Biosynthesis in vivo

COX-2 synthesises PGI2 (prostacyclin) and the high incidence of myocardial infarctions with selective COX-2 inhibitors has been attributed to inhibition of COX-2 in vascular tissues. Prostacyclin, made by blood vessel walls, inhibits aggregation of platelets and maintains a balance with thromboxane. Thromboxane, which is released by platelets, promotes clotting. Prostacyclin is synthesised mostly by COX-1, but in humans selective COX-2 inhibition reduces its biosynthesis in vivo. This reduced synthesis may lead to an overactive thromboxane system and increased risk of thromboembolism. 

As the result of a screening program examining microbial fermentation products for pharmacological activity (other than antibiotic activity), fusaric acid (10) was isolated from Fusarium oxysporum following the discovery that extracts were potent inhibitors of dopamine p-hydroxylase, and thus interfered with the biosynthesis in vivo of the pressor neurohormone, norepinephrine. To refine this lead, amidation of 10 via the acid chloride was carried out... 

Thieno[2,3-. ]pyridine derivatives, 155, can be successfully used as replacements for the hexahydronaphthalene ring found in naturally occurring 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors <2001BML1285>. These compounds also display significant inhibition of cholesterol biosynthesis in vivo. 

The biosynthesis of the isoprenoid moiety of terpenoid alkaloids has been reviewed. It has been found ° that catharanthine (which accumulates in Vinca rosea) inhibited a membrane-bound monoxygenase that oxidized geraniol at C-10. The inhibition was reversible and non-competitive in solubilized preparations of the enzyme and hence was probably not due to disruption of membranes. Other alkaloids that were produced as end-products were less inhibitory and catharanthine may mediate feed-back control of alkaloid biosynthesis in vivo. 

Biosynthesis In vivo experiments with the labeled ketone of C. (=cinchonidinone) revealed its incorporation into the Cinchona alkaloids, especially in non-methoxylated members such as C. and cinchonine. For enzymatic studies, see. Lit., for synthetic investigations, see Lit.. The uses of C. are similar to those of quinine. 

Several factors are known to enhance the formation of thromboxanes, although their site of action may not necessarily be the enzyme, thromboxane synthetase. Some of these factors may be involved in the regulation of thromboxane biosynthesis in vivo. Thus, they may be of importance for the development of certain diseases a number of pathological conditions are known that seem to involve an increase in the thromboxane production by platelets or other cell types. These will be covered more in detail below (see section on Thromboxane production in pathological conditions). 

The final step of heme synthesis is catalyzed by ferrochelatase. This enzyme is firmly bound to the inner mitochondrial membrane (Jones and Jones, 1968). Incorporation of iron into protoporphyrin ring systems supplies heme for the electron transport system in cytochromes and for oxygen transport and storage in hemoglobin and myoglobin, respectively. Increased heme biosynthesis in vivo may stimulate mitochondrial cytochrome formation (Beattie, 1971). 

The relevance of these studies of the partially purified enzjrme to the regulation of purine biosynthesis in vivo is uncertain. 

BcsQ which is required for cellulose biosynthesis in vivo, is part of the cellulose biosynthesis operon in Enterobacteriaceae and G. xylinus. BcsC contains a N-terminal membrane domain and several tetratrico peptide repeats (TRPs) motifs, indicating that it might participate in protein-protein interactions. 

Most workers in the field agree that KOR probably has an indirect role in cellulose biosynthesis in vivo, but so far it has not been possible to assign a specific role to this protein in this process. In simple terms, it is believed that KOR hydrolyzes... 

Biosynthesis in vivo (in Uving cdls) via biosynthetic pathways, e.g. naturally occurring reactions in all living systems. 

The whole problem of DNA biosynthesis in vivo and in vitro is one of considerable extent and complexity and we have dealt with it here only in a very general manner. We shall not examine many aspects of this problem both because they have no direct bearing on the purpose of this book and also because the excellent surveys and monographs published every year (Tikhonenko, 1965 Vol -kenshtein, 1970 Ingram, 1965 Zbarskii and Debov, 1967) make a more comprehensive study of the problem of DNA synthesis superfluous in this book. 

It is concluded that in chloroplasts the carotenogenic enzymes apparently have a drastically altered activity and topology when compared with yellow or greening plastid types. Although chlorophyll and carotenoid biosynthesis in vivo proceeds in a sort of concerted action in chloroplasts, carotenogenic enzymes can not be detected in vitro in these organelles, whereas... 

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