Biochemistry blood clotting

Scully MR The biochemistry of blood clotting The digestion of a liquid to form a solid. Essays in Biochem 1992 27 17-36. 

In the past several decades, modem biochemistry has elucidated all or most of the components of a number of biochemical systems. In the next five chapters I will discuss a few of them. In Chapter 3 I will look at a fascinating structure called a cilium, which some cells use to swim. In the next chapter I will discuss what happens when you cut your finger— and show that the apparent simplicity of blood clotting is deceptively complicated. After that I will consider how cells transport materials from one subcellular compartment to another, encountering many of the same problems that Federal Express meets in delivering... 

The impotence of Darwinian theory in accounting for the molecular basis of life is evident not only from the analyses in this book, but also from the complete absence in the professional scientific literature of any detailed models by which complex biochemical systems could have been produced, as shown in Chapter 8. In the face of the enormous complexity that modern biochemistry has uncovered in the cell, the scientific community is paralyzed. No one at Harvard University, no one at the National Institutes of Health, no member of the National Academy of Sciences, no Nobel prize winner—no one at all can give a detailed account of how the cilium, or vision, or blood clotting, or any complex biochemical process might have developed in a Darwinian fashion. But we are here. Plants and animals are here. The complex systems are here. All these things got here somehow if not in a Darwinian fashion, then how ... 

Voet, D. and Voet, X G. (1995) Biochemistry, 2nd edition, Chaps. 24, 30 and 34. (Amino add metabolism, protein biosynthesis, blood clotting, peptide hormones and neurotransmitters). 

Fig. 11.4 Mechanism of clotting factor localization to an activated platelet surface. Left After synthesis in the liver, certain blood clotting proteins are posttranslationally modified in the endoplasmic reticulum by a vitamin K-dependent Vit K carboxylase. This enzyme forms carboxyglutamate residues (top center) that chelate calcium ions. Right In the bloodstream, clotting factor-bound calcium ions attach to negatively charged phosphatidylserine that appears on the surface of activated platelets. Certain therapeutic drugs or acquired deficiencies inhibit this process - see text (Original figure submitted by Dr Paul DeAngelis, Department of Biochemistry, University of Oklahoma HSC, Oklahoma City, OK, USA)...

As for the biochemistry involved, it has been proposed that the L-arginine to nitric oxide metabolic pathway is activated, whereby the greater amount of nittic oxide produced is cytotoxic to cancer cells. Not only this, bnt the nitric oxide produces a greater vascular blood flow, and the enzyme streptokinase naturally present in the toxins may lyse or destroy blood clots. Another beneficial effect was apparently against osteoarthritis. 

The adsorption of proteins on the surface of glass is well known in many areas of biochemistry (l.- 3) For example, blood clotting is promoted on glass surfaces, and siliconization is used to minimize this effect. Clotting starts when factor XII is activated by the anionic charge of the silanol groups on the glass surface (4-5). 

Streptokinase, an extracellular protein (415 aa, Mr 47 kDa) produced by various strains of /3-hemolytic streptococci. Streptokinase is not generally considered to be a proteolytic enzyme, but is one of the most potent exogenous activators of human plasminogen. Complexes of streptokinase with human plasminogen can hydrolytically activate other plasminogen molecules to plasmin which then dissolves blood clots alone [L. A. Schick, F. J. Castellino, Biochem. Biophys. Res. Commun. 1974, 57, 47 K. W. Jackson, J. Tang, Biochemistry 1982, 21, 6620]. 

Lovelock JE, Porterfield BM (1952) Blood clotting the function of electrolytes and of calcium. Biochemistry 50 415-420... 

In mammals and birds vitamin K] is an essential cofactor in the posttranslational carboxy lation reaction of glutamic acid residues (GLU) to y-carboxygiutamic acid residues (GLA) in a number of blood clotting factors (factors II, VII, IX, and X) and also in some other proteins, such as protein C, protein S and osteocalcin. These GLA residues provide the proteins with calcium-binding properties essential for the interaction with phospholipids and for their activation. Excellent articles and reviews on the biochemistry and on the physiological role of vitamin Kj in humans are given by Suttie (70), Friedman (71), and Friedrich (72). Besides vitamin K itself, ubiquinones and plastoquinones also occur in higher plants. Structures of vitamin Ki and of some of these related compounds are presented in Fig. 7. 

Obtain 3 liters of fresh pig blood (see Supplies and Reagents section for an alternative supply of blood, if necessary) and immediately mix with heparin sulfate (30 mg/liter final concentration) to prevent clotting. Place the blood in an ice bucket and proceed. All additional steps through step 6 should be performed at 4°C. We suggest that steps 1 to 6 be performed by the instructor prior to the beginning of the experiment. If you plan to perform Experiment 16 (Experiments in Clinical Biochemistry and Metabolism ) in conjunction with this experiment, a... 

Martin, D. W. (1983). Blood plasma and clotting. In Harper s review of Biochemistry, pp.635,20 ed. Medical publication, Los Anglos, California. 

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