Paul Yancey | Whitman College (original) (raw)

Papers by Paul Yancey

Paracelsus Proceedings of Experimental Medicine, Sep 18, 2023

This article is licensed under the Creative Commons Attribution 4.0 International License (CC BY)... more This article is licensed under the Creative Commons Attribution 4.0 International License (CC BY). This means that any user shall be free to copy and redistribute the material in any medium or format, also for commercial purposes, provided proper credit is given to the Authors as well as the original publisher.

The Journal of Experimental Biology, Jun 1, 2015

Organisms experience a wide range of environmental factors such as temperature, salinity and hydr... more Organisms experience a wide range of environmental factors such as temperature, salinity and hydrostatic pressure, which pose challenges to biochemical processes. Studies on adaptations to such factors have largely focused on macromolecules, especially intrinsic adaptations in protein structure and function. However, micromolecular cosolutes can act as cytoprotectants in the cellular milieu to affect biochemical function and they are now recognized as important extrinsic adaptations. These solutes, both inorganic and organic, have been best characterized as osmolytes, which accumulate to reduce osmotic water loss. Singly, and in combination, many cosolutes have properties beyond simple osmotic effects, e.g. altering the stability and function of proteins in the face of numerous stressors. A key example is the marine osmolyte trimethylamine oxide (TMAO), which appears to enhance water structure and is excluded from peptide backbones, favoring protein folding and stability and counteracting destabilizers like urea and temperature. Co-evolution of intrinsic and extrinsic adaptations is illustrated with high hydrostatic pressure in deep-living organisms. Cytosolic and membrane proteins and G-protein-coupled signal transduction in fishes under pressure show inhibited function and stability, while revealing a number of intrinsic adaptations in deep species. Yet, intrinsic adaptations are often incomplete, and those fishes accumulate TMAO linearly with depth, suggesting a role for TMAO as an extrinsic 'piezolyte' or pressure cosolute. Indeed, TMAO is able to counteract the inhibitory effects of pressure on the stability and function of many proteins. Other cosolutes are cytoprotective in other ways, such as via antioxidation. Such observations highlight the importance of considering the cellular milieu in biochemical and cellular adaptation.

The journal of experimental zoology, 2001

In shallow marine teleost fishes, the osmolyte trimethylamine oxide (TMAO) is typically found at ... more In shallow marine teleost fishes, the osmolyte trimethylamine oxide (TMAO) is typically found at <70 mmol/kg wet weight. Recently we found deep-sea teleosts have up to 288 mmol/kg, increasing in the order shallow < bathyal < abyssal. We hypothesized that this protein stabilizer counteracts inhibition of proteins by hydrostatic pressure, and showed that, for lactate dehydrogenases (LDH), 250 mM TMAO fully offset an increase in NADH K m at physiological pressure, and partly reversed pressure-enhanced losses of activity at supranormal pressures. In this study, we examined other effects of pressure and TMAO on proteins of teleosts that live from 2000-5000 m (200-500 atmospheres [atm]). First, for LDH from a grenadier (Coryphaenoides leptolepis) at 500 atm for 8 hr, there was a significant 15% loss in activity (P < 0.05 relative to 1 atm control) that was reduced with 250 mM TMAO to an insignificant loss. Second, for pyruvate kinase from a morid cod (Antimora microlepis) at 200 atm, there was 73% increase in ADP K m without TMAO (P < 0.01 relative to K m at 1 atm) but only a 29% increase with 300 mM TMAO. Third, for G-actin from a grenadier (C. armatus) at 500 atm for 16 hr, there was a significant reduction of F-actin polymerization (P < 0.01 compared to polymerization at 1 atm) that was fully counteracted by 250 mM TMAO, but was unchanged in 250 mM glycine. These findings support the hypothesis.

Dataset: HADES-K Sediment Macrofaunal DiversityThis dataset includes raw counts of macrofauna fam... more Dataset: HADES-K Sediment Macrofaunal DiversityThis dataset includes raw counts of macrofauna families identified in push core samples taken in the Kermadec Trench in the Southwest Pacific, 4000 to ~10,000m from the RV/ Thomas G. Thompson during cruise TN309 (HADES-K), May 2014. For a complete list of measurements, refer to the full dataset description in the supplemental file 'Dataset_description.pdf'. The most current version of this dataset is available at: https://www.bco-dmo.org/dataset/763694NSF Division of Ocean Sciences (NSF OCE) OCE-113162

Brain Research, Sep 1, 1995

Cell volume regulation is a vital biological function in all species. Maintenance of cerebral cel... more Cell volume regulation is a vital biological function in all species. Maintenance of cerebral cell size in the face of osmotic stress is especially important because the brain is contained in the non-compliant skull. The developmental aspects of this adaptive process are not known. Therefore, we evaluated cerebral cell volume regulation during hypematremia in pre-weaning and adult rats. Hypernatremia was induced by injections of 1 M NaC1 for 48 h. Brain water, electