scispace - formally typeset
Search or ask a question

Showing papers on "Serum albumin published in 2022"


Journal ArticleDOI
TL;DR: The authors in this paper performed a secondary analysis of the EFFORT trial, a Swiss-wide multicentre, randomised controlled trial comparing individualised nutritional support with usual care nutrition in medical inpatients from April 1, 2014, to February 1, 2018.

17 citations


Journal ArticleDOI
TL;DR: In this paper, the interaction of drug Bisacodyl (BSL) with carrier proteins viz; Bovine Serum Albumin (BSA), HSA and BHb via static quenching mechanism has been studied.

14 citations


Journal ArticleDOI
TL;DR: This review would like to scrutinize what is currently known and share information to develop next-generation albumin carriers that focus on interactions with albumin receptors.
Abstract: Albumin, the most abundant protein in human serum, is applied to various diseases as a drug delivery carrier because of its superior blood retention, high biocompatibility, and a wide variety of drug binding abilities. Albumin is known to distribute widely in the blood and various interstitial fluids and organs. Different albumin receptors skillfully regulate the distribution characteristics of albumin in the body. Albumin receptors are a group of diverse proteins, such as FcRn, gp60, gp18, megalin, cubilin, SPARC, and CD36. Their tissue distributions in vivo are unique, with different albumin's recognition sites. Therefore, the distribution of albumin in vivo is ingeniously controlled by these multiple albumin receptors. Reevaluation of these albumin receptors opens up new possibilities for applying albumin as a drug delivery carrier. If the tissue distributions of albumin receptors were known and the albumin recognition site of the receptor was identified, organ-specific active targeting would be possible. In this review, we would like to scrutinize what is currently known and share information to develop next-generation albumin carriers that focus on interactions with albumin receptors.

12 citations


Journal ArticleDOI
TL;DR: In this paper , an improved binary mutant quantum grey wolf optimizer (MQGWO) combined with Fuzzy K-Nearest Neighbor (FKNN) was used for detecting serum albumin level trends in hemodialysis patients.

11 citations


Journal ArticleDOI
TL;DR: In this article, an improved binary mutant quantum grey wolf optimizer (MQGWO) combined with Fuzzy K-Nearest Neighbor (FKNN) was used for detecting serum albumin level trends in hemodialysis patients.

11 citations


Journal ArticleDOI
TL;DR: The control of obesity is the key to prevent the onset of non-alcoholic fatty liver disease, diabetes and metabolic dysfunctions.
Abstract: Obesity is hallmarked by endoplasmic reticulum (ER) stress, chronic inflammation and metabolic dysfunctions. The control of obesity is the key to prevent the onset of non-alcoholic fatty liver disease, diabetes,...

10 citations


Journal ArticleDOI
TL;DR: In this article , the interaction of drug Bisacodyl (BSL) with carrier proteins viz; Bovine Serum Albumin (BSA), HSA and BHb via static quenching mechanism has been studied.

10 citations


Journal ArticleDOI
TL;DR: In this article, the authors summarize how albumin with unique properties affects chemotherapeutic drugs efficacy from the aspects of drug outcome in blood, toxicity, tumor accumulation and direct or indirect interactions with fatty acids, plus application of albuminbased carriers for anti-tumor drug delivery.

9 citations


Journal ArticleDOI
TL;DR: Riboflavin is a redox-active vitamin that plays a pivotal role in human energy metabolism and has beneficial health effects by increasing extracellular antioxidant capacity, thereby alleviating oxidative stress as discussed by the authors .

9 citations


Journal ArticleDOI
TL;DR: In this paper , the authors summarize how albumin with unique properties affects chemotherapeutic drugs efficacy from the aspects of drug outcome in blood, toxicity, tumor accumulation and direct or indirect interactions with fatty acids, plus application of albuminbased carriers for anti-tumor drug delivery.
Abstract: Albumin, as the most abundant plasma protein, plays an integral role in the transport of a variety of exogenous and endogenous ligands in the bloodstream and extravascular spaces. For exogenous drugs, especially chemotherapeutic drugs, binding to and being delivered by albumin can significantly affect their efficacy. Meanwhile, albumin can also bind to many endogenous ligands, such as fatty acids, with important physiological significance that can affect tumor proliferation and metabolism. In this review, we summarize how albumin with unique properties affects chemotherapeutic drugs efficacy from the aspects of drug outcome in blood, toxicity, tumor accumulation and direct or indirect interactions with fatty acids, plus application of albumin-based carriers for anti-tumor drug delivery.

9 citations


Journal ArticleDOI
TL;DR: In this paper , the authors attempted to determine which malnutrition diagnostic variables can be used as predictors of postoperative complications in patients with head and neck squamous cell carcinoma, and found that serum albumin measured on the first postoperative day was the only variable that significantly differed between groups.

Journal ArticleDOI
TL;DR: In the present study, human serum albumin as the major transporter of fatty acids was modified with glyoxal under physiological conditions, andryptic peptide mapping enabled us to relate these findings to molecular changes at specific binding sites.
Abstract: Glycation significantly alters the physicochemical and biofunctional properties of proteins in foods and in vivo. In the present study, human serum albumin (HSA) as the major transporter of fatty acids was modified with glyoxal under physiological conditions. Reversibly albumin-bound glyoxal was removed, and advanced glycation end products were quantitated by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The total modification of protein-bound lysine and arginine residues reached up to 4.2 and 9.6%, respectively. The impact of these modifications on the transport capacity of long-chain fatty acids was characterized by spin-labeled fatty acid probes via electron paramagnetic resonance spectroscopy. With increasing degree of glycation, the equivalence of the seven binding sites of native HSA with a dissociation constant of 0.74 ± 0.09 μM was set off with only the three high-affinity sites 2, 4, and 5 remaining (0.46 ± 0.07 μM). The other four sites were shifted to low affinities with significantly higher dissociation constants (1.32 ± 0.35 μM). Tryptic peptide mapping enabled us to relate these findings to molecular changes at specific binding sites. Modification hotspots identified were lysine 351, 286, 159 and arginine 144, 485, 117. Further investigation of plasma protein samples of uremic patients vs healthy controls gave first insights into the in vivo situation.

Journal ArticleDOI
Sadullayev Shohruh1
TL;DR: In this paper , the association of hypoalbuminemia with mortality in critically ill patients requiring continuous renal replacement therapy (CRRT) was assessed in a large cohort of patients.

Journal ArticleDOI
TL;DR: In this article , the interaction between diltiazem hydrochloride (DTZ) and bovine serum albumin (BSA) was probed by fluorescence, UV-vis absorption, Fourier transform infrared, circular dichroism spectroscopies and molecular docking analysis at pH = 7.4.

Journal ArticleDOI
TL;DR: The interaction of allicin with bovine serum albumin (BSA) and its effect on the structure of protein were investigated in this article , where the number of binding sites and binding constants were measured by fluorescent quenching method, and the results provided important insight into the study of prevailing role of protein in drug pharmacokinetics and pharmacodynamics.
Abstract: The interaction of allicin with bovine serum albumin (BSA) and the effect of allicin binding on the structure of protein were investigated. The BSA fluorescence displayed decreased fluorescence strength after binding with allicin, which quenched BSA fluorescence in a concentration-dependent manner. The number of binding sites and binding constants were measured by fluorescent quenching method. The result of reverse phase HPLC showed that the peak of BSA shifted to higher retention time, which indicated that allicin had bound to BSA. 88.4 % of total free thiol groups of BSA have bound to allicin at the allicin/BSA molar ratio of 0.1. Allicin could destabilize the secondary and tertiary structure of BSA. At the allicin/BSA ratio of 0.1, the BSA's circular dichroism spectrum showed that allicin caused a decrease of α-helix content and a significant increase of the β-sheet content (p < 0.05). Changes in surface hydrophobicity indicated that more hydrophobic groups were exposed due to the action of allicin. These results provide important insight into the study of prevailing role of protein in drug pharmacokinetics and pharmacodynamics.

Journal ArticleDOI
TL;DR: One hundred twenty-three recently reported novel O-phosphorylation, glycation, methylation, carbonylation, and acetylation of albumin are reviewed and potential impact of these PTMs on albumin functions is discussed.
Abstract: Post-translational modifications (PTMs) may affect functions of human serum albumin. Here we review reports of novel PTMs of human serum albumin. One hundred twenty-three recently reported novel O-phosphorylation, glycation, methylation, carbonylation, and acetylation of albumin are reviewed. Potential impact of these PTMs on albumin functions is discussed. Knowledge of these PTMs of albumin is of importance for use of albumin in medical applications, e.g., in transfusion, drug formulations and remedies.

Journal ArticleDOI
TL;DR: In this article , the authors found a strong negative correlation between decrease in serum albumin level and increase number of deaths from COVID-19 pneumonia in 76 patients who were admitted in ICU for more than four days and 38 patients expired.
Abstract: To establish correlation between serum albumin during early days of ICU admission and risk of death in COVID-19 pneumonia.In this retrospective study, we included 76 patients hospitalized in ICU, who stayed for at least four days with COVID-19 pneumonia, from May 1, 2020 to June 30, 2020 in Lahore Health Care Hospital and Al-Shafi Hospital. Patients were labelled as COVID-19 pneumonia on radiological basis as bilateral 'ground-glass opacity' in lower zones and RT-PCR positive result in nasopharyngeal swab. All patients were oxygen dependent, either on high flow oxygen via non rebreathing mask or invasive positive pressure ventilation support. Serum albumin levels were measured daily from first day to fourth day of ICU admission. The data was analyzed using SPSS version 26 and Microsoft excel 2016.Out of 76 patients of COVID-19 pneumonia admitted in ICU who stayed for more than four days, 38 patients expired. The mean age of all the patients was 58.9±12.56 years, 38(50%) of the patients were ≥60 years and 49 (62%) of them were male. On day four of ICU admission, mean serum albumin of discharged patients was 3.83±0.22 g/dl while mean serum albumin level of expired patients was 2.96±0.46 g/dl. Strong negative correlation (r = -767) was found between decrease in serum albumin level and increase number of deaths from COVID-19 pneumonia. Weak correlation was observed between increase in serum CRP and increase number of deaths in the same patients.Daily monitoring of serum albumin level of COVID-19 pneumonia patients can be used as a biological marker for monitoring of cytokine storm and risk of death in COVID-19 pneumonia.

Journal ArticleDOI
TL;DR: In this paper , the authors developed a ratiometric fluorescent probe with multiple advantages through a systematic structure variation of a benzocoumarin fluorophore and, further, a prototype of a smartphone-based point-of-care device.
Abstract: Human serum albumin exerts multifunctions, such as maintaining the oncotic pressure of plasma, carrying hydrophobic molecules, and acting as the most important antioxidant in the blood. Lower serum albumin levels are linked to several cardiovascular diseases, and dysfunction of albumin reabsorption in the kidney is linked to liver disease, renal disorder, and diabetes. Albumin is thus a powerful diagnostic and prognostic marker; however, its quantification in urine by readily affordable tools is challenging owing to its very low concentration. To address this issue, we developed a ratiometric fluorescent probe with multiple advantages through a systematic structure variation of a benzocoumarin fluorophore and, further, a prototype of a smartphone-based point-of-care device. We determined albumin levels in urine and observed that a smoking person has notably higher urine albumin than a nonsmoking person. The cheap device provides a promising tool for albumin-associated disease diagnosis in communities with limited resources.

Journal ArticleDOI
TL;DR: In this article , the binding of carbofuran at Site I of bovine serum albumin was confirmed by competitive molecular docking studies and the Stern-Volmer constant (Ksv) was found to be 2.02 × 104 dm3 mol−1 at 298 K.

