1. Mean intracellular pH (pHj) and lactate have been measured simultaneously in the isolated perfused rat liver on two successive occasions separated by an interval of 20 min. In some experiments extra lactate was added to the perfusion medium immediately after the first measurement of pHj.2. There was a direct relationship between the change in pHj over this interval and the simultaneous change of lactate uptake.3. This finding is consistent with the hypothesis that lactate enters the liver cell at least partly in the ionized form and that its metabolism is accompanied by the effective production of hydroxyl ions.4. These observations are discussed in terms of a possible control mechanism for lactate uptake by the liver.

Understanding the relationship between molecular structure and function represents an important goal of undergraduate life sciences. Although evidence suggests that handling physical models supports gains in student understanding of structure–function relationships, such models have not been widely implemented in biochemistry classrooms. Three‐dimensional (3D) printing represents an emerging cost‐effective means of producing molecular models to help students investigate structure–function concepts. We developed three interactive learning modules with dynamic 3D printed models to help biochemistry students visualize biomolecular structures and address particular misconceptions. These modules targeted specific learning objectives related to DNA and RNA structure, transcription factor‐DNA interactions, and DNA supercoiling dynamics. We also designed accompanying assessments to gauge student learning. Students responded favorably to the modules and showed normalized learning gains of 49% with respect to their ability to understand and relate molecular structures to biochemical functions. By incorporating accurate 3D printed structures, these modules represent a novel advance in instructional design for biomolecular visualization. We provide instructors with the materials necessary to incorporate each module in the classroom, including instructions for acquiring and distributing the models, activities, and assessments. © 2019 International Union of Biochemistry and Molecular Biology, 47(3):303–317, 2019.

Prostate epithelial cells control the potency and availability of androgen hormones in part by inactivation and elimination. UDP-glucose dehydrogenase (UGDH) catalyzes the NAD+-dependent oxidation of UDP-glucose to UDP-glucuronate, an essential precursor for androgen inactivation by the prostate glucuronidation enzymes UGT2B15 and UGT2B17. UGDH expression is androgen stimulated, which increases the production of UDP-glucuronate, and fuels UGT-catalyzed glucuronidation. In this study, we compared the glucuronidation potential and its impact on androgen-mediated gene expression in an isogenic LNCaP model for androgen dependent versus castration resistant prostate cancer. Despite significantly lower androgen-glucuronide output, LNCaP 81 castration resistant tumor cells expressed higher levels of UGDH, UGT2B15, and UGT2B17. However, the magnitude of androgen-activated UGDH and PSA expression, as well as the AR-dependent repression of UGT2B15 and UGT2B17, was blunted several-fold in these cells. Consistent with these results, the ligand-activated binding of AR to the PSA promoter and subsequent transcriptional activation were also significantly reduced in castration resistant cells. Analysis of the UDP-sugar pools and flux through pathways downstream of UDP-glucuronate production revealed that these glucuronidation precursor metabolites were channeled through proteoglycan and glycosaminoglycan biosynthetic pathways, leading to increased surface expression of Notch 1. Knockdown of UGDH diminished Notch1 and increased glucuronide output. Overall, these results support a model in which the aberrant partitioning of UDP-glucuronate and other UDP-sugars into alternative pathways during androgen deprivation contributes to the loss of prostate tumor cell androgen sensitivity by promoting altered cell surface proteoglycan expression.

3D printing represents an emerging technology with significant potential to advance life-science education by allowing students to directly explore the relationship between macromolecular structure and function. In this article and supplemental video guide, we describe our development of a model-based instructional module on DNA supercoiling and outline practical tips for implementing models in undergraduate classrooms. We also present a procedure to design and print 3D dynamic models for classroom use. Furthermore, we describe repositories of 3D biomolecule files to make using models accessible and cost-effective.