Human blood is composed of 44%
red blood cells,1% white blood cells and 55%
plasma(血浆；淋巴液).Plasma consists of 91% water,7% proteins and 2% salts.It
contains more than 120 different proteins,including
albumin(清蛋白，白蛋白)(HAS),immunoglobulin
G(IgG),fibrinogen(血纤维蛋白原)(factor Ⅰ),alpha-2-macroglobulin(巨球蛋白)(α
2M),alpha-1-antitrypsin(抗胰蛋白酶)(A1AT),transferrin(铁传递蛋白)(siderophilin) and lipoproteins and
numerous proteolytic enzymes,such as esterases and
peptideases.
新浪博客
According to the enzyme classification(E.C.)
( www.biochem.ucl.ac.uk/bsm/enzymes/ec3/index.html, www.ebi.ac.uk/thornton-srv/databases/enzymes/ ).
Numerous human proteolytic enzymes(peptideases) are involved in peptide degradation.The greatest threat to peptides lies in the lumen(管,腔)of the small intestine,which contains gram quantities of peptideases secreted from the pancreas(胰腺)(e.g. α-chymotrypsin(胰凝乳蛋白酶，糜蛋白酶),trypsin(胰朊酶，胰蛋白酶),pancreatic elastase(胰弹性蛋白酶),carboxypeptideases A,B,D,N,and U and so on),as well as cellular peptideases from mucosal cells.The second major enzymatic barrier is the brush border(刷毛边层)membrane of the epithelial(上皮的)cells,which contains at least 15 peptideases(e.g. dipeptidyl-peptidase IV,prolyl tripeptidyl-peptidase,angiotensin-converting enzyme(血管紧张素转化酶),leucyl-aminopeptidase,aminopeptidease M,aminopeptidease A,neprilysin and so on),that together have a broad specificity and can degrade both peptides.Lysosomal (溶酶体的)peptideases(leukocyte elastase(白细胞弹性蛋白酶),cathepsins(组织蛋白酶) B and D and so on) will also target peptides endocytosed by epithelial(上皮的)or endothelial(内皮的)cells. In the matrix metalloproteinase(金属蛋白酶)family(zinc-dependant endopeptidases) known to degrade extracellular matrix proteins,interstitial collagenase(MMP-1,E.C.3.4.24.7) is also able to cleave specific small molecules such as peptides. Amongst proteases,carboxypeptidease C – sometimes referred to as Y(E.C.3.4.16.5) – is the only enzyme that exhibits both the esterase and the amidase activities typical of serine proteases.Many enzymes are also present in different tissues or organs. For example,in brain micro-capillaries,which constitute part of the blood-brain barrier(BBB),gamma-glutamyl transpeptidease(transferase,E.C.2.3.2.2),alkaline phosphatase(碱性磷酸酯酶)(hydrolase,E.C.3.1.3.1),monoamine oxidase(oxidoreductase,E.C.1.4.3.4),catechol-O-methyl transferase(儿茶酚氧位甲基移位酶)(transferase,E.C.2.1.1.6),butyrylcholinesterase(hydrolase(水解酶类),E.C.3.1.1.8) and aromatic-L-amino acid decarboxylase;lyase,are found at high levels.Other enzymes,such as epoxidehydrolase(or epoxide hydrolase;hydrolase,E.C.3.3.2.9,former E.C.3.3.2.3),UDP-glucuronosyl-transferase(glycosyl-transferase),benzyloxyresorufin-O-deethylase(cytochrome(细胞色素)P-450 CYP2B1;oxidoreductase(氧化还原酶)and glutathione-S-transferase are also found bound to brain micro-capillaries at high levels.The protein-disulfide reductase(oxidoreductase),which enalbles disulfide bridge cleavage by reduction in dithiol,is also abundant in the brain and can alter peptides structures stable in plasma.
Proteolytic peptide degradation,which results in short half-life(generally,a few minutes or ,at best,a few hours), can be countered in various ways,in particular by using new synthetic strategies for limiting metabolism and alternative routes of administration.
Table 1 Most important human proteolytic enzymes involved in peptide degradation
| Enzymes |
E.C. Number |
Cleavage sites |
| Serine proteases |
E.C.3.4.21. |
|
| α-chymotrypsin(胰凝乳蛋白酶，糜蛋白酶) |
E.C.3.4.21.1 |
Tyr-|-Xaa, Trp-|-Xaa, Phe-|-Xaa, and also Leu-|-Xaa,
Met-|-Xaa, |
| Trypsin (胰朊酶，胰蛋白酶) |
E.C.3.4.21.4 |
Arg-|-Xaa, Lys-|-Xaa, |
| Pancreatic elastase(胰弹性蛋白酶) |
E.C.3.4.21.36 |
Ala-|-Xaa,and
also Gly-|-Xaa, Val-|-Xaa, Ser-|-Xaa, |
| Thrombin(凝血酶) |
E.C.3.4.21.5 |
Arg-|-Gly, |
| Plasmin(胞质素，胞浆素) |
E.C.3.4.21.7 |
Lys-|-Xaa,>
Arg-|-Xaa |
| Prolyl oligopeptidase,or prolyl
endopeptidase |
E.C.3.4.21.26 |
Pro-|-Xaa,>> Ala-|-Xaa |
| Plasma kallikrein(血浆激肽释放酶) |
E.C.3.4.21.34 |
Arg-|-Xaa, Lys-|-Xaa,including Arg-|-Ser,
Lys-|-Arg, |
| Leukocyte elastase(白细胞弹性蛋白酶 ),or neutrophil elastase(中性白细胞弹性蛋白酶),or lysosomal elastase(溶酶体弹性蛋白酶) |
E.C.3.4.21.37 |
Val-|-Xaa, Ala-|-Xaa, |
| Cysteine proteases |
E.C.3.4.22. |
|
| Cathepsin B(组织蛋白酶) |
E.C.3.4.22.1 |
Arg-Arg-|-Xaa, and also Leu-|-Xaa, Ala-|-Xaa, Phe-|-Xaa,
Trp-|-Xaa, |
| Clostripain(梭菌蛋白酶),or endoproteinase Arg-C |
E.C.3.4.22.8 |