Serine degradation

The enzyme serine hydroxymethyltransferase requires pyridoxal phosphate as cofactor. Propose a mechanism for the reaction catalyzed by this enzyme, in the direction of serine degradation (glycine production). (Hint See Figs 18-19 and 18-20b.)... 

M. Watanabe, Y. Morinaga, T, Takenouchi, and H. Enei, Efficient conversion of glycine to L-serine by a glycine-resistant mutant of ahnethylotroph using Co as an inhibitor of L-serine degradation, /. Ferment. Techno., 65 563 (1987). 

Fig. 39.5. The major pathway for serine synthesis from glucose is on the left, and for serine degradation on the right. Serine levels are maintained because serine causes repression (circled 4-) of 3-phosphoglycerate dehydrogenase synthesis. Serine also inhibits (circled -) phosphoser-ine phosphatase.

A possible minor route of serine degradation could be via the conversion of serine to O-acetyl serine by serine transacetylase which has been partially purified from kidney bean seedlings by Smith and Thompson (1971). O-acetyl... 

A number of investigators have attempted to determine the major pathways of serine catabolism from distribution of the C Mabel of isotopic serine in glycogen and other amino acids in the intact rat (47, 4S) and in a variety of products in rat liver slices (49). The results indicated that the metabolic pathways of L-serine and D-serine are quite distinct. In other respects there is no general agreement. Koeppe and co-workers (47, 4S) determined that conversion to pyruvate is an important pathway of L-serine degradation, while an important product of unknown nature is formed as an intermediate from D-serine. Elwyn et al. (49) concluded that conversion to glycine is probably the major pathway for L-serine metabolism. 

Protein G. This vitamin K-dependent glycoproteia serine protease zymogen is produced ia the Hver. It is an anticoagulant with species specificity (19—21). Proteia C is activated to Proteia by thrombomodulin, a proteia that resides on the surface of endothefial cells, plus thrombin ia the presence of calcium. In its active form, Proteia selectively iaactivates, by proteolytic degradation. Factors V, Va, VIII, and Villa. In this reaction the efficiency of Proteia is enhanced by complex formation with free Proteia S. la additioa, Proteia activates tissue plasminogen activator, which... 

Activated Proteia C (C ) [42617-41 -4] (19—21) is a aaturaHy occurring serine protease that, ia combination with free Proteia S, degrades and iaactivates Factors V, Va, VIII, and Villa. By degradation of these factors the blood becomes anticoagulated and thus may be a useful therapeutic agent. 

Serpins form very tight complexes with their corresponding serine pro-teinases, thereby inhibiting the latter. A flexible loop region of the serpin binds to the active site of the proteinases. Upon release of the serpin from the complex its polypeptide chain is cleaved by the proteinase in the middle of this loop region and the molecule is subsequently degraded. In addition to the active and cleaved states of the serpins there is also a latent state with an intact polypeptide chain that is functionally inactive and does not bind to the proteinase. 

Design your own degradative pathway. You know the rules (organic mechanisms), and you ve seen the kinds of reactions that occur in the biological degradation of fats and carbohydrates inLo acetyl CoA. If you were Mother Nature, what series of steps would you use to degrade the amino acid serine into acetyl CoA ... 

Cathepsins are intracellular proteinases that reside within lysosomes or specific intracellular granules. Cathepsins are used to degrade proteins or pqffides that are internalised from the extracellular space. Some cathepsins such as cathepsin-G or cathepsin-K may be released from the cell to degrade specific extracellular matrix proteins. All cathepsins except cathepsin-G (serine) and cathepsin-D (aspartyl) are cysteine proteinases. 

The quantification of kinins in human tissues or body fluids has been limited due to the inherent difficulties in accurately measuring the concentration of ephemeral peptides. Today HPLC-based and RIA/capture-ELA measurements are established to determine kinins in human plasma, liquor or mine. Serine protease inhibitors need to be added to prevent rapid degradation of the kinins in vitro during sample preparation. Kinins and their degradation products have been studied in various biological milieus such as plasma/ serum, urine, joint fluids, kidney, lung and skeletal muscle [2]. Under normal conditions, the concentration of kinins in these compartments is extremely low for... 

Plasmin, a serine protease (83 kDa), can degrade fibrin, and its degradation products (FDP) are soluble in the blood. Plasmin is formed from its proenzyme (zymogen, precursor), plasminogen (92 kDa), synthesized by the liver, and secreted into the blood circulation, where its concentration is 2 pM. Plasminogen is converted to plasmin by plasminogen activators (serine proteases). 

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