Metabolism of Sulfur-Containing Amino Acids

Inorganic sulfur in the environment (primarily sulfate, but also sulfur, and sulfite) must undergo fixation to be ulitized by organisms. The fixation of sulfate is largely confined to plants and bacteria. Fixation begins with the formation of PAPS (3'-phosphoadenosine-5'-phosphosulfate) (see here). PAPS is formed in a two-step reaction from sulfate ion and two molecules of ATP (see here).

PAPS is an activated sulfate compound and is an intermediate in all organisms for sulfate esterification, such as the synthesis of chondroitin sulfate.

In bacteria PAPS is a substrate for sulfate reduction. In plants, adenosine-5'-phosphosulfate is the substrate. Thioredoxin, a small thiol-containing protein, reduces the sulfate in PAPS to sulfite (SO 32-). Sulfite is reduced by sulfite reductase in a six electron transfer through the intermediates NADPH, FAD, FMN, an iron-sulfur center, and the porphyrin siroheme. The end product is H 2S.

Bacteria and Plants - Bacteria and plants use H 2 S to synthesize cysteine, which is then metabolized to make methionine (Figure 21.5, Figure 21.6).

Some bacteria link serine to H 2S (see here) to make cysteine (Cys). However, plants and most bacteria react -O-acetylserine with H 2 S to make cysteine, as shown here.

Animals - Mammals require methionine (Met) in their diets (i.e., Met is an essential amino acid) and Cys can be made from Met, as shown in Figure 21.7. Thus, Cys is nonessential as long as sufficient Met is present in the diet. Mammals make Met from homocysteine, as shown in the reaction here. Figure 21.8 shows the pathway from Met to Cys and reveals that it is quite similar to the reverse of the methionine synthesis pathway in bacteria shown in Figure 21.5. Plants and bacteria also use the pathway shown in Figure 21.8 so they can synthesize one from the other, depending on their immediate needs. Methionine can also be made by conversion of choline, as shown here.

Cystathionine (made by cystathionine synthase from homocysteine and serine) plays a central role both in the biosynthesis of methionine in plants and bacteria and in the biosynthesis of cysteine in animals. In humans, deficiency of cystathionine synthase leads to a condition called homocystinuria, in which homocysteine overaccumulates. The condition results in severe mental retardation and dislocation of the lens of the eye.

The principal catabolic pathways for Cys and Met are outlined in Figure 21.11.

See also: Metabolism of Glutathione, S-Adenosylmethionine and Biological Methylation

INTERNET LINKS:

> 1. Sulfur Metabolism

> 2. Methionine Metabolism

> 3. Cysteine Metabolism