Mitochondrial DNA analysis reveals substantial Native American ancestry in Puerto Rico.

To estimate the maternal contribution of Native Americans to the human gene pool of Puerto Ricans--a population of mixed African, European, and Amerindian ancestry--the mtDNAs of two sample sets were screened for restriction fragment length polymorphisms (RFLPs) defining the four major Native American haplogroups. The sample set collected from people who claimed to have a maternal ancestor with Native American physiognomic traits had a statistically significant higher frequency of Native American mtDNAs (69.6%) than did the unbiased sample set (52.6%). This higher frequency suggests that, despite the fact that the native Taíno culture has been extinct for centuries, the Taíno contribution to the current population is considerable and some of the Taíno physiognomic traits are still present. Native American haplogroup frequency analysis shows a highly structured distribution, suggesting that the contribution of Native Americans foreign to Puerto Rico is minimal. Haplogroups A and C cover 56.0% and 35.6% of the Native American mtDNAs, respectively. No haplogroup D mtDNAs were found. Most of the linguistic, biological, and cultural evidence suggests that the Ceramic culture of the Taínos originated in or close to the Yanomama territory in the Amazon. However, the absence of haplogroup A in the Yanomami suggests that the Yanomami are not the only Taíno ancestors.

Inhibition of recombinant human mitochondrial aldehyde dehydrogenase by two intermediate metabolites of disulfiram.

Disulfiram is used in aversion therapy for alcoholism. S-Methyl-N,N-diethylthiocarbamate (MeDTC) sulfoxide, a potent inhibitor of the target enzyme mitochondrial aldehyde dehydrogenase (ALDH2), is thought to be the principal active metabolite of disulfiram in vivo. We examined the effects on recombinant human ALDH2 of two intermediate metabolites of disulfiram, S-methyl-N,N-diethyldithiocarbamate (MeDDC) sulfoxide and MeDDC sulfine. MeDDC sulfoxide was a potent inhibitor of ALDH2 with an IC50 of 2.2 +/- 0.5 microM (mean +/- SD, N = 4) after preincubation with enzyme for 30 min. MeDDC sulfine was a relatively weak inhibitor of ALDH2 under the same conditions with an IC50 value of 62 +/- 14 microM. The inhibition of ALDH2 by both compounds was irreversible and did not require the cofactor NAD. The latter finding demonstrates that inactivation of ALDH2 is independent of the dehydrogenase activity of the enzyme. GSH blocked almost completely the inhibition by 20 microM of MeDDC sulfoxide and greatly diminished the inhibition by 200 microM of MeDDC sulfine. Inactivation by MeDDC sulfoxide was time dependent. MeDTC sulfoxide was a more potent inhibitor of recombinant human ALDH2 (IC50 = 1.4 +/- 0.3 microM after preincubation for 15 min) than either of the intermediate metabolites, and its inhibition was unaffected by GSH. Our results suggest that these newer intermediate metabolites of disulfiram, especially the more potent MeDTC sulfoxide, have the potential to inhibit the target enzyme ALDH2 in patients receiving disulfiram. However, until the significance of the interactions of the inhibitors with GSH is more fully understood, the contribution of MeDDC sulfine and MeDDC sulfoxide to the pharmacological effects of disulfiram in vivo is uncertain.