Journal: The Journal of Biological Chemistry

Article Title: De novo synthesis of serine and glycine fuels purine nucleotide biosynthesis in human lung cancer tissues

doi: 10.1074/jbc.RA119.008743

Figure Lengend Snippet: Activation of Ser/Gly synthesis from glucose, their efficient incorporation into purines, and reverse flux of the Ser–Gly one-carbon pathway underlie preference for glucose as substrate for purine synthesis in lung cancer tissues ex vivo. The three schemes depict our key findings on the metabolism of exogenous glucose (a), Ser (b), and Gly (c) into purines in CA lung tissues. These were modified from the mammalian cell literature (4, 32, 40,–43). a, 1) net [13C3]glucose (Glc) uptake, enhanced conversion to [13C]Ser/[13C2]Gly in the cytoplasm (pool 1, light green square), and efficient incorporation (thick red arrow) into purine carbons (red circle) (e.g. adenine of ATP) via the action of cytoplasmic SHMT1 (route 1), MTHFD1 (route 2), and other enzymes (not shown) in the purine nucleotide synthesis pathway; 2) lack of cytoplasmic and mitochondrial exchange for [13C3]Ser/[13C2]Gly. b, 3) net uptake of exogenous D3-Ser into the cytoplasm (pool 2, peach square), which does not readily exchange with pool 1 but exchanges with the mitochondrial pool (lavender square) and interconverts with Gly and one-carbon metabolites (green double-headed arrow); 4) less access of D3-Ser-derived Gly and one carbon metabolites (peach square pools) to purine synthesis machinery (e.g. orange square purinosomes (44)); 5) enhanced mitochondrial Gly to Ser fluxes (uneven green double-headed arrow) possibly driven by activation of SHMT2 and MTHFD2 (thick green double-headed arrow). b and c, 6) loss of D (or gain of H) in one carbon metabolites via mitochondrial MTHFD2/2L and cytoplasmic MTHFD1 exchange reactions (green double-headed arrow); 7) loss of D via direct incorporation of D-Gly into C5,6 of purines (thin arrow); 8) negligible incorporation of Gly-derived one carbon metabolites into purines (gray arrow). c, 9) net Gly efflux (uneven arrow); 9) less favored direct (route 1, thin blue arrow) (c) and indirect (route 2, not depicted) incorporation of [13C2]Gly into purines. PSAT1, phosphoserine aminotransferase; MTHFD1, cytoplasmic NADP+-dependent methylene tetrahydrofolate (CH2-THF) dehydrogenase/methylene THF; cyclohydrolase/formyl THF (CHO-THF) synthetase; MTHFD2, mitochondrial NAD+-dependent methylene THF dehydrogenase/methylene THF cyclohydrolase; MTHFD2L, mitochondrial NADP+-dependent methylene THF dehydrogenase; MTHFD1L, mitochondrial formyl THF synthetase; 3-PG, 3-phosphoglycerate; 3-POHPyr, 3-phosphohydroxypyruvate. Solid and dashed arrows: one- and multistep reactions, respectively.

Article Snippet: The primary antibodies used were obtained from ProteinTech Group with the following catalogue numbers: GAPDH, 60004-1-Ig; PSAT1, 10501-1-AP; MTHFD2, 12270-1-AP; SHMT2, 11099-1-AP; and PHGDH, 14719-1-AP; GLDC, 24827-1-AP.

Techniques: Activation Assay, Ex Vivo, Modification, Derivative Assay

Journal: BJU international

Article Title: The relationship between prostate volume and prostate-specific antigen variability: data from the Baltimore Longitudinal Study of Aging and the Johns Hopkins Active Surveillance Program

doi: 10.1111/j.1464-410X.2011.10663.x

Figure Lengend Snippet: Study population age, prostate volume, baseline PSA, and prostate volume measurement intervals (AS and BLSA)

Article Snippet: AS Johns Hopkins Active Surveillance Program BLSA Baltimore Longitudinal Study of Aging PSAV PSA velocity PSAYV PSA yearly variability

Techniques:

Journal: BJU international

Article Title: The relationship between prostate volume and prostate-specific antigen variability: data from the Baltimore Longitudinal Study of Aging and the Johns Hopkins Active Surveillance Program

doi: 10.1111/j.1464-410X.2011.10663.x

Figure Lengend Snippet: BLSA population: mean PSAYV by prostate volume quartile

Article Snippet: AS Johns Hopkins Active Surveillance Program BLSA Baltimore Longitudinal Study of Aging PSAV PSA velocity PSAYV PSA yearly variability

Techniques:

Journal: BJU international

Article Title: The relationship between prostate volume and prostate-specific antigen variability: data from the Baltimore Longitudinal Study of Aging and the Johns Hopkins Active Surveillance Program

doi: 10.1111/j.1464-410X.2011.10663.x

Figure Lengend Snippet: BLSA population: mean PSAYV/baseline PSA by prostate volume quartile

Article Snippet: AS Johns Hopkins Active Surveillance Program BLSA Baltimore Longitudinal Study of Aging PSAV PSA velocity PSAYV PSA yearly variability

Techniques:

Journal: BJU international

Article Title: The relationship between prostate volume and prostate-specific antigen variability: data from the Baltimore Longitudinal Study of Aging and the Johns Hopkins Active Surveillance Program

doi: 10.1111/j.1464-410X.2011.10663.x

Figure Lengend Snippet: AS population: mean PSAYV by prostate volume quartile

Article Snippet: AS Johns Hopkins Active Surveillance Program BLSA Baltimore Longitudinal Study of Aging PSAV PSA velocity PSAYV PSA yearly variability

Techniques:

Journal: BJU international

Article Title: The relationship between prostate volume and prostate-specific antigen variability: data from the Baltimore Longitudinal Study of Aging and the Johns Hopkins Active Surveillance Program

doi: 10.1111/j.1464-410X.2011.10663.x

Figure Lengend Snippet: AS population: mean PSAYV/baseline PSA by prostate volume quartile

Article Snippet: AS Johns Hopkins Active Surveillance Program BLSA Baltimore Longitudinal Study of Aging PSAV PSA velocity PSAYV PSA yearly variability

Techniques:

Journal: BJU international

Article Title: The relationship between prostate volume and prostate-specific antigen variability: data from the Baltimore Longitudinal Study of Aging and the Johns Hopkins Active Surveillance Program

doi: 10.1111/j.1464-410X.2011.10663.x

Figure Lengend Snippet: Mean PSAYV by baseline PSA range for the BLSA and AS populations

Article Snippet: AS Johns Hopkins Active Surveillance Program BLSA Baltimore Longitudinal Study of Aging PSAV PSA velocity PSAYV PSA yearly variability

Techniques:

Journal: BJU international

Article Title: The relationship between prostate volume and prostate-specific antigen variability: data from the Baltimore Longitudinal Study of Aging and the Johns Hopkins Active Surveillance Program

doi: 10.1111/j.1464-410X.2011.10663.x

Figure Lengend Snippet: Linear mixed-effects model to predict PSAYV in the BLSA and AS populations, adjusting for age, baseline PSA and prostate volume

Article Snippet: AS Johns Hopkins Active Surveillance Program BLSA Baltimore Longitudinal Study of Aging PSAV PSA velocity PSAYV PSA yearly variability

Techniques: