Activities of serine

The major point of entry for one-carbon fragments into substimted folates is methylene tetrahydrofolate (Figure 45-16), which is formed by the reaction of glycine, serine, and choHne with tetrahydrofolate. Serine is the most important source of substituted folates for biosynthetic reactions, and the activity of serine hy-... 

Lactamases (EC 3.5.2.6) inactivate /3-lactam antibiotics by hydrolyzing the amide bond (Fig. 5.1, Pathway b). These enzymes are the most important ones in the bacterial defense against /3-lactam antibiotics [15]. On the basis of catalytic mechanism, /3-lactamases can be subdivided into two major groups, namely Zn2+-containing metalloproteins (class B), and active-serine enzymes, which are subdivided into classes A, C, and D based on their amino acid sequences (see Chapt. 2). The metallo-enzymes are produced by only a relatively small number of pathogenic strains, but represent a potential threat for the future. Indeed, they are able to hydrolyze efficiently carbape-nems, which generally escape the activity of the more common serine-/3-lac-tamases [16] [17]. At present, however, most of the resistance of bacteria to /3-lactam antibiotics is due to the activity of serine-/3-lactamases. These enzymes hydrolyze the /3-lactam moiety via an acyl-enzyme intermediate similar to that formed by transpeptidases. The difference in the catalytic pathways of the two enzymes is merely quantitative (Fig. 5.1, Pathways a and b). 

Buratta, S., Migliorati, G., Marchetti, C., Mambrini, R., Riccardi, C., and Mozzi, R., 2000, Dexamethasone increases the incorporation of [3H]serine into phosphatidylserine and the activity of serine base exchange enzyme in mouse thymocytes a possible relation between serine base exchange enzyme and apoptosis. MoZ. Cell. Biochem. 211 61-67. 

Factor VIII (F8) and Factor V (F5) are key regulatory elements of the blood coagulation cascade of sequential proteolytic activation of serine... 

In vitamin Be-deflcient experimental animals, there are skin lesions (e.g., acrodynia in the rat) and fissures or ulceration at the corners of the mouth and over the tongue, as well as a number of endocrine abnormalities defects in the metabolism of tryptophan (Section 9.5.4), methionine (Section 9.5.5), and other amino acids hypochromic microcytic anemia (the first step of heme biosynthesis is pyridoxal phosphate dependent) changes in leukocyte count and activity a tendency to epileptiform convulsions and peripheral nervous system damage resulting in ataxia and sensory neuropathy. There is also impairment of immune responses, as a result of reduced activity of serine hydroxymethyltransferase and hence reduced availability of one-carbon substituted folate for nucleic acid synthesis (Section 10.3.3). It has been suggested... 

Serine Hydroxymethyltransferase Serinehydroxymethyltrans-ferase is a pyridoxed phosphate-dependent aldolase that catalyzes the cleavage of serine to glycine and methylene-tetrahydrofolate (as shown in Figure 10.5). Serine is the major source of one-carbon substituted folates for biosynthetic reactions. At times of increeised cell proliferation, the activities of serine hydroxymethyltransferase emd the enzymes of the serine biosynthetic pathway cue increased. The other product of the reaction, glycine, is also required in increased cimounts under these conditions (for de novo synthesis of purines). 

Insulin could also promote glycogen synthesis by activating glycogen synthase phosphatase, rather than inactivating glycogen synthase kinase. However, a pathway linking insulin receptor activation to the activation of serine/threonine phosphatases of the PPl type has not yet been identified. 

HPR-mediated leukemia cell c)4otoxicity is triggered by ceramide-induced mitochondrial oxidative stress and is regulated downstream by Bcl-2. Free Radical Res. 2007 41 591-601. Wang H, Maurer BJ, Reynolds CP, Cabot MC. N-(4-Hydroxyphenyl)retinamide elevates ceramide in neuroblastoma cell lines by coordinate activation of serine palmitoyltransferase and ceramide synthase. Cancer Res. 2001 61 5102-5105. Bandhuvula P, Tam YY, Oskouian B, Saba JD. The immune modulator FTY720 inhibits sphingosine-1-phosphate lyase activity. J. Biol. Chem. 2005 280 33697-33700. 

Cytosolic Ca can modulate the activity of serine/threonine CaMKs via calmodulin. For instance, neuronal CaMK stimulates phosphorylation and activates tyrosine hydroxylase, the limiting enzyme in the synthesis of catecholamine neurotransmitters. Ca also regulates the activation of the conventional PKC isoforms. Increased Ca " promotes binding of Ca " to... 

Chalfant CE, Szulc Z, Roddy P et al (2004) The structural requirements for ceramide activation of serine-threonine protein phosphatases. J Lipid Res 45 496-506... 

Broos, J., Sakodinskaya, I. K., Engbersen, J. E. J., and Reinhoudt, D. N., Large activation of serine proteases by pretreatment with crown ethers, J. Chem. Soc. Chem. Comm., 255-256, 1995. 

Selective inhibition of individual proteases of the coagulation cascade may have enormous therapeutic value but is extremely difficult. Danis et al. isolated a peptide that non-com-petitively inhibits the activity of serine protease factor Vila (FVIIa), a key regulator of the coagulation cascade with a high degree of specificity and potency (120). Extensive structure-function characterization showed that the peptide binds to a previously unknown... 

Wang, H., Maurer, B.J., Reynolds, C.P., and Cabot, M.C. N-(4-hydroxyphenyl)retinamide elevates ceramide in neuroblastoma cell lines by coordinate activation of serine palmitoyltransferase and ceramide synthase. Cancer Res, 61, 2001, 5102-5105. 

In bacteria, cysteine regulates its own synthesis by feedback inhibition of serine acetyltransferase and by repression of the synthesis of cysteine synthase (Umbarger, 1978). In plants, neither ofthese effects have been observed. To attain a 44% inhibition of serine acetyltransferase from kidney bean seedlings, 0.5 mM L-cysteine was required (Smith and Thompson, 1971), a concentration 500 times greater than that required to inhibit the bacterial enzyme by 85% (Kredich and Tomkins, 1966). The activities of serine acetyltransferase in the roots of kidney beans growing either under conditions of sulfur deficiency or with adequate sulfate nutrition were not significantly... 

Labow RS, Meek E, Santerre IP. The biodegradation of poly(urethane)s by the estero-lytic activity of serine proteases and oxidative enzyme systems. 1 Biomater Sci Polym Ed 1999 10(7) 699-713. 

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