Figure 3. The methionine/SAMe cycle is required for the protective effects of vitamin B₁₂.

(A) Diagram of vitamin-B₁₂-dependent pathways in C. elegans. Genes encoding enzymes that function in the methionine/SAMe cycle (blue) and the canonical B₁₂ pathway (red) are indicated. SAMe, S-adenosylmethionine; SAH, s-adenosyl-l-homocysteine.

(B) pcca-1(ok2282) had no effect on the diet-induced shift in paralysis of Aβ animals (n ≥ 57).

(C) Loss of mmcm-1(ok1637) did not eliminate the dietary shift (n ≥ 67).

(D) metr-1(ok521) accelerated Aβ-induced paralysis and eliminated the impact of E. coli diet (n ≥ 60).

(E) In metr-1 mutant Aβ animals, ATP levels were low and unaffected by diet (n ≥ 7).

(F) H₂O₂ levels were unaffected by diet in metr-1 mutant Aβ animals (n = 4).

(G) O₂⁻ levels were unaffected by diet in metr-1 mutant Aβ animals (n ≥ 6).

(H) sams-1(ok2946) delayed Aβ-induced paralysis and eliminated the dietary shift (n ≥ 26).

Error bars show SEM; *p < 0.05 and ***p < 0.001, one-way ANOVA with Dunnett’s post-test. See also Figure S4.