Principles of Biochemistry Volume 2 - A. Lehninger 1985

Bioenergetics and Metabolism
Biosynthesis of Amino Acids and Nucleotides
Cysteine is synthesized from two other amino acids: methionine and serine

In mammals, Cysteine is synthesized from the essential amino acid Methionine and the non-essential amino acid Serine. Methionine provides the sulfur atom for cysteine synthesis, while serine supplies the carbon Skeleton. In the first reaction of this biosynthetic pathway, methionine reacts with ATP to form S-adenosylmethionine (Fig. 22-4)

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The adenosyl group can be viewed as a carrier for the methionine molecule. In this form, the methyl group of methionine is highly reactive and can be transferred to any of various methyl group acceptors, leaving behind the demethylated product S-adenosylhomocysteine

S-Adenosylmethionine + Methyl group acceptor →

→ S-Adenosylhomocysteine +

+ Methylated acceptor.

Fig. 22-4. Structure of S-adenosylmethionine. In this derivative of methionine, the stable sulfur atom involved in the thioether bond becomes highly reactive and can readily transfer its methyl group to various acceptors.

As we have already seen (Section 21.12), S-adenosylmethionine serves as a methyl group donor during The conversion of phosphatidylethanolamine to phosphatidylcholine.

Following the removal of the methyl group, S-adenosylhomocysteine undergoes further transformations that ultimately yield cysteine (Fig. 22-5). The next step produces free homocysteine

S-Adenosylhomocysteine + Н₂О →

→ Adenosine + Homocysteine.

Fig. 22-5. Biosynthesis of cysteine from methionine and serine. Methionine provides the sulfur atom for this synthesis, and serine provides the carbon skeleton.

Homocysteine then reacts with serine in a reaction catalyzed by cystathionine β-synthase, leading to The formation of cystathionine (Fig. 22-5)

Homocysteine + Serine →

→ Cystathionine + Н₂О.

In the final step, cystathionine γ-lyase—another enzyme that utilizes Pyridoxal phosphate as a prosthetic group—catalyzes the removal of ammonia and the Cleavage of cystathionine to yield free cysteine (Fig. 22-5)

Cystathionine + Н⁺→

→ а-Ketobutyrate + NH⁺₄ + Cysteine.

Combining all these individual steps gives the overall equation for cysteine synthesis

L-Methionine + ATP + Methyl group acceptor + Н₂О + Н⁺ +

+ Serine → Methylated acceptor + Adenosine +

+ а-Ketobutyrate +

+ NH⁺₄ + Cysteine 4 PP_i + P_i. The net result of this complex sequence of reactions is the replacement of the serine OH group with the SH group derived from methionine, thereby forming cysteine (Fig. 22-5).