Cysteine, a sulfur-containing amino acid, can be desulfurized to produce pyruvate. The resulting sulfate can be utilized to synthesize 3′phosphoadenosine-5′-phosphosulfate (PAPS), which acts as an activated sulfate donor to various acceptors. Cysteine can also be oxidized to form cystine, its disulfide derivative.

Threonine, although it is converted to pyruvate in most organisms, is a minor pathway in humans.

Phenylalanine can undergo hydroxylation to generate tyrosine, which is an irreversible reaction catalyzed by phenylalanine hydroxylase (PAH), requiring tetrahydrobiopterin. This reaction initiates the breakdown of phenylalanine. Consequently, the pathways of phenylalanine metabolism and tyrosine metabolism merge, leading to the formation of fumarate and acetoacetate. Hence, both phenylalanine and tyrosine are considered glucogenic and ketogenic.

Inherited deficiencies in the enzymes involved in phenylalanine and tyrosine metabolism result in diseases such as phenylketonuria (PKU), tyrosinemia, alkaptonuria, and albinism.

Methionine, one of the amino acids that form succinyl CoA, is a sulfur-containing amino acid with significant importance. It is converted to S-adenosylmethionine (SAM), which serves as the primary methyl group donor in one-carbon metabolism. Methionine is also responsible for the production of homocysteine (Hcy), a metabolite associated with atherosclerotic vascular disease and thrombosis.

SAM synthesis involves the condensation of methionine and ATP, resulting in the formation of SAM, a high-energy compound that lacks phosphate. The hydrolysis of all three phosphate bonds in ATP drives the formation of SAM.

The methyl group attached to the sulfur in SAM is activated and can be transferred by methyltransferases to various acceptors, such as norepinephrine in the synthesis of epinephrine. Methyl transfer usually occurs to nitrogen or oxygen atoms, although it can also occur to carbon atoms. The transfer of the methyl group is typically irreversible due to the resulting loss of free energy. The reaction product, S-adenosylhomocysteine (SAH), is a thioether similar to methionine.

Following the donation of the methyl group, SAH undergoes hydrolysis to produce Hcy and adenosine. Hcy can follow two pathways depending on the availability of methionine. In cases of methionine deficiency, Hcy can be remethylated to form methionine. However, if methionine stores are sufficient, Hcy can enter the transsulfuration pathway, where it is converted to cysteine.
Cysteine: This sulfur-containing amino acid undergoes desulfurization to yield pyruvate. [Note: The sulfate released can be used to synthesize 3′phosphoadenosine-5′-phosphosulfate (PAPS), an activated sulfate donor to a variety of acceptors.] Cysteine can also be oxidized to its disulfide derivative, cystine.
5.
Threonine: This amino acid is converted to pyruvate in most organisms but is a minor pathway (at best) in humans.
D. Amino acids that form fumarate 1.
Phenylalanine and tyrosine: Hydroxylation of phenylalanine produces tyrosine (Fig. 20.7). This irreversible reaction, catalyzed by tetrahydrobiopterin-requiring phenylalanine hydroxylase (PAH), initiates the catabolism of phenylalanine. Thus, phenylalanine metabolism and tyrosine metabolism merge, leading ultimately to fumarate and acetoacetate formation. Therefore, phenylalanine and tyrosine are both glucogenic and ketogenic.
2.
Inherited deficiencies: Inherited deficiencies in the enzymes of phenylalanine and tyrosine metabolism lead to the diseases phenylketonuria (PKU) (see p. 270), tyrosinemia (see p. 274), and alkaptonuria (see p. 274) as well as the condition of albinism (see p. 273).
E. Amino acids that form succinyl CoA: Methionine
Methionine is one of four amino acids that form succinyl CoA. This sulfur-containing amino acid deserves special attention because it is converted to S-adenosylmethionine (SAM), the major methyl group donor in one-carbon metabolism (Fig. 20.8). Methionine is also the source of homocysteine (Hcy), a metabolite associated with atherosclerotic vascular disease and thrombosis (see p. 265).
the methyl group carrier and donor.] PPi = pyrophosphate; Pi = inorganic phosphate; NH3 = ammonia.
1.
S-Adenosylmethionine synthesis: Methionine condenses with ATP, forming SAM, a high-energy compound that is unusual in that it contains no phosphate. The formation of SAM is driven by hydrolysis of all three phosphate bonds in ATP (see Fig. 20.8).
2.
Activated methyl group: The methyl group attached to the sulfur in SAM is activated and can be transferred by methyltransferases to a variety of acceptors such as norepinephrine in the synthesis of epinephrine. The methyl group is usually transferred to nitrogen or oxygen atoms (as with epinephrine synthesis and degradation, respectively; see p. 286) and sometimes to carbon atoms (as with cytosine). The reaction product, Sadenosylhomocysteine (SAH), is a simple thioether, analogous to methionine. The resulting loss of free energy makes methyl transfer essentially irreversible.
3.
S-Adenosylhomocysteine hydrolysis: After donation of the methyl group, SAH is hydrolyzed to Hcy and adenosine. Hcy has two fates. If there is a deficiency of methionine, Hcy may be remethylated to methionine (see Fig. 20.8). If methionine stores are adequate, Hcy may enter the transsulfuration pathway, where it is converted to cysteine.