Matrix pathways

Figure 5.6. The production of NPs using matrix pathways was predicted by Jones and Firn because of the opportunity to produce and retain chemical diversity efficiently. In this diagrammatic scheme, three enzymes (ei, e2 and es) have access to one substrate. The upper panel shows that if each of the enzymes has a strict substrate specificity, a linear pathway producing three new chemicals would be expected, ffowever, if the three enzymes have a broad substrate specificity then the order of conversion can vary and a matrix pathway will result. Now three enzymes will produce 11 novel substances. Furthermore, such matrix pathways are more robust to the loss of any one enzyme activity (see Figure 5.4).

Figure 5.7. There are many examples now known of the synthesis of NPs via matrix pathways (see also Figure 9.3). However, a nice example of the benefit of such flexibility was revealed when a mutant of spearmint that had smelled more like peppermint was studied.A comparison of the terpenes in both plants revealed that the single gene mutation had not resulted in a single chemical change but multiple changes, in the mutant plant, a hydroxyl group was added to the 3-position of the cyclohexene ring of limonene while the wild-type hydroxylated the 6-position. Some of the other wild-type tailoring enzymes in the mutant did not discriminate fully between the 3- and 6-hydroxylated products so a new family of NPs were produced which gave the mutant plant an odour of peppermint.

Tables VI and VII ). On the other hand, capric acid and decylmethyl sulfoxide showed a dual effect on the hydrophilic protein gel and also on the lipophilic fatty matrix. In the case of capric acid, the overall enhancement in the permeation of progesterone was increased by 354%, in which the protein gel pathway and fatty matrix pathway contribute approximately equally (with enhancement factor of 15.3 vs. 13.0). In the case of decylmethyl sulfoxide, the overall enhancement was improved by 515% (40.2 vs. 7.8).

Compared with the relatively unobstructed path for the diffusion of solvents in the atmosphere, diffusion coefficients for solvents in soil air will be less because of the tortuosity of the soil matrix pathways. Several functional relationships have been developed that relate the soil diffusion coefficient (DJ to various soil properties (see Roy and Griffin ), such as the Millington Equation ... 

Epithelial Polarity Proteins Regulate DrosophUa Tracheal Tube Size in Parallel to the Luminal Matrix Pathway. Curr Biol, VoL 20, pp.55-61. 

Laprise, P., Paul, S., Boulanger, J., Robbins, R., Beitel, G. J. Tepass, U. (2010). Epithelial polarity proteins regulate Drosophila tracheal tube size in parallel to the luminal matrix pathway. Current Biology 20, 55-61. 

The traditional way to provide the nuclear coordinates to a quantum mechanical program is via a Z-matrix, in which the positions of the nuclei are defined in terms of a set of intei ii.il coordinates (see Section 1.2). Some programs also accept coordinates in Cartesian formal, which can be more convenient for large systems. It can sometimes be important to choow an appropriate set of internal coordinates, especially when locating rninima or transitinn points or when following reaction pathways. This is discussed in more detail in Section 5.7. 

Figure 8 Effects of spin diffusion. The NOE between two protons (indicated by the solid line) may be altered by the presence of alternative pathways for the magnetization (dashed lines). The size of the NOE can be calculated for a structure from the experimental mixing time, and the complete relaxation matrix, (Ry), which is a function of all mterproton distances d j and functions describing the motion of the protons, y is the gyromagnetic ratio of the proton, ti is the Planck constant, t is the rotational correlation time, and O) is the Larmor frequency of the proton m the magnetic field. The expression for (Rjj) is an approximation assuming an internally rigid molecule.

The preparation of a matrix and the subsequent evaluation of the hazards identified can lead to a qualitative judgment of process risk and to the identification of available pathways to reduce that risk. Software is available to assist in making and maintaining interactionlike matrices. One example is a database shell called CHEMPAT (AIChE, 1995). When CHEMPAT is customized by the user, a compatibility chart is produced based on user-supplied chemical information. 

FIGURE 21.17 The electron transfer pathway for cytochrome oxidase. Cytochrome c binds on the cytosolic side, transferring electrons through the copper and heme centers to reduce O9 on the matrix side of the membrane. 

Most of the NADH used in electron transport is produced in the mitochondrial matrix space, an appropriate site because NADH is oxidized by Complex I on the matrix side of the inner membrane. Furthermore, the inner mitochondrial membrane is impermeable to NADH. Recall, however, that NADH is produced in glycolysis by glyceraldehyde-3-P dehydrogenase in the cytosol. If this NADH were not oxidized to regenerate NAD, the glycolytic pathway would cease to function due to NAD limitation. Eukaryotic cells have a number of shuttle systems that harvest the electrons of cytosolic NADH for delivery to mitochondria without actually transporting NADH across the inner membrane (Figures 21.33 and 21.34). 

COMPARTMENTALIZED PYRUVATE CARBOXYLASE DEPENDS ON METABOLITE CONVERSION AND TRANSPORT The second interesting feature of pyruvate carboxylase is that it is found only in the matrix of the mitochondria. By contrast, the next enzyme in the gluconeogenic pathway, PEP carboxykinase, may be localized in the cytosol or in the mitochondria or both. For example, rabbit liver PEP carboxykinase is predominantly mitochondrial, whereas the rat liver enzyme is strictly cytosolic. In human liver, PEP carboxykinase is found both in the cytosol and in the mitochondria. Pyruvate is transported into the mitochondrial matrix, where it can be converted to acetyl-CoA (for use in the TCA cycle) and then to citrate (for fatty acid synthesis see Figure 25.1). /Uternatively, it may be converted directly to 0/ A by pyruvate carboxylase and used in glu-... 

All of the other enzymes of the /3-oxidation pathway are located in the mitochondrial matrix. Short-chain fatty acids, as already mentioned, are transported into the matrix as free acids and form the acyl-CoA derivatives there. However, long-chain fatty acyl-CoA derivatives cannot be transported into the matrix directly. These long-chain derivatives must first be converted to acylearnitine derivatives, as shown in Figure 24.9. Carnitine acyltransferase I, located on the outer side of the inner mitochondrial membrane, catalyzes the formation of... 

Fluorid ions stimulate bone formation by a direct mitogenic effect on osteoblasts mediated via protein kinase activation and other pathways. Further to these cellular effects, fluorides alter hydroxyapatite crystals in the bone matrix. In low doses, fluorides induce lamellar bone, while at higher doses abnormal woven bone with inferior quality is formed. The effect of fluorides on normal and abnormal (e.g. osteoporotic) bone therefore depends on the dose administered. 

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. 

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