Journal ArticleDOI
TL;DR: In this paper, carbofuran is examined for interaction with bovine serum albumin across several spectroscopic methods and may provide new insights into the mechanism of carb ofuran toxicity and its health consequences.

Journal ArticleDOI
TL;DR: In this paper , the drug-human serum albumin binding interaction was evaluated on a stationary phase immobilized with human serum albumins using a mixture of phosphate buffer (pH 7.0) and acetonitrile modifier as mobile phase.

Journal ArticleDOI
TL;DR: The present retrospective observational study examined nutritional status among patients receiving maintenance hemodialysis with different degree of hyperparathyroidism and found the role of extreme PTH level in protein-energy wasting emphasizing the importance of early management of hyper parathyroidistan.
Abstract: Severe hyperparathyroidism predicts poor outcomes in patients with kidney failure. Mechanisms underlying the relationship between high parathyroid hormone (PTH) and decreased survival other than bone loss are largely unexplored. Recent evidence suggests the role of excess PTH in adipose tissue browning resulting in protein-energy wasting. The present retrospective observational study examined nutritional status among patients receiving maintenance hemodialysis with different degree of hyperparathyroidism. Seven hundred forty-five patients were categorized into four groups according to PTH levels: group 0, < 200; group 1, 200–599; group 2, 600–1,499; and group 3, ≥1,500 pg/ml. Group 0 was excluded because of the relationship between low PTH with aging and malnutrition. Patients in groups 1 and 2 were matched to group 3 by propensity score yielding 410 patients in the final analysis. Nutritional parameters at baseline and the preceding 1 and 2 years were examined. At baseline, lower serum albumin, creatinine/body surface area (Cr/BSA), height in female and higher percentage of patients with serum albumin < 38 g/L were observed in group 3 compared to groups 1 and 2. Higher PTH level was independently associated with serum albumin < 38 g/L and Cr/BSA < 380 μmol/L/m2. The longitudinal decline in serum albumin and Cr/BSA and the increase in the frequency of patients with serum albumin < 38 g/L were observed among patients in group 3. Between group comparisons confirmed a significant decline in serum albumin and Cr/BSA in association with an increase in the proportion of patients with serum albumin < 38 g/L and Cr/BSA < 380 μmol/L/m2 in group 3 compared to groups 1 and 2. Weight loss was more significant and was of greater magnitude among patients in group 3 compared to groups 1 and 2. Normalized protein catabolic rate in 3 groups were comparable. There was no significant difference in any of the nutritional parameters between groups 1 and 2. In conclusion, patients receiving maintenance hemodialysis with severe hyperparathyroidism showed deterioration of nutritional status compared to patients with moderate hyperparathyroidism and patients with PTH level in the recommended range. These findings support the role of extreme PTH level in protein-energy wasting emphasizing the importance of early management of hyperparathyroidism.

Journal ArticleDOI
TL;DR: In this paper , the authors analyzed data that had been consecutively collected from January 2016 to December 2020 at the Third Affiliated Hospital and divided the patients into four groups based on their serum albumin levels (albumin ≥ 3.0 g/dL or < 3.
Abstract: Hypoalbuminemia at the initiation of continuous renal replacement therapy (CRRT) is a risk factor for poor patient outcomes. However, it is unknown whether the patterns of changes in serum albumin levels during CRRT can be used to predict patient outcomes.This retrospective study analyzed data that had been consecutively collected from January 2016 to December 2020 at the Third Affiliated Hospital. We included patients with acute kidney injury who received CRRT for ≥ 72 h. We divided the patients into four groups based on their serum albumin levels (albumin ≥ 3.0 g/dL or < 3.0 g/dL) at the initiation and termination of CRRT.The 793 patients in this study were categorized into the following albumin groups: persistently low, 299 patients (37.7%); increasing, 85 patients (10.4%); decreasing, 195 patients (24.6%); and persistently high, 214 patients (27.1%). In-hospital mortality rates were highest in the persistently low and decreasing groups, followed by the increasing and persistently high groups. The hazard ratio for in-hospital mortality was 0.481 (0.340-0.680) in the increasing group compared to the persistently low group; it was 1.911 (1.394-2.620) in the decreasing group compared to the persistently high group. The length of ICU stay was 3.55 days longer in the persistently low group than in the persistently high group.Serum albumin levels changed during CRRT, and monitoring of patterns of change in serum albumin levels is useful for predicting in-hospital mortality and the length of ICU stay.

Journal ArticleDOI
TL;DR: In this article , the authors evaluated perioperative albumin level independently and as part of the albumin-bilirubin (ALBI) grade, as a predictor of post-liver transplant hospital and intensive care unit (ICU) length of stay (LOS).
Abstract: Introduction Serum albumin’s association with liver transplant outcomes has been investigated with mixed findings. This study aimed to evaluate perioperative albumin level, independently and as part of the albumin–bilirubin (ALBI) grade, as a predictor of post-liver transplant hospital and intensive care unit (ICU) length of stay (LOS). Methods Adult liver-only transplant recipients at our institution from September 2011 to May 2019 were included in this retrospective study. Repeat transplants were excluded. Demographic, laboratory, and hospital course data were extracted from an institutional data warehouse. Negative binomial regression was used to assess the association of LOS with ALBI grade, age, BMI, ASA score, Elixhauser comorbidity index, MELD-Na, warm ischemia time, units of platelets and cryoprecipitate transfused, and preoperative serum albumin. Results Six hundred and sixty-three liver transplant recipients met inclusion criteria. The median preoperative serum albumin was 3.1 [2.6–3.6] g/dL. The median postoperative ICU and hospital LOS were 3.8 [2.4–6.8] and 12 [8–20] days, respectively. Preoperative serum albumin predicted hospital but not ICU LOS (ratio .9 [95% confidence interval (CI) .84–.99], P = .03, hospital LOS vs ratio .92 [95% CI 0.84–1.02], P = .10, ICU LOS). For patients with MELD-Na ≤ 20, ALBI grade-3 predicted longer hospital and ICU LOS (ratio 1.40 [95% CI 1.18–1.66], P < .001, hospital LOS vs ratio 1.62 [95% CI 1.32–1.99], P < .001, ICU LOS). These associations were not significant for patients with MELD-Na > 20. Conclusions Serum albumin predicted post-liver transplant hospital LOS. ALBI grade-3 predicted increased hospital and ICU LOS in low MELD-Na recipients.

Journal ArticleDOI
TL;DR: In this paper , an ionic-liquid-based aqueous biphasic system (IL-based ABS) was proposed for the extraction and separation of bovine serum albumin (BSA) from its original matrix.
Abstract: In this work, the extraction and separation of bovine serum albumin (BSA) from its original matrix, i.e., bovine serum, was performed using a novel ionic-liquid-based aqueous biphasic system (IL-based ABS). To this end, imidazolium-, phosphonium-, and ammonium-based ILs, combined with the anions’ acetate, arginate and derived from Good Buffers, were synthesized, characterized, and applied in the development of ABS with K2HPO4/KH2PO4 buffer aqueous solutions at pH 7. Initial studies with commercial BSA revealed a preferential migration of the protein to the IL-rich phase, with extraction efficiencies of 100% obtained in a single-step. BSA recovery yields ranging between 64.0% and 84.9% were achieved, with the system comprising the IL tetrabutylammonium acetate leading to the maximum recovery yield. With this IL, BSA was directly extracted and separated from bovine serum using the respective ABS. Different serum dilutions were further investigated to improve the separation performance. Under the best identified conditions, BSA can be extracted from bovine serum with a recovery yield of 85.6% and a purity of 61.2%. Moreover, it is shown that the BSA secondary structure is maintained in the extraction process, i.e., after being extracted to the IL-rich phase. Overall, the new ABS herein proposed may be used as an alternative platform for the purification of BSA from serum samples and can be applied to other added-value proteins.

Journal ArticleDOI
TL;DR: In this article , a prospective observational study on adult patients hospitalized for SARS-CoV-2 pneumonia (March-September 2020) was conducted, where the combined role of vitamin D and albumin serum levels as predictors of COVID-19 disease progression was assessed.
Abstract: We aimed to assess the combined role of vitamin D and albumin serum levels as predictors of COVID-19 disease progression.We conducted a prospective observational study on adult patients hospitalized for SARS-CoV-2 pneumonia (March-September 2020). Vitamin D and albumin serum levels were measured on admission. These variables were categorized in albumin < 3.5 or ≥ 3.5 g/dL and vitamin D < 30 ng/mL or ≥ 30 ng/mL. We excluded patients with known bone diseases, renal failure, hypercalcemia and/or treated with antiepileptic drugs and steroids, and patients who received previous vitamin D supplementation. A composite outcome including any ventilatory support, PaO2/FiO2 ratio, and 60-day mortality was defined.Sixty-nine patients were enrolled, of whom 50% received non-invasive (NIV) or invasive mechanical ventilation (IMV), 10% died, whereas 89% and 66% presented low albumin and low vitamin D serum levels, respectively. No correlation between vitamin D and albumin levels was found. In multivariable logistic regression analyses adjusted for sex and age-corrected comorbidities, patients having albumin < 3.5 g/dL and vitamin D < 30 ng/mL showed a significant increased risk for all study outcomes, namely NIV/IMV (OR 3.815; 95% CI 1.122-12.966; p = 0.032), NIV/IMV or death (OR 3.173; 95% CI 1.002-10.043; p = 0.049) and PaO2/FIO2 ≤ 100 (OR 3.410; 95% CI 1.138-10.219; p = 0.029).The measurement of both vitamin D and serum albumin levels on COVID-19 patients' admission, and their combined evaluation, provides a simple prognostic tool that could be employed to guide prompt clinical decisions.

Journal ArticleDOI
TL;DR: In this article , the authors performed intravital imaging on livers and kidneys of anesthetized mice to quantify the spatio-temporal tissue distribution of the mycotoxin ochratoxin A (OTA) based on its auto-fluorescence in albumin knockout and wild-type mice.
Abstract: Hypoalbuminemia (HA) is frequently observed in systemic inflammatory diseases and in liver disease. However, the influence of HA on the pharmacokinetics and toxicity of compounds with high plasma albumin binding remained insufficiently studied. The 'lack-of-delivery-concept' postulates that HA leads to less carrier mediated uptake of albumin bound substances into hepatocytes and to less glomerular filtration; in contrast, the 'concept-of-higher-free-fraction' argues that increased concentrations of non-albumin bound compounds facilitate hepatocellular uptake and enhance glomerular filtration. To address this question, we performed intravital imaging on livers and kidneys of anesthetized mice to quantify the spatio-temporal tissue distribution of the mycotoxin ochratoxin A (OTA) based on its auto-fluorescence in albumin knockout and wild-type mice. HA strongly enhanced the uptake of OTA from the sinusoidal blood into hepatocytes, followed by faster secretion into bile canaliculi. These toxicokinetic changes were associated with increased hepatotoxicity in heterozygous albumin knockout mice for which serum albumin was reduced to a similar extent as in patients with severe hypoalbuminemia. HA also led to a shorter half-life of OTA in renal capillaries, increased glomerular filtration, and to enhanced uptake of OTA into tubular epithelial cells. In conclusion, the results favor the 'concept-of-higher-free-fraction' in HA; accordingly, HA causes an increased tissue uptake of compounds with high albumin binding and increased organ toxicity. It should be studied if this concept can be generalized to all compounds with high plasma albumin binding that are substrates of hepatocyte and renal tubular epithelial cell carriers.

Journal ArticleDOI
TL;DR: In this article , the applicability of serum albumin-hyaluronic acid (HyA) conjugates as potential drug delivery colloidal particles having d ∼ 220 − 260 nm average size has been presented for encapsulation of ibuprofen (IBU).

