Effect of garlic on blood pressure via the hydrogen sulfide (H2S) pathway, and influence of dietary and genetic factors on homocysteine levels.
Notes: Blue rectangles illustrate metabolites, blue circles represent enzymes, orange circles are dietary cofactors, green star shapes show garlic and other polysulfide-containing nutrients, red rectangle indicates H2S, and purple rectangles represent direct and indirect influence of H2S on vasodilation and blood pressure. Red circles 1–7: Influence of dietary and genetic factors on H2S pathway 1= genetic polymorphism, homozygous for deleterious allele, leads to impaired folate metabolism. 2= common polymorphisms, some of which lead to increased homocysteine and decreased methylation and SAM levels; these respond well to folate supplementation. 3= genetic defects lead to increased homocysteine levels. 4= low Vit B12 levels lead to increased homocysteine levels. 5= defect in CBS enzyme leads to increased homocysteine levels and reduced H2S production. 6= low Vit B6* levels may increase homocysteine levels and reduce H2S production, and may respond to Vit B6 supplementation. 7= dietary intake of garlic polysulfides and thiosulfides can increase H2S nonenzymatically, and may ameliorate genetic defects in the CBS enzyme, or dietary deficiencies in Vit B6 and/or the sulfur-containing amino acids cysteine and methionine.
Abbreviations: CAT, cysteine-amino-transferase; CBS, cystathionine-β-synthase; CSE, cystathionine-γ-lyase; CysSSCys, oxidized cysteine/cystine; eNOS, endothelial nitric oxide synthase; Glu, L-glutamic acid; Gly, glycine; GSSG, oxidized glutathione; GSH, reduced glutathione; H2O2, hydrogen peroxide; K+, potassium ion; MPST, mercapto pyruvate sulfur transferase; NADPH, nicotinamide adenine dinucleotide phosphate; MTHFR, methylene-tetra-hydro-folate reductase; SAH, S-adenosyl-homocysteine; SAM, S-adenosyl-methionine; Se, selenium; Vit B6*, activated form of Vit B6 = pyridoxal-phosphate; Vit B2, vitamin B2 (riboflavin); Vit B12, vitamin B12.