Processes

Transsulfuration Pathway

Metabolic pathway converting homocysteine to cysteine via cystathionine; requires B6; irreversible.

The transsulfuration pathway is an irreversible metabolic route that converts homocysteine to cysteine, diverting sulfur from the methionine cycle toward glutathione and taurine synthesis. The pathway consists of two B6-dependent reactions: CBS (cystathionine beta-synthase) combines homocysteine with serine to form cystathionine, then CSE (cystathionine gamma-lyase) cleaves cystathionine to produce cysteine plus alpha-ketobutyrate and ammonia.

This pathway is the only way mammals can synthesize cysteine from methionine. Transsulfuration activity increases when methionine/SAMe levels are high (CBS is activated by SAMe), directing excess sulfur amino acids toward disposal while producing the antioxidant precursor cysteine.

B6 deficiency impairs both enzymes, trapping homocysteine.

Metabolic Connections

Transsulfuration Pathway connects to 9 other pathways.

B Vitamins

B6

Both enzymes of transsulfuration (CBS, CSE) require B6 as cofactor

Pyridoxine - essential for over 100 enzyme reactions including neurotransmitter synthesis and transsulfuration.

B6

B6 is essential for both enzymes of transsulfuration (CBS and CSE)

Pyridoxine - essential for over 100 enzyme reactions including neurotransmitter synthesis and transsulfuration.

Detoxification

CBS

CBS catalyzes the first step of transsulfuration

Cystathionine beta-synthase - enzyme directing homocysteine toward glutathione production via the transsulfuration pathway.

Glutathione

Transsulfuration provides cysteine for glutathione synthesis

Master antioxidant and detoxifier. Tripeptide of glutamate, cysteine, and glycine essential for cellular protection.

Enzymes

CSE (Cystathionine Gamma-Lyase)

CSE catalyzes the second step of transsulfuration

Enzyme that cleaves cystathionine to produce cysteine; B6 dependent; also produces hydrogen sulfide.

Metabolites

Cystathionine

Cystathionine is the intermediate of transsulfuration

Intermediate in transsulfuration pathway; formed from homocysteine and serine by CBS enzyme.

Amino Acids

Cysteine

Cysteine is the end product of transsulfuration

Sulfur-containing amino acid - rate-limiting precursor for glutathione synthesis.

Methylation

Homocysteine

Transsulfuration consumes homocysteine, removing it from the methylation cycle

Sulfur-containing amino acid at the crossroads of methylation. Elevated levels indicate impaired methylation or B-vitamin deficiency.

SAMe

SAMe activates CBS, increasing transsulfuration when methylation is adequate

S-Adenosylmethionine - universal methyl donor essential for 200+ methylation reactions including neurotransmitter synthesis and DNA methylation.