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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Structure-based optimization of hydroxylactam as potent, cell-active inhibitors of lactate dehydrogenase

Structure-based design was utilized to optimize 6,6-diaryl substituted dihydropyrone and hydroxylactam to obtain inhibitors of lactate dehydrogenase (LDH) with low nanomolar biochemical and single-digit micromolar cellular potencies. Surprisingly the replacement of a phenyl with a pyridyl moiety in the chemical structure revealed a new binding mode for the inhibitors with subtle conformational change of the LDHA active site. Finally, this led to the identification of a potent, cell-active hydroxylactam inhibitor exhibiting an in vivo pharmacokinetic profile suitable for mouse tumor xenograft study.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Mechanism and Dynamics of Photodecarboxylation Catalyzed by Lactate Monooxygenase

Photoenzymes are a rare class of biocatalysts that use light to facilitate chemical reactions. Many of these catalysts utilize a flavin cofactor to absorb light, suggesting that other flavoproteins might have latent photochemical functions. Lactate monooxygenase is a flavin-dependent oxidoreductase previously reported to mediate the photodecarboxylation of carboxylates to afford alkylated flavin adducts. While this reaction holds a potential synthetic value, the mechanism and synthetic utility of this process are unknown. Here, we combine femtosecond spectroscopy, site-directed mutagenesis, and a hybrid quantum-classical computational approach to reveal the active site photochemistry and the role the active site amino acid residues play in facilitating this decarboxylation. Light-induced electron transfer from histidine to flavin was revealed, which has not been reported in other proteins. These mechanistic insights enable the development of catalytic oxidative photodecarboxylation of mandelic acid to produce benzaldehyde, a previously unknown reaction for photoenzymes. Furthermore, our findings suggest that a much wider range of enzymes have the potential for photoenzymatic catalysis than has been realized to date.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Knowledge of lactation amenorrhea method among postpartum women in Ethiopia: a facility-based cross-sectional study

While the importance of knowledge about contraceptives in improving their utilization and thereby reducing the risk of unintended pregnancies is well documented, there are limited studies documented about the Lactational Amenorrhea Method (LAM). Thus, understanding the knowledge of postpartum mothers about LAM is essential for designing tailored interventions. This study assessed the level of knowledge about LAM and its associated factors among postpartum mothers in Ethiopia. A facility-based cross-sectional study was conducted among 3148 randomly selected postpartum participants. The study utilized multistage sampling approach in hospitals located across five regions and one city administration in Ethiopia. Data were collected using face-to-face interviews at discharge. A participant was categorized as having knowledge of LAM if she correctly answered the three LAM criteria: amenorrhea, the first 6 months, and exclusive breast feeding. A binary logistic regression model was used to identify factors associated with knowledge of LAM. Variables with p < 0.25 in the binary logistic regression were included in the multiple logistic regression. Then, associations were described using the adjusted odds ratio (AOR) along with the 95% confidence interval (CI), and statistical significance was declared at p < 0.05. Only four in 10 participants (40.6%; 95% CI 38.9–42.3) had knowledge of LAM. Participants who attended college or above educational level (AOR = 2.1, 95% CI 1.5–2.8), those with parity of two (AOR = 2.3; 95% CI 1.6–3.6) or more than two (AOR = 2.4; 95% CI 1.5–4.0), those who expressed a desire for further fertility (AOR = 1.3; 95% CI 1.1–1.5), individuals who received counselling on LAM (AOR = 3.0; 95% CI 2.6–3.7), and those who gave birth in hospital (AOR = 2.6; 95% CI 1.4–2.6) had higher odds of knowledge about LAM, compared to their counter parts. In contrary, participants resided far away from health facilities had 30% lower odd of knowledge about LAM compared to those resided near the health facilities (AOR = 0.70; 95% CI 0.6–0.8). The proportion of participants who had knowledge of LAM was low. Strengthening counseling about LAM during antenatal care and delivery with due attention to women with limited access to health facilities should be considered for increasing their level of knowledge on LAM.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1972

Stabilization of lactate dehydrogenase

Addition of substances such as dimethylsulfoxide, glycerol, and gelatin to aqueous solutions of lactate dehydrogenase maintains enzymes in stable and fully active form when stored at 2 - 6 C.

Friedman, O. M.↗
DOE OSTI2020

Substrate Channeling via a Transient Protein-Protein Complex: The case of D-Glyceraldehyde-3-Phosphate Dehydrogenase and L-Lactate Dehydrogenase

Molecular dynamics studies showed that LDH and GAPDH tetramers can form a complex which can breakdown when the enzymes are saturated with NADH molecules. The interaction sites are conserved between LDH isozymes from heart and muscle cells, and between GAPDH molecules from rabbit and yeast cells. Positive electric fields between the NAD(H) binding sites showed that NAD(H) channeling within LDH-GAPDH complex can be an extension of NAD(H) channeling between the adjacent subunits within LDH and GAPDH tetramers. Analytical ultracentrifugation and enzyme kinetics studies indicated that LDH and GAPDH molecules can form a transient channeling complex. The transient complex can support the channeled and the diffusive paths in parallel, the relative contribution from each path depends on the off-rates for (GAPDH-NADH)-LDH complex and GAPDH-NADH complex. Negative cooperativity in NADH binding to different subunits in GAPDH tetramers can provide allosteric regulation of NADH channeling from GAPDH to LDH.

INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMI↗