protein binding

• タンパク質結合、タンパク結合、蛋白結合

WordNet

1. executed with proper legal authority; "a binding contract"
2. the protective covering on the front, back, and spine of a book; "the book had a leather binding" (同)book binding, cover, back
3. strip sewn over or along an edge for reinforcement or decoration
4. the capacity to attract and hold something
5. any of a large group of nitrogenous organic compounds that are essential constituents of living cells; consist of polymers of amino acids; essential in the diet of animals for growth and for repair of tissues; can be obtained from meat and eggs and milk and legumes; "a diet high in protein"

PrepTutorEJDIC

1. 義務的な,拘束力ある / 〈U〉しばること;〈C〉しばる物 / 〈C〉製本,装丁 / 〈U〉縁(‘ふち')取り材料
2. 蛋白(たんばく)質

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/07/24 11:56:22」(JST)

wiki en

[Wiki en表示]

A drug's efficiency may be affected by the degree to which it binds to the proteins within blood plasma. The less bound a drug is, the more efficiently it can traverse cell membranes or diffuse. Common blood proteins that drugs bind to are human serum albumin, lipoprotein, glycoprotein, and α, β‚ and γ globulins.

Binding

A drug in blood exists in two forms: bound and unbound. Depending on a specific drug's affinity for plasma protein, a proportion of the drug may become bound to plasma proteins, with the remainder being unbound. If the protein binding is reversible, then a chemical equilibrium will exist between the bound and unbound states, such that:

Protein + drug ⇌ Protein-drug complex

Notably, it is the unbound fraction which exhibits pharmacologic effects. It is also the fraction that may be metabolized and/or excreted. For example, the "fraction bound" of the anticoagulant warfarin is 97%. This means that of the amount of warfarin in the blood, 97% is bound to plasma proteins. The remaining 3% (the fraction unbound) is the fraction that is actually active and may be excreted.

Protein binding can influence the drug's biological half-life in the body. The bound portion may act as a reservoir or depot from which the drug is slowly released as the unbound form. Since the unbound form is being metabolized and/or excreted from the body, the bound fraction will be released in order to maintain equilibrium.

Since albumin is alkalotic, acidic and neutral drugs will primarily bind to albumin. If albumin becomes saturated, then these drugs will bind to lipoprotein. Basic drugs will bind to the acidic alpha-1 acid glycoprotein. This is significant because various medical conditions may affect the levels of albumin, alpha-1 acid glycoprotein, and lipoproteins.

Impact of the altered protein binding

Only the unbound fraction of the drug undergoes metabolism in the liver and other tissues. As the drug dissociates from the protein more and more drug undergoes metabolism. Changes in the levels of free drug change the volume of distribution because free drug may distribute into the tissues leading to a decrease in plasma concentration profile. For the drugs which rapidly undergo metabolism, clearance is dependent on the hepatic blood flow. For drugs which slowly undergo metabolism, changes in the unbound fraction of the drug directly change the clearance of the drug.

Note: The most commonly used methods for measuring drug concentration levels in the plasma measure bound as well as unbound fractions of the drug.

The fraction unbound can be altered by a number of variables, such as the concentration of drug in the body, the amount and quality of plasma protein, and other drugs that bind to plasma proteins. Higher drug concentrations would lead to a higher fraction unbound, because the plasma protein would be saturated with drug and any excess drug would be unbound. If the amount of plasma protein is decreased (such as in catabolism, malnutrition, liver disease, renal disease), there would also be a higher fraction unbound. Additionally, the quality of the plasma protein may affect how many drug-binding sites there are on the protein.

Drug interactions

Using 2 drugs at the same time may affect each other's fraction unbound. For example, assume that Drug A and Drug B are both protein-bound drugs. If Drug A is given, it will bind to the plasma proteins in the blood. If Drug B is also given, it can displace Drug A from the protein, thereby increasing Drug A's fraction unbound. This may increase the effects of Drug A, since only the unbound fraction may exhibit activity.

	Before Displacement	After Displacement	% increase in unbound fraction
Drug A
% bound	95	90
% unbound	5	10	+100
Drug B
% bound	50	45
% unbound	50	55	+10

Note that for Drug A, the % increase in unbound fraction is 100% – hence, Drug A's pharmacological effect can potentially double (depending on whether the free molecules get to their target before they are eliminated by metabolism or excretion). This change in pharmacologic effect could have adverse consequences.

This effect of protein binding is most significant with drugs that are highly protein-bound (>95%) and have a low therapeutic index, such as warfarin. A low therapeutic index indicates that there is a high risk of toxicity when using the drug. Since warfarin is an anticoagulant with a low therapeutic index, warfarin may cause bleeding if the correct degree of pharmacologic effect is not maintained. If a patient on warfarin takes another drug that displaces warfarin from plasma protein, such as a sulfonamide antibiotic, it could result in an increased risk of bleeding.

