Protein metabolic pathway

Schmidt-Dannert C. Directed evolution of single proteins, metabolic pathways, and viruses. Biochemistry 2001 40 13125-13136. 

KEGG http //ww w. genome, j p/kegg Integrated DB on genes, proteins, metabolic pathways... 

Template recognition is the process of finding the most similar sequence. The researcher must choose how to compute similarity. It is possible to run a fast, approximate search of many sequences or a slow, accurate search of a few sequences. Sequences that should be analyzed more carefully are the same protein from a different species, proteins with a similar function or from the same metabolic pathway, or a library of commonly observed substructures if available. 

The World Wide Web has transformed the way in which we obtain and analyze published information on proteins. What only a few years ago would take days or weeks and require the use of expensive computer workstations can now be achieved in a few minutes or hours using personal computers, both PCs and Macintosh, connected to the internet. The Web contains hundreds of sites of Interest to molecular biologists, many of which are listed in Pedro s BioMolecular Research Tools (http // www.fmi.ch/biology/research tools.html). Many sites provide free access to databases that make it very easy to obtain information on structurally related proteins, the amino acid sequences of homologous proteins, relevant literature references, medical information and metabolic pathways. This development has opened up new opportunities for even non-specialists to view and manipulate a structure of interest or to carry out amino-acid sequence comparisons, and one can now rapidly obtain an overview of a particular area of molecular biology. We shall here describe some Web sites that are of interest from a structural point of view. Updated links to these sites can be found in the Introduction to Protein Structure Web site (http // WWW.ProteinStructure.com/). 

Although the interior of a prokaryotic cell is not subdivided into compartments by internal membranes, the cell still shows some segregation of metabolism. For example, certain metabolic pathways, such as phospholipid synthesis and oxidative phosphorylation, are localized in the plasma membrane. Also, protein biosynthesis is carried out on ribosomes. 

The use of foods by organisms is termed nutrition. The ability of an organism to use a particular food material depends upon its chemical composition and upon the metabolic pathways available to the organism. In addition to essential fiber, food includes the macronutrients—protein, carbohydrate, and lipid—and the micronutrients—including vitamins and minerals. 

We ll see later in this chapter and again in Chapter 29 that carbonyl condensation reactions occur frequently in metabolic pathways. In fact, almost all classes of biomolecules—carbohydrates, lipids, proteins, nucleic acids, and many others—are biosynthesized through pathways that involve carbonyl condensation reactions. As with the or-substitution reaction discussed in the previous chapter, the great value of carbonyl condensations is that they are one of the few general methods for forming carbon-carbon bonds, thereby making it possible to build larger molecules from smaller precursors. We ll see how and why these reactions occur in this chapter. 

Biochemistry is carbonyl chemistiy. Almost all metabolic pathways used by living organisms involve one or more of the four fundamental carbonvl-group reactions we ve seen in Chapters 19 through 23. The digestion and metabolic breakdown of all the major classes of food molecules—fats, carbohydrates, and proteins—take place by nucleophilic addition reactions, nucleophilic acyl substitutions, a substitutions, and carbonyl condensations. Similarly, hormones and other crucial biological molecules are built up from smaller precursors by these same carbonyl-group reactions. 

Biological raw data are stored in public databanks (such as Genbank or EMBL for primary DNA sequences). The data can be submitted and accessed via the World Wide Web. Protein sequence databanks like trEMBL provide the most likely translation of all coding sequences in the EMBL databank. Sequence data are prominent, but also other data are stored, e.g.yeast two-hybrid screens, expression arrays, systematic gene-knock-out experiments, and metabolic pathways. 

Histidine phosphatases and aspartate phosphatases are well established in lower organisms, mainly in bacteria and in context with two-component-systems . Reversible phosphorylation of histidine residues in vertebrates is in its infancy. The first protein histidine phosphatase (PHP) from mammalian origin was identified just recently. The soluble 14 kD protein does not resemble any of the other phosphatases. ATP-citrate lyase and the (3-subunit of heterotrimeric GTP-binding proteins are substrates of PHP thus touching both, metabolic pathways and signal transduction [4]. 

Fatal hereditary disorder that typically presents in the neonatal period. Clinical features include an array of hepatic, renal and neurological dysfunctions. Patients with Zellweger syndrome rarely survive the first year of life. The disease is caused by mutations in the Pex proteins leading to an defective import of peroxisomal matrix proteins and consequently to a loss of most peroxisomal metabolic pathways. 

To correlate embryonic arrests with the metabolic pathways, and especially to understand why cellular organelles first undergo chemical damages, biological investigations include evaluation of DNA, RNA, protein, glucose, lipid, and adenosine-5 -triphosphate (ATP) contents, whose fractions are extracted and isolated by modified Schneider methods. In particular,... 

Plants are constantly subject to adverse environmental conditions such as drought, flooding, extreme temperatures, excessive salts, heavy metals, high-intensity irradiation and infection by pathogenic agents. Because of their immobility, plants have to make necessary metabolic and structural adjustments to cope with the stress conditions. To this end, the expression of the genetic programme in plants is altered by the stress stimuli to induce and/or suppress the production of specific proteins which are either structural proteins or enzymes for specific metabolic pathways. 

Glycine is the simplest of all amino acids. It is involved in many metabolic pathways, is an essential component of proteins, and is found throughout the brain. A neurotransmitter role for glycine was first identified in the spinal cord, where it was found to be differentially distributed between dorsal and ventral regions and shown to cause hyperpolarisation of motoneurons (Werman et al. 1967). This inhibitory action of glycine is distinct from its... 

Whatever the true details of the metabolic pathway shown in Scheme 1 might be, there are certain facts which are very secure. Among these are that the nitrosamines are oxidatively dealkylated, that electrophilic intermediates which alkylate proteins and nucleic acids are formed, and that one of the... 

FIGURE 3.2.2 Metabolic pathways of carotenoids such as p-carotene. CM = chylomicrons. VLDL = very low-density lipoproteins. LDL = low-density lipoproteins. HDL = high-density lipoproteins. BCO = p-carotene 15,15 -oxygenase. BCO2 = p-carotene 9, 10 -oxygenase. LPL = lipoprotein lipase. RBP = retinol binding protein. SR-BI = scavenger receptor class B, type I. 

Insulin also plays a role in fat metabolism. In humans, most fatty acid synthesis takes place in the liver. The mechanism of action of insulin involves directing excess nutrient molecules toward metabolic pathways leading to fat synthesis. These fatty acids are then transported to storage sites, predominantly adipose tissue. Finally, insulin stimulates the uptake of amino acids into cells where they are incorporated into proteins. 

Conventionally, central and special metabolic pathways are distinguished. Central pathways are common to the decomposition and synthesis of major macromolecules. Actually, they are much alike in all representatives of the living world. Special cycles are characteristic of the synthesis and decomposition of individual monomers, macromolecules, cofactors, etc. Special cycles are extremely diversified, especially in the plant kingdom. For this reason, the plant metabolism is conventionally classified into primary and secondary metabolisms. The primary metabolism includes the classical processes of synthesis and deeradation of major macromolecules (proteins, carbohydrates, lipids, nucleic acids, etc.), while the secondary metabolism ensuing from the primary one includes the conversions of special biomolecules (for example, alkaloids, terpenes, etc.) that perform regulatory or other functions, or simply are metabolic end byproducts. 

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