C H A P T E R 3 6 , F I G U R E 17
Structure of heparin. Heparin is a polymer of repeating disaccharide units that con-
tain one uronic acid and one hexosamine residue. The uronic acid residues may be either glucuronic acid or iduronic
acid, both of which are monosaccharide acids that differ in their stereochemistry. The hexosamine residue is glu-
cosamine. Both the uronic and hexosamine residues can be modified by O- and N-sulfation and the glucosamine
residue by N-acetylation. All heparins bind to antithrombin; however, heparin molecules that contain a unique pen-
tasaccharide sequence bind with particularly high affinity (high-affinity heparins). Approximately 30% of the heparin
molecules present in the commonly used therapeutic heparins have high affinity for antithrombin.
C H A P T E R 3 6 , F IG U R E 1 8
Plasminogen activation. Plasminogen is converted to plasmin as the result of cleav-
ing a single peptide bond, Arg561-Val562. The molecular mechanism of transforming the zymogen into its active form
is the same as the activation of trypsinogen to trypsin. Two different proteinases are responsible for the physiological
activation of plasminogen: tissue-type plasminogen activator (t-PA) and urinary plasminogen activator (u-PA). t-PA is
the principle activator of plasminogen and is synthesized primarily in endothelial cells which are the principle source
of t-PA in the circulating blood. t-PA is present in high concentrations in uterine tissue and in various malignant cells.
u-PA is found in the kidney and may be particularly important in preventing the accumulation of fibrin in the
glomeruli. In the circulation, more than one-half of the t-PA is in a complex with PAI-1. The activation of plasmino-
gen is accompanied by the proteolytic action of plasmin on plasminogen at Arg68-Met69 and at Lys77-Lys78. This reac-
tion results in the formation of a derivative of plasminogen in which the first 77 amino acids at the N-terminal end of
the molecule are removed. This derivative of plasminogen,
lys p la sm in o g en
, is activated more rapidly than the native,
g lu p la sm in o g en .
Motifs and domains are color coded as follows: kringle domains (orange), EGF-like domain
(magenta), activation peptide (yellow), and proteinase domain (green). Light chains are indicated in dark gray, heavy
chains in light gray. Regions connecting the motifs are black.