Lysine biosynthetic pathways

The oomycetes, hyphochytrids, labyrinthuloids, and thraustochytrids are included in the kingdom Heterokontobionta or pseudofungi [54] based on the presence of cellulose in their cell walls, a tubular mitochondrial crista, hetero-kont flagella, one decorated with tripartite hairs, and the a, (3-diaminopimelic acid lysine biosynthetic pathway. The slime molds were classified into the kingdom Protozoa [38]. 

C. (2013) Increased lysine production by flux coupling of the tricarboxylic acid cycle and the lysine biosynthetic pathway - metabolic engineering of the availability of succinyl-CoA in Corynebacterium glutamicum. Metab. 

In fungi, although a-aminoadipaie is available fiom the lysine biosyniheTic pathway, it could also be obtained from a lysine catabolic pathway, similar to that fouiKl in the actinomycetes, and be channeled into penicillin biosynthesis. In keeping with this possibility, a lysine auxotroph of Pentdltium cfiryspgenum with a block before a-aminoadi-pate formation was found to produce penicillin in a lysine-supplemented medium, and it showed LAT activity (17). Therefore, in fungi, in addition to the lysine biosynthetic pathway, lysine catabolism may also provide a-aminoadipate for penicillin biosynthesis however, the relative contribution of each pathway is unclear. 

Figure 12.2 Lysine biosynthetic pathways. Six iysine biosynthetic pathways are discovered so far. a-amino adipate route (AAA) has two variants and Diaminopimeiate route (DAP) has four variants— Amino transferase pathway (Chlamydia), Succinyiase pathway (Gram-positive and Gram-negative bacteria), Acetyiase pathway (Bacillus), and Dehydrogenase pathway (Corynebacterium). in C. glutamicum succinyiase and dehydrogenase pathways are operated.

Velasco AM, Leguina Jl, Lazeano A. Molecular evolution of the lysine biosynthetic pathways./ Mol Ewl 2002 55 445-59. 

Methionine, threonine, lysine, isoleucine, valine, and leucine are essential amino acids. Their biosynthetic pathways are complex and interconnected (Fig. 22-15). 

Probably the most common and widespread control mechanisms in cells are allosteric inhibition and allosteric activation. These mechanisms are incorporated into metabolic pathways in many ways, the most frequent being feedback inhibition. This occurs when an end product of a metabolic sequence accumulates and turns off one or more enzymes needed for its own formation. It is often the first enzyme unique to the specific biosynthetic pathway for the product that is inhibited. When a cell makes two or more isoenzymes, only one of them may be inhibited by a particular product. For example, in Fig. 11-1 product P inhibits just one of the two isoenzymes that catalyzes conversion of A to B the other is controlled by an enzyme modification reaction. In bacteria such as E. coli, three isoenzymes, which are labeled I, II, and III in Fig. 11-3, convert aspartate to (3-aspartyl phosphate, the precursor to the end products threonine, isoleucine, methionine, and lysine. Each product inhibits only one of the isoenzymes as shown in the figure. 

An intermediate in Eq. 21-13 may be converted to 4-hydroxy-2-nonenal, a prominent product of the peroxidation of arachidonic or linoleic acids (Eq. 21-15).242 243a However, other biosynthetic pathways to this compound are possible.244 2443 4-Hydroxy-2-nonenal can react with side chains of lysine, cysteine, and histidine245 to form fluorescent products such as the following cyclic compound generated by an oxidative reaction.246... 

Eight enzyme-catalyzed reactions are involved in the conversion of acetyl-CoA into fatty acids. The first reaction is catalyzed by acetyl-CoA carboxylase and requires ATP. This is the reaction that supplies the energy that drives the biosynthesis of fatty acids. The properties of acetyl-CoA carboxylase are similar to those of pyruvate carboxylase, which is important in the gluconeogenesis pathway (see chapter 12). Both enzymes contain the coenzyme biotin covalently linked to a lysine residue of the protein via its e-amino group. In the last section of this chapter we show that the activity of acetyl-CoA carboxylase plays an important role in the control of fatty acid biosynthesis in animals. Regulation of the first enzyme in a biosynthetic pathway is a strategy widely used in metabolism. 

Figure 8.6 Cross-links in elastin involving desmosine and isodesmosine with suggested biosynthetic pathways. Both amino acids contain pyridinium rings, and both contain the elements of four allysine/lysine residues. (Reproduced by permission from Guay M, Lamy F. The troublesome cross-links of elastin 1979. Trends Biochem Sci July, 1979, p. 161.)...

Carnitine biosynthesis utilizes the essential amino acid lysine, with terminal methyl groups donated by S-adenosylmethionine. Only lysine incorporated into proteins is a substrate for the methylation reaction. In humans, the final reaction in the biosynthetic pathway, catalyzed by a cytosolic hydroxylase, occurs in liver and kidney but not in cardiac or skeletal muscle. The carnitine requirement of these tissues is met by carnitine transported to them via the plasma... 

The rather similar alkaloids anabasine and anatabine come from different biosynthetic pathways. Labelling experiments outlined below show the origin of one carbon atom from lysine and others from nicotinic acid. Suggest detailed pathways. (Hint. Nicotinic acid and the intermediate yoi have been using in Problem 3 in the biosynthesis of the piperidine alkaloid are both electrophilic at position 2. You also need an intermediate derived from nicotinic acid which is nucleophilic at position 3. The biosynthesis involves reduction.)... 

The L-threonine biosynthetic pathway consists of five enzymatic steps from L-aspartate. E. coli has three aspartate kinase isoenzymes, key enzymes which catalyze the first reaction of the L-threonine biosynthetic pathway. The aspartate kinase isoenzymes I, II, and III encoded by the thrA, metL, and lysC genes, respectively, are affected by feedback inhibition by L-threonine, L-methionine, and L-lysine, respectively. C. glutamicum has only one aspartate kinase encoded by the lysC gene, which is subjected to feedback inhibition by L-lysine and... 

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