Sunday 27 May 2012

Heparin structure


Native heparin is a polymer with a atomic weight alignment from 3 kDa to 30 kDa, although the boilerplate atomic weight of a lot of bartering heparin affairs is in the ambit of 12 kDa to 15 kDa.5 Heparin is a affiliate of the glycosaminoglycan ancestors of carbohydrates (which includes the carefully accompanying atom heparan sulfate) and consists of a variably sulfated repeating disaccharide unit.6 The capital disaccharide units that action in heparin are apparent below. The a lot of accepted disaccharide assemblage is composed of a 2-O-sulfated iduronic acerbic and 6-O-sulfated, N-sulfated glucosamine, IdoA(2S)-GlcNS(6S). For example, this makes up 85% of heparins from beef lung and about 75% of those from beefy abdominal mucosa.7 Not apparent beneath are the attenuate disaccharides absolute a 3-O-sulfated glucosamine (GlcNS(3S,6S)) or a chargeless amine accumulation (GlcNH3+). Under physiological conditions, the ester and amide sulfate groups are deprotonated and allure absolutely answerable counterions to anatomy a heparin salt. It is in this anatomy that heparin is usually administered as an anticoagulant.

One assemblage of heparin (the "Howell Unit") is an bulk about agnate to 0.002 mg of authentic heparin, which is the abundance appropriate to accumulate 1 mL of cat's claret aqueous for 24 hours at 0 °C.8

GlcA-GlcNAc

GlcA-GlcNS

IdoA-GlcNS

IdoA(2S)-GlcNS

IdoA-GlcNS(6S)

IdoA(2S)-GlcNS(6S)

editAbbreviations

GlcA = β-D-glucuronic acid

IdoA = α-L-iduronic acid

IdoA(2S) = 2-O-sulfo-α-L-iduronic acid

GlcNAc = 2-deoxy-2-acetamido-α-D-glucopyranosyl

GlcNS = 2-deoxy-2-sulfamido-α-D-glucopyranosyl

GlcNS(6S) = 2-deoxy-2-sulfamido-α-D-glucopyranosyl-6-O-sulfate

editThree-dimensional structure

The three-dimensional anatomy of heparin is complicated by the actuality that iduronic acerbic may be present in either of two low-energy conformations if internally positioned aural an oligosaccharide. The conformational calm is afflicted by sulfation accompaniment of adjoining glucosamine sugars.9 Nevertheless, the band-aid anatomy of a heparin dodecasaccharide composed alone of six GlcNS(6S)-IdoA(2S) echo units has been bent application a aggregate of NMR spectroscopy and atomic clay techniques.10 Two models were constructed, one in which all IdoA(2S) were in the 2S0 anatomy (A and B below), and one in which they are in the 1C4 anatomy (C and D below). However there is no affirmation to advance that changes amid these conformations action in a concerted fashion. These models accord to the protein abstracts coffer cipher 1HPN.

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