Plasma protein binding prediction software

• Quantum Plasma Protein Binding
• S+ Plasma Protein Binding
• Albumin binding prediction

See also

• Pharmacokinetics
• Blood proteins

References

1. Shargel, Leon (2005). Applied Biopharmaceutics & Pharmacokinetics. New York: McGraw-Hill, Medical Pub. Division. ISBN 0-07-137550-3. 

External links

• The measurement of Plasma Protein Binding The performance of plasma protein binding studies including analysis of the data.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 鉄のバランス調節 regulation of iron balance
• 2. 肥大型心筋症の遺伝学 genetics of hypertrophic cardiomyopathy
• 3. プロテインS欠乏症：臨床症状および診断 protein s deficiency clinical manifestations and diagnosis
• 4. メチシリン耐性黄色ブドウ球菌の微生物学 microbiology of methicillin resistant staphylococcus aureus
• 5. 妊娠37週未満の前期（陣痛開始前）破水 preterm premature prelabor rupture of membranes

English Journal

• Rapid preparation of mutated influenza hemagglutinins for influenza virus pandemic prevention.

• Nishioka R1, Satomura A2,3, Yamada J4, Kuroda K5, Ueda M6.
• AMB Express.AMB Express.2016 Dec;6(1):8. doi: 10.1186/s13568-016-0179-y. Epub 2016 Jan 21.
• Influenza viruses have periodically caused pandemic due to frequent mutation of viral proteins. Influenza viruses have two major membrane glycoproteins: hemagglutinin (HA) and neuraminidase (NA). Hemagglutinin plays a crucial role in viral entry, while NA is involved in the process of a viral escape
• PMID 26797882

• PIWIL1 Is Expressed in the Canine Testis, Increases with Sexual Maturity, and Binds Small RNAs.

• Stalker L1, Russell SJ1, Co C1, Foster RA2, LaMarre J3.
• Biology of reproduction.Biol Reprod.2016 Dec;94(1):17. doi: 10.1095/biolreprod.115.131854. Epub 2015 Dec 9.
• Spermatogenesis is a highly regulated process leading to the development of functional spermatozoa through meiotic division and subsequent maturation. Recent studies have suggested that a novel class of Argonaute proteins, known as the PIWI clade, plays important roles in multiple stages of spermato
• PMID 26658707

• Preclinical imaging of the co-stimulatory molecules CD80 and CD86 with indium-111-labeled belatacept in atherosclerosis.

• Meletta R1, Müller Herde A1, Dennler P2, Fischer E2, Schibli R1,2, Krämer SD3.
• EJNMMI research.EJNMMI Res.2016 Dec;6(1):1. doi: 10.1186/s13550-015-0157-4. Epub 2016 Jan 4.
• BACKGROUND: The inflammatory nature of atherosclerosis provides a broad range of potential molecular targets for atherosclerosis imaging. Growing interest is focused on targets related to plaque vulnerability such as the co-stimulatory molecules CD80 and CD86. We investigated in this preclinical pro
• PMID 26728358

Japanese Journal

• Effects of Vasoactive Intestinal Polypeptide and Forskolin on mRNA Expression of Prolactin and Prolactin Regulatory Element-Binding Protein in the Anterior Pituitary Gland of Chicken Embryo and Laying Hens

• Journal of poultry science 53(4), 313-317, 2016-10
• NAID 40020967563

• Autonomous translational pausing is required for XBP1u mRNA recruitment to the ER via the SRP pathway

• 2016-09-20
• NAID 120005850422

• Alleviation of temperature-sensitive secretion defect of Pseudomonas fluorescens ATP-binding cassette (ABC) transporter, TliDEF, by a change of single amino acid in the ABC protein, TliD

• Journal of bioscience and bioengineering 122(3), 283-286, 2016-09
• NAID 40020949775

Related Pictures

---

★リンクテーブル★

リンク元	「蛋白結合」「タンパク結合」「タンパク質結合」
拡張検索	「high density lipoprotein-binding protein」「competitive protein binding assay」
関連記事	「binding」

「蛋白結合」

　　[★]

英

protein binding

関

タンパク質結合、タンパク結合

「タンパク結合」

　　[★]

英

protein binding

関

蛋白結合、タンパク質結合

「タンパク質結合」

　　[★]

英

protein binding

関

蛋白結合、タンパク結合

「high density lipoprotein-binding protein」

　　[★]

• 高密度リ・タンパク質結合タンパク質

関

HDL-binding protein

「competitive protein binding assay」

　　[★]

同

CPBA

同

CPBA

「binding」

　　[★]

• n.

• 結合、バインディング

• adj.

• 結合性の

関

affinity、associate、bind、bond、bonding、combine、conjoin、conjugate、conjugation、conjunction、connect、connection、connective、connectivity、couple、dock、engage、engagement、join、ligate、linkage、symphysial、symphysic、union