The alcoholic ferment of yeast-juice

Harden, Arthur; Young, William J.

doi:10.1098/rspb.1906.0029

Cited by 124 publications

(34 citation statements)

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“…NAD(P) was discovered in 1906 [160] and subsequent work by Warburg and others in the 1930s, established that its primary function is serving as co-enzyme(s) for the redox reactions in cells [161]. Half a century had since passed before the emergence of evidence indicating that NAD(P) also has important Ca 2+ signaling functions, through serving as substrates for cADPR and NAADP.…”

Section: Resultsmentioning

confidence: 99%

Cyclic ADP-ribose and NAADP: fraternal twin messengers for calcium signaling

Lee

2011

Sci. China Life Sci.

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The concept advanced by Berridge and colleagues that intracellular Ca 2+ -stores can be mobilized in an agonist-dependent and messenger (IP 3 )-mediated manner has put Ca 2+ -mobilization at the center stage of signal transduction mechanisms. During the late 1980s, we showed that Ca 2+ -stores can be mobilized by two other messengers unrelated to inositol trisphosphate (IP 3 ) and identified them as cyclic ADP-ribose (cADPR), a novel cyclic nucleotide from NAD, and nicotinic acid adenine dinucleotide phosphate (NAADP), a linear metabolite of NADP. Their messenger functions have now been documented in a wide range of systems spanning three biological kingdoms. Accumulated evidence indicates that the target of cADPR is the ryanodine receptor in the sarco/endoplasmic reticulum, while that of NAADP is the two pore channel in endolysosomes.As cADPR and NAADP are structurally and functionally distinct, it is remarkable that they are synthesized by the same enzyme. They are thus fraternal twin messengers. We first identified the Aplysia ADP-ribosyl cyclase as one such enzyme and, through homology, found its mammalian homolog, CD38. Gene knockout in mice confirms the important roles of CD38 in diverse physiological functions from insulin secretion, susceptibility to bacterial infection, to social behavior of mice through modulating neuronal oxytocin secretion. We have elucidated the catalytic mechanisms of the Aplysia cyclase and CD38 to atomic resolution by crystallography and site-directed mutagenesis. This article gives a historical account of the cADPR/NAADP/CD38-signaling pathway and describes current efforts in elucidating the structure and function of its components.cyclic ADP-ribose, cADPR, NAADP, nicotinic acid adenine dinucleotide phosphate, CD38, ADP-ribosyl cyclase, Calcium mobilization and signaling Citation:Lee H C. Cyclic ADP-ribose and NAADP: fraternal twin messengers for calcium signaling. Sci China Life Sci, 2011Sci, , 54: 699 -711, doi: 10.1007 In 1983, Berridge and colleagues published a study showing that agonists, such as carbachol, can activate Ca 2+ release from non-mitochondrial Ca 2+ stores and the effect is mediated by a Ca 2+ messenger, inositol 1,4,5-trisphosphate (IP 3 ) [1]. The targeted Ca 2+ stores were later identified as the endoplasmic reticulum (ER), which has since been shown to be the major intracellular Ca 2+ stores. This seminal study ushered in the current field of Ca 2+ signaling as we know it and has made the field center stage. IP 3 is derived from a phospholipid, phosphatidyl inositol 4,5-bisphosphate, present on the cytoplasmic side of the plasma membrane. Agonist binding to its specific receptor leads to activation of phospholipase C and the hydrolysis of the phospholipid, releasing the head group that is IP 3 . The structure of IP 3 is shown in Figure 1. It has three phosphates on the inositol ring. Both the number of phosphates and the position of the phosphates are critical to the binding of IP 3 to its receptor in the ER. The space-filling model of IP 3 shown in Figu...

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Section: Resultsmentioning

confidence: 99%

Cyclic ADP-ribose and NAADP: fraternal twin messengers for calcium signaling

Lee

2011

Sci. China Life Sci.

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“…The integrals were compared with those of α-ATP, in which its brain concentration was set to 2.8 mM (17, 21); thus, the concentrations of intracellular NADH and NAD + in each brain were determined, and the NAD + /NADH RX and total intracellular NAD concentration ([NAD] total = [NAD + ] + [NADH]) were calculated. The NAD + /NADH RP can be calculated using the Nernst Equation (46, 47): RP = RP 0 + RT zF ln ½NAD + ½NADH = RP 0 + RT zF lnðRXÞ, [1] where RP 0 (−0.32 V) is the midpoint potential of the NAD + /NADH redox pair, R is the universal gas constant, T is the absolute temperature, F is the Faraday constant, and z is the number of moles of electrons transferred in the redox reaction (2 for the NAD + /NADH redox reaction). Hence, at the brain temperature of 37°C, RP = −0:32 + 0:0308 log 10 ðRXÞðvoltÞ: [2] To evaluate the reliability of the NAD quantification method and its dependence on the SNR α-ATP in a 31 P MR spectrum, five different levels of randomly generated white Gaussian noise were added to the simulated 7-T 31 P spectra with predetermined HLW and NAD + /NADH ratio values.…”

Section: Methodsmentioning

confidence: 99%

“…redox state | NAD | in vivo 31 P MR spectroscopy | human brain | aging N AD, a multifunctional metabolite found in all living cells, has been the interest of many scientific investigations since its discovery in the early 20th century (1). NAD is known to convert between its oxidized NAD + and reduced NADH forms during the breakdown of nutrients; hence, the intracellular NAD + /NADH redox state reflects the metabolic balance of the cell in generating ATP energy through oxidative phosphorylation in mitochondria and/or glycolysis in cytosol (2).…”

