID:Rationalization of the strength of metal binding to human serum transferrin. 897 57

The oxidation of low density lipoprotein (LDL) within atherosclerotic lesions may be involved in atherogenesis. LDL oxidation by cells in the presence of iron is faster at acidic pH. In addition, LDL oxidation by iron alone or iron cysteine in the absence of cells is much faster at acidic pH, even at mildly acidic pH (pH 6.5). The effect of pH on LDL oxidation by copper ions is more complex, in that acidity slows down the initial oxidation, as measured by conjugated dienes, hydroperoxides and thiobarbituric acid-reactive substances, but can increase the later stages of LDL oxidation as measured by increased macrophage uptake. Extensive LDL oxidation by cells in atherosclerotic lesions probably requires a source of iron or copper as catalysts for the oxidation. Iron in plasma is carried by the protein transferrin. Lowering the pH releases some of the iron from transferrin so that it can catalyse LDL oxidation. Copper is carried in plasma on caeruloplasmin and becomes more effective in catalysing LDL oxidation when the caeruloplasmin is preincubated at acidic pH, or even at pH 7.0. These effects can be seen with concentrations of caeruloplasmin and transferrin below those present in plasma. By analogy to other inflammatory and ischaemic sites, atherosclerotic lesions may well have an acidic extracellular pH, particularly within clusters of macrophages where the oxidative stress may also be high. This localised acidic pH may help to explain why atherosclerotic lesions are one of the few sites in the body where extensive LDL oxidation occurs.
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PMID:Does an acidic pH explain why low density lipoprotein is oxidised in atherosclerotic lesions? 910 56

Difference infrared spectra are reported for human serum transferrin in D2O as a function of iron binding or increased acidity. Spectral features detected as iron is bound at high pH include difference bands that are indicative of reduced solvent exposure and binding site ligation. More extensive spectral alterations, some of which indicate titration of carboxylic acid groups, are induced in the apo protein by lowering the pH in a manner consistent with that entailed in endocytosis.
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PMID:Alteration of infrared spectrum of serum transferrin by iron binding and lowered pH. 1060 84

The binding of titanium(IV) to human serum transferrin in 50 mM Tris with 20 mM bicarbonate and 10 mM citrate at pH 7.4 was studied by UV/vis kinetics and by isothermal titration calorimetry. Ti(IV) citrate, [Ti(C6H4O7)3]8-, employed in this study was previously characterized and delivers the metal to transferrin rapidly, allowing the quantification of the intrinsic binding constants for Ti(IV) to the C- and N-sites of transferrin. The results after correcting for blood plasma conditions (pH 7.4, [HCO3-] = 27 mM) reveal that Ti(IV) binds with greater affinity (log K = 26.8 and 25.7) than Fe(III) (log K = 22.5 and 21.4) to transferrin, a finding not previously observed for other examined metal ions. The strength of metal binding to transferrin correlates with the Lewis acidity of the metal. Ti(IV) is more Lewis acidic than Fe(III) and is nearly the same size. The study also reveals that Ti(IV) binds more tightly to one site than the other, and this difference is due to both entropic and enthalpic contributions. The study has implications for the role of transferrin in the anticancer activity of Ti(IV) drugs and the serum binding of Ti(IV) ions released from implants or imaging reagents.
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PMID:Ti(IV) binds to human serum transferrin more tightly than does Fe(III). 1608 31

Cell-penetrating peptides (CPPs) can enter many types of cells and have become useful tools for introducing a variety of cargo such as exogenous peptides, proteins, and nucleic acids into cultured cells in vitro. Tat CPPs derived from the HIV-1 Tat protein are the most widely used among the arginine-rich CPPs. Even though CPPs hold considerable promise for drug delivery, poor biological stability and high in vivo clearance may limit their effectiveness for delivering cargo. Therefore, we utilize a retro-inverso form of a Tat peptide, R.I.-CKTat9, which is proteolytically stable. In the current study, the cellular entry mechanism of this arginine-rich CPP is investigated. Fluorescently labeled R.I.-CKTat9 entered HeLa cells in a concentration- and energy-dependent manner demonstrating both diffuse and punctate (vesicular) appearance inside the cells. The labeled R.I.-CKTat9 colocalized with labeled transferrin in the punctate structure, suggesting that the peptide enters HeLa cells by clathrin-dependent endocytosis. Incubation of cells with an isotonic/high K(+) buffer (KPBS) or an NH(4)Cl solution abolished the diffuse but not the punctate fluorescence, suggesting that membrane potential plays a critical role. This result also suggests that the flux originates from the endosome, not the extracellular space, and relies on the acidity of the endosome. Impairment of clathrin-mediated endocytosis by RNAi with clathrin heavy chain function and endocytosis inhibitors greatly reduced or completely abolished both diffuse and punctate fluorescence, further supporting a single route of endocytosis and subsequent endosomal escape. Since cells in the mitotic (M) phase shut down endocytosis but maintain plasma membrane potential, this property was used to further confirm the endocytic mechanism. Direct measurement of plasma membrane potential confirmed its persistence in M phase arrested HeLa cells. Consistent with our working hypothesis, these cells did not show any vesicular nor diffuse fluorescence of labeled R.I.-CKTat9, providing compelling evidence for the sequential steps of endocytosis and endosomal escape. Binding of labeled R.I.-CKTat9 to the surface of HeLa cells at 0 degrees C was reduced under the mildly acidic conditions of early endosomes, suggesting an acidity-dependent endosomal escape mechanism. Overall, these results indicate that both endocytosis and membrane potential are required for R.I.-CKTat9 entry into HeLa cells and suggest that translocation occurs at the endosomal membrane.
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PMID:Endocytosis and membrane potential are required for HeLa cell uptake of R.I.-CKTat9, a retro-inverso Tat cell penetrating peptide. 1927 21


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