Journal ArticleDOI
TL;DR: In this paper , a mathematical model was developed to predict the rates of albumin uptake in mouse proximal tubule sub-segments in normal and nephrotic states, and partially accounts for competition by β2 -microglobulin (β2m) and immunoglobulin G (IgG).
Abstract: Recent studies indicate that filtered albumin is retrieved in the proximal tubule (PT) via three pathways: receptor-mediated endocytosis via cubilin (high affinity) and megalin (low affinity), and fluid-phase uptake. Expression of megalin is required to maintain all three pathways, making it challenging to determine their respective contributions. Moreover, uptake of filtered molecules varies between the sub-segments (S1, S2 and S3) that make up the PT. Here we used new and published data to develop a mathematical model that predicts the rates of albumin uptake in mouse PT sub-segments in normal and nephrotic states, and partially accounts for competition by β2 -microglobulin (β2m) and immunoglobulin G (IgG). Our simulations indicate that receptor-mediated, rather than fluid-phase, uptake accounts for the vast majority of ligand recovery. Our model predicts that ∼75% of normally filtered albumin is reabsorbed via cubilin; however, megalin-mediated uptake predominates under nephrotic conditions. Our results also suggest that ∼80% of albumin is normally recovered in S1, whereas nephrotic conditions or knockout of cubilin shifts the bulk of albumin uptake to S2. The model predicts β2m and IgG axial recovery profiles qualitatively similar to those of albumin under normal conditions. In contrast with albumin, however, the bulk of IgG and β2m uptake still occurs in S1 under nephrotic conditions. Overall, our model provides a kinetic rationale for why tubular proteinuria can occur even though a large excess in potential PT uptake capacity exists, and suggests testable predictions to expand our understanding of the recovery profile of filtered proteins along the PT. KEY POINTS: We used new and published data to develop a mathematical model that predicts the profile of albumin uptake in the mouse proximal tubule in normal and nephrotic states, and partially accounts for competitive inhibition of uptake by normally filtered and pathological ligands. Three pathways, consisting of high-affinity uptake by cubilin receptors, low-affinity uptake by megalin receptors and fluid phase uptake, contribute to the overall retrieval of filtered proteins. The axial profile and efficiency of protein uptake depend on the initial filtrate composition and the individual protein affinities for megalin and cubilin. Under normal conditions, the majority of albumin is retrieved in sub-segment S1 but shifts to sub-segment S2 under nephrotic conditions. Other proteins exhibit different uptake profiles. Our model explains how tubular proteinuria can occur despite a large excess in potential proximal tubule uptake capacity.

Journal ArticleDOI
TL;DR: 61 novel post-translational modifications of human serum albumin are identified by mass spectrometry, with three-dimensional modeling showing the location of these PTMs in the regions involved in interactions of the albumin with drugs, metals, and fatty acids.
Abstract: AIM Identify novel post-translational modifications in human serum albumin. BACKGROUND Serum albumin is the most abundant protein in plasma, has many physiological functions, and is in contact with most of the cells and tissues of the human body. Post-translational modifications (PTMs) may affect functions, stability, and localization of albumin. OBJECTIVE Identify novel PTMs in human serum albumin by mass spectrometry. METHODS Human serum albumin (HSA) was used for tryptic digestion in-solution or in-gel. Mass spectrometry was applied to identify PTMs in HSA. 3-dimensional modeling was applied to explore potential impact of PTMs on known functions of albumin. RESULTS Here we report the identification of 61 novel PTMs of human serum albumin. Phosphorylation, glycosylation, nitrosylation, deamidation, methylation, acetylation, palmitoylation, geranylation, and farnesylation are examples of the identified PTMs. Mass spectrometry was used for the identification of PTMs in a purified HSA and HSA from the human plasma. Three-dimensional modeling of albumin with selected PTMs showed the location of these PTMs in the regions involved in interactions of the albumin with drugs, metals, and fatty acids. The location of PTMs in these regions may modify the binding capacity of albumin. CONCLUSION This report adds 61 novel PTMs to the catalog of human albumin.