Biochemistry - The Chemical Reactions of Living Cells, Volume 3 - D. Metzler 1980

Metabolism of Nitrogenous Compounds
Compounds Derived from Aspartate
Lysine, Diaminopimelate, Dipicolinic Acid, and Carnitine

Although animals are generally unable to synthesize Lysine and consider it one of the Essential Amino Acids that must be obtained through diet, two distinct pathways for its production are known in other organisms. The $\alpha$-aminoadipate pathway (Fig. 14-2) is found only in certain lower Fungi, higher fungi, and euglenoids. The starting material is the 5-carbon $\alpha$-ketoglutarate. Bacteria, other species of lower fungi, and green plants utilize the diaminopimelate pathway (Fig. 14-7), which begins with the 4-carbon aspartate.

The $\alpha$-aminoadipate pathway (Fig. 14-2) runs parallel to the Ornithine Biosynthesis pathway. It involves the chain elongation of $\alpha$-ketoglutarate (Fig. 11-7), converting it into $\alpha$-ketoadipate, which is then transformed into $\alpha$-aminoadipate via Transamination. This is followed by an ATP-dependent reduction to the aldehyde. The final transamination step proceeds in an unusual manner, without the participation of a PLP-dependent enzyme: the aldehyde forms a Schiff base with glutamate, followed by reduction to saccharopine. This is succeeded by an oxidation step, yielding a Schiff base between lysine and ketoglutarate.

Class="center">

FIG. 14-7. Biosynthesis of lysine via the diaminopimelate pathway.

During the diaminopimelate pathway of lysine synthesis (Fig. 14-7), aspartate is converted into aspartate semialdehyde, to which an additional 2-carbon unit is added via an aldol Condensation with Pyruvate. Decarboxylation at The final stage leads to The formation of lysine. A number of cyclic intermediates arise along this pathway, although It is worth noting that the initial aldol condensation product (enclosed in parentheses in Fig. 14-7) is converted to diaminopimelic acid through a simple reaction sequence involving $\alpha,\beta$-elimination of the hydroxyl group, NADPH-dependent reduction, and transamination. The process is complicated by an inherent tendency toward ring closure. A succinylation step (Fig. 14-7) is required precisely to shift the equilibrium back toward open-chain compounds. This pathway is of particular importance for prokaryotic organisms because it yields dipicolinic acid—vital to them—as a byproduct, while diaminopimelic acids are formed at intermediate stages. Cyclic dipicolinic acid is an essential component of bacterial spores and is rarely found anywhere else in nature. L,L- and meso-diaminopimelic acids are Key Components of Introduction/37.html">Bacterial Cell wall peptidoglycans (Chap. 5, Sec. D).

In addition to being incorporated into Proteins, lysine can also undergo methylation followed by degradation to $\gamma$-butyrobetaine [49, 50].

This compound is formed as an intermediate during carnitine biosynthesis [50a]: