Molecular Aspects of Human Alpha-1 Acid Glycoprotein — Structure and Function

Taguchi, Kazuaki; Nishi, Katsuhide; Chuang, Victor Tuan Giam; Maruyama, Toru; Otagiri, Masaki

doi:10.5772/56101

Cited by 28 publications

(50 citation statements)

References 114 publications

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“…AAG-A (ORM1) is polymorphic with three closely related genetic variants: F1, F2, and S, differing by <5 amino acid residues, and generally referred to as F1*S in Table V (65,66). AAG-B and AAG-B′ (ORM2) encode the genetic variant A.…”

Section: Structure and Genetics Of Human Aagmentioning

confidence: 99%

Pharmacokinetic and Pharmacodynamic Considerations for Drugs Binding to Alpha-1-Acid Glycoprotein

Smith¹,

Waters

2018

Pharm Res

110

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According to the free drug hypothesis only the unbound drug is available to act at physiological sites of action, and as such the importance of plasma protein binding primarily resides in its impact on pharmacokinetics and pharmacodynamics. Of the major plasma proteins, alpha-1-acid glycoprotein (AAG) represents an intriguing one primarily due to the high affinity, low capacity properties of this protein.In addition, there are marked species and age differences in protein expression, homology and drug binding affinity. As such, a thorough understanding of drug binding to AAG can help aid and improve the translation of pharmacokinetic/pharmacodynamic (PK/PD) relationships from preclinical species to human as well as adults to neonates. This review provides a comprehensive overview of our current understanding of the biochemistry of AAG; endogenous function, impact of disease, utility as a biomarker, and impact on PK/PD. Experimental considerations are discussed as well as recommendations for understanding the potential impact of AAG on PK through drug discovery and early development.

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Section: Structure and Genetics Of Human Aagmentioning

confidence: 99%

Pharmacokinetic and Pharmacodynamic Considerations for Drugs Binding to Alpha-1-Acid Glycoprotein

Smith¹,

Waters

2018

Pharm Res

110

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“…AGP has a highly symmetrical β-sheet structure that is comprised of an eight-stranded β-barrel [146,147,152]. This protein is believed to have one wide and flexible drug-binding region that is common for basic, acidic, and neutral drugs [150,152,153]. …”

Section: Chromatographic Studies Of Protein-based Cspsmentioning

confidence: 99%

Chromatographic Studies of Protein-Based Chiral Separations

Zheng

Azaria

et al. 2016

Separations

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The development of separation methods for the analysis and resolution of chiral drugs and solutes has been an area of ongoing interest in pharmaceutical research. The use of proteins as chiral binding agents in high-performance liquid chromatography (HPLC) has been an approach that has received particular attention in such work. This report provides an overview of proteins that have been used as binding agents to create chiral stationary phases (CSPs) and in the use of chromatographic methods to study these materials and protein-based chiral separations. The supports and methods that have been employed to prepare protein-based CSPs will also be discussed and compared. Specific types of CSPs that are considered include those that employ serum transport proteins (e.g., human serum albumin, bovine serum albumin, and alpha1-acid glycoprotein), enzymes (e.g., penicillin G acylase, cellobiohydrolases, and α-chymotrypsin) or other types of proteins (e.g., ovomucoid, antibodies, and avidin or streptavidin). The properties and applications for each type of protein and CSP will also be discussed in terms of their use in chromatography and chiral separations.

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“…The activity of AGP is, however, still not fully understood, and depending on its concentration and the cell it affects, it can have both a pro-and anti-inflammatory function [47]. The increased AGP expression facilitates LPS elimination, resulting in a protective effect against endotoxin shock derived from the infection [33]. At physiological concentrations, AGP, due to its antioxidant activity, protects erythrocytes from H 2 O 2 .…”

Section: Acute Phase Proteins' Seasonal Variationmentioning

confidence: 99%

“…At physiological concentrations, AGP, due to its antioxidant activity, protects erythrocytes from H 2 O 2 . According to these reports, an increase in the AGP content in serums above the normal value found under pathological conditions facilitates the passage of erythrocytes through capillaries, stabilizes erythrocyte membranes, and protects against oxidative stress, all of which are favorable properties for the microcirculation [33].…”

Section: Acute Phase Proteins' Seasonal Variationmentioning

confidence: 99%

“…AGP has been reported to have a protective effect against sepsis from gram-negative infections [30]. Moore et al [32] showed that AGP interacts with the bacterial lipopolysaccharide (LPS), which is an initiator of the acute inflammatory response associated with septic shock, resulting in the formation of an AGP-LPS complex [33]. Hochepied et al [30] demonstrated that AGP was effective against a lethal infection by Klebsiella pneumonia, and Shemyakinet al [34] showed its preventive and therapeutic effect in mice against Bacillus anthracis.…”

Section: Introductionmentioning

confidence: 99%

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Acute Phase Proteins and Vitamin D Seasonal Variation in End-Stage Renal Disease Patients

Maraj

Hetwer

Dumnicka

et al. 2020

JCM

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End-stage renal disease (ESRD) patients are vulnerable to vitamin D deficiency due to impaired renal hydroxylation, low dietary intake and inadequate sun exposure. Vitamin D plays a role in innate and adaptive immunity and its seasonal variation has been linked to mortality. ESRD is associated with inadequate removal of pro-inflammatory cytokines regulating acute phase protein (APP) synthesis. Our aim was to look for associations between lifestyle factors, diet, and vitamin D seasonal variation and their relationship with selected APPs and calcium-phosphate metabolism. The study included 59 ESRD patients treated with maintenance hemodialysis. A 24-hour dietary recall was conducted in the post-summer (November 2018, PS) and post-winter (February/March 2019, PW) period, and blood was collected for the measurements of serum total vitamin D, α 1 -acid glycoprotein (AGP), C-reactive protein (CRP), albumin, prealbumin (PRE), parathormone, calcium and phosphate. A self-constructed questionnaire gathered information on vitamin D supplementation, sun exposure and physical activity. Higher caloric intake was observed PW compared PS. Less than 15% of participants met the dietary recommendations for energy, protein, fiber, vitamin D and magnesium intake. Vitamin D supplementation was associated with higher serum vitamin D regardless of season. AGP, PRE, albumin, and vitamin D presented seasonal changes (higher values PS). In patients with serum vitamin D below 25 ng/mL, vitamin D seasonal change correlated with CRP and prealbumin change. Phosphate and Ca × P correlated positively with AGP. A low vitamin D serum level could impact the inflammatory process; however, more studies are needed to confirm the relationship.

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Molecular Aspects of Human Alpha-1 Acid Glycoprotein — Structure and Function

Cited by 28 publications

References 114 publications

Pharmacokinetic and Pharmacodynamic Considerations for Drugs Binding to Alpha-1-Acid Glycoprotein

Pharmacokinetic and Pharmacodynamic Considerations for Drugs Binding to Alpha-1-Acid Glycoprotein

Chromatographic Studies of Protein-Based Chiral Separations

Acute Phase Proteins and Vitamin D Seasonal Variation in End-Stage Renal Disease Patients

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