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Markedly higher average sucrose (58.1%) was recovered from mesocarp tissue of six orange-flesh cantaloupe (Cucumis melo L.) genotypes over three seasons compared to glucose (17.5%) and fructose (25.6%). A significant decrease in sucrose concentration was observed in the fall for all six genotypes, and the glucose (21.2%) and fructose (33.5%) ratios were also higher in the fall; markedly different than the spring fruit averages. The female inbreds had significantly (P = 0.05) lower glucose, fructose, sucrose, and total sugars than the commercial hybrids. Compared to the male and female inbreds, commercial hybrids had significantly (P = 0.05) higher concentrations of fructose, sucrose and total sugars, but not glucose. Two refractometric digital measures of °Brix (°Brix-At and °Brix-II) in homogenized slurries were positively correlated (r = 0.914; P ≤ 0.001), and were also correlated with total sugars (r ≥ 0.839) and sucrose (r ≥ 0.752). °Brix of cubes (°Brix-cube) was significantly correlated with sucrose and total sugars (r ≥ 0.627). Total sugar was positively correlated with sucrose (r = 0.843; P ≤ 0.001). Eastern-type U.S. melons had significantly (P = 0.05) higher °Brix-cube and °Brix-At compared to U.S. western shipper-types. Female inbreds were significantly (P = 0.05) lower in mean °Brix (all three measures) compared to the hybrids and male inbreds, and female inbreds had higher pH than the male inbreds. Western shippers had significantly (P = 0.05) higher pH compared to eastern genotypes. The predominant organic acid in all six genotypes was succinic acid, generally followed by oxalic, citric/isocitric, then malic acid. Succinic acid recovery was significantly higher in all six genotypes harvested in the fall, compared to spring. Eastern genotypes had significantly (P = 0.05) lower organic acids compared to western genotypes. Results indicate that maternal inheritance appears to confer lower sugar accumulating capacity and higher pH, which, is associated with vacuolar acid invertase (AI) and hexose balance. Breeding programs should focus on hybrid vigor derived through accentuating homozygous female inbreds with lower pH and higher capacity for sucrose accumulation, as well as morphological and agronomic traits often carried in the female line.