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confidence: 99%

In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences

Zhu

Lü

Lee

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

374

347

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NAD is an essential metabolite that exists in NAD + or NADH form in all living cells. Despite its critical roles in regulating mitochondrial energy production through the NAD + /NADH redox state and modulating cellular signaling processes through the activity of the NAD + -dependent enzymes, the method for quantifying intracellular NAD contents and redox state is limited to a few in vitro or ex vivo assays, which are not suitable for studying a living brain or organ. Here, we present a magnetic resonance (MR) -based in vivo NAD assay that uses the high-field MR scanner and is capable of noninvasively assessing NAD + and NADH contents and the NAD + /NADH redox state in intact human brain. The results of this study provide the first insight, to our knowledge, into the cellular NAD concentrations and redox state in the brains of healthy volunteers. Furthermore, an age-dependent increase of intracellular NADH and age-dependent reductions in NAD + , total NAD contents, and NAD + /NADH redox potential of the healthy human brain were revealed in this study. The overall findings not only provide direct evidence of declined mitochondrial functions and altered NAD homeostasis that accompany the normal aging process but also, elucidate the merits and potentials of this new NAD assay for noninvasively studying the intracellular NAD metabolism and redox state in normal and diseased human brain or other organs in situ.redox state | NAD | in vivo 31 P MR spectroscopy | human brain | aging N AD, a multifunctional metabolite found in all living cells, has been the interest of many scientific investigations since its discovery in the early 20th century (1). NAD is known to convert between its oxidized NAD + and reduced NADH forms during the breakdown of nutrients; hence, the intracellular NAD + /NADH redox state reflects the metabolic balance of the cell in generating ATP energy through oxidative phosphorylation in mitochondria and/or glycolysis in cytosol (2). More recently, after several protein families associated with cell survival were found to use NAD + as their main substrate with activities also regulated by the availability of the NAD + , the full extent of the NAD's function as a metabolic regulator began to unfold (3-5). A growing number of studies have indicated that NAD + can modulate metabolic signaling pathways and mediate important cellular processes, including calcium homeostasis, gene expression, aging, degeneration, and cell death; therefore, the cellular NAD could serve as a therapeutic target for treating various metabolic or age-related diseases and promoting longevity (6-12).Despite the critical relevance of the intracellular NAD metabolism to human health and diseases, assessment of NAD contents and NAD + /NADH redox state is extremely challenging. Only a few invasive techniques based on biochemical assays or autofluorescence methods have been used to analyze tissue samples or cell extracts (13,14). However, during the preparation of such ex vivo sample, the NAD + and NADH contents are likely altered, beca...

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“…355 with energy transfer" for the process. The first step of the process is the accumulation of energy in the form of fructose 1,6-diphosphate (FDP) by yeast fermentation of sugar, based on the Harden-Young effect (11) ; the second is the coupling of the fermentation of FDP with endergonic reactions (energy-utilizing system) through an ATP-ADP system. The energy-utilizing system can involve the enzymes of yeast itself or those of other organisms.…”

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confidence: 99%

Glutamine production in high concentrations with energy transfer employing glutamine synthetase from Micrococcus glutamicus.

Tachiki

Suzuki

Wakisaka

et al. 1983

J. Gen. Appl. Microbiol.

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Glutamine was produced by coupling the glutamine synthetase from Micrococcus glutamicus with sugar fermentation of baker's yeast as an energy-generating system. With 429 units/ml of glutamine synthetase and 40 mg/ml of yeast cells, 120 mM of glutamate was converted completely to glutamine in 3-4 hr, and 160-170 mM of glutamine (approximately 23-25 g/l) was formed in 5 hr from 350 mM of the substrates glutamate and ammonium chloride with a yield of about 40%, based on the energy released by the yeast during sugar fermentation. The activity ratio of sugar fermentation and glutamine synthetase was again confirmed to be important for achievement of energy-coupling in systems with high concentrations of glutamate and ammonium chloride. Glutamine formation was partially stimulated by the addition of Mg2+ in concentrations at which yeast fermentation of sugar showed no response to the cation, but was greatly stimulated by the addition of a small amount of Cott This same Co2+ effect was also observed in the reaction with cell-free extracts or toluol-treated cells of M. glutamicus.We have established processes for the production of various substances, employing dried yeast cells as an enzyme source (1-9). The processes are driven by the energy released by the alcoholic fermentation of sugar by the yeast. We have also designed a new process in which the yeast fermentation of sugar is combined with an endergonic reaction catalyzed by an enzyme from a different microorganism (4, 10). The results suggest that the process offers the possibility of producing many compounds in high yield by using various biosynthetic reactions and high concentrations of substrates. We introduced the term "coupled fermentation 1 Amino acids are L-isomer unless otherwise stated .

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The alcoholic ferment of yeast-juice

Cited by 124 publications

References 0 publications

Cyclic ADP-ribose and NAADP: fraternal twin messengers for calcium signaling

Cyclic ADP-ribose and NAADP: fraternal twin messengers for calcium signaling

In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences

Glutamine production in high concentrations with energy transfer employing glutamine synthetase from Micrococcus glutamicus.

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