Methyl groups cycle

Fig. 1. The choline and methionine cycles showing the origin and disposition of labile methyl groups. FAH = tetrahydrofolic acid CH3BJ2 = methylated...

When these labeled oxaloacetates enter a second turn of the cycle, both of the carboxyl carbons are lost as CO2, but the methylene and carbonyl carbons survive through the second turn. Thus, the methyl carbon of a labeled acetyl-CoA survives two full turns of the cycle. In the third turn of the cycle, one-half of the carbon from the original methyl group of acetyl-CoA has become one of the carboxyl carbons of oxaloacetate and is thus lost as CO2. In the fourth turn of the cycle, further scrambling results in loss of half of the remaining labeled carbon (one-fourth of the original methyl carbon label of acetyl-CoA), and so on. 

Although /3-oxidation is universally important, there are some instances in which it cannot operate effectively. For example, branched-chain fatty acids with alkyl branches at odd-numbered carbons are not effective substrates for /3-oxidation. For such species, a-oxidation is a useful alternative. Consider phy-tol, a breakdown product of chlorophyll that occurs in the fat of ruminant animals such as sheep and cows and also in dairy products. Ruminants oxidize phytol to phytanic acid, and digestion of phytanic acid in dairy products is thus an important dietary consideration for humans. The methyl group at C-3 will block /3-oxidation, but, as shown in Figure 24.26, phytanic acid a-hydroxylase places an —OFI group at the a-carbon, and phytanic acid a-oxidase decar-boxylates it to yield pristanie add. The CoA ester of this metabolite can undergo /3-oxidation in the normal manner. The terminal product, isobutyryl-CoA, can be sent into the TCA cycle by conversion to succinyl-CoA. 

Fig. 2.2 A. Chemical structure of the three types of lignin monomer units H, p-hydroxyphenyl- G, guaiacyl and S, syringyl. Note the methyl groups (boxed) in the methoxy moieties of the G and S monomers. B. Pie chart showing the proportions of pine xylem ESTs that putatively encode enzymes of Ci metabolism, glycolysis, and the TCA cycle.

The best characterized B 12-dependent methyltransferases is methionine synthase (Figure 15.11) from E. coli, which catalyses the transfer of a methyl group from methyltetrahydrofolate to homocysteine to form methionine and tetrahydrofolate. During the catalytic cycle, B12 cycles between CH3-Co(in) and Co(I). However, from time to time, Co(I) undergoes oxidative inactivation to Co(II), which requires reductive activation. During this process, the methyl donor is S-adenosylmethionine (AdoMet) and the electron donor is flavodoxin (Fid) in E. coli, or methionine synthase reductase (MSR) in humans. Methionine synthase... 

Fig. 8.3 Dimethylsulfoniopropionate and dimethyl sulfide cycling in the open ocean. DMSO dimethylsulfoxide, CCN cloud condensation nuclei, MMPA 3-methylpropionate, ji-HP (S-hydrox-ypropionate, 3-MPA 3-mercaptopropionate, MeSH methanethiol, X-CH unidentified molecule with a terminal methyl group. (Reprinted from Yoch 2002, with permission from D. Yoch and the American Society for Microbiology)...

The methyl group for aU these reactions is obtained primarily from the degradation of the amino acid serine as it is converted to glycine. This sequence of reactions is sometimes known as the folic acid or tetra-hydrofolate cycle (Figure 15.6). 

The names of mono- or divalent cyclic substituents are formed by adding the suffix -yl or -ylidene, as appropriate, to the name of the cycle, with the exception of cycloalkanes, for which the suffixes replace the ending -ane rather than adding to it. Note that designations such as >— and C— are used to indicate a free valence whenever >— and C— might otherwise be taken to indicate an appended methyl group. 

The (Wcycie + m — )RT/2 term of Eq. (9.10) accounts for the fact that internal rotations are hindered in cychc structures [44,180] it was found that an amount of jRT should be subtracted from ZPE + 7/j- Hq for each of the (Wcycie + m 1) carbon-carbon bonds making up the cycle(s). A test carried out for -trans-2-cis-3-trimethylcyclohexane does not suggest that the rotation of the methyl group on C-2 is hindered, according to the present results. 

Transfer of the methyl group from 5,-adenosylmethi-onine to an acceptor yields S -adenosylhomocysteine (Fig. 18-18, step (2)), which is subsequently broken down to homocysteine and adenosine (step (3)). Methionine is regenerated by transfer of a methyl group to homocysteine in a reaction catalyzed by methionine synthase (step (4)), and methionine is reconverted to 5-adenosyl-methionine to complete an activated-methyl cycle. 

The carbon skeletons of methionine, isoleucine, threonine, and valine are degraded by pathways that yield suc-cinyl-CoA (Fig. 18-27), an intermediate of the citric acid cycle. Methionine donates its methyl group to one of several possible acceptors through S-adenosytmethionine,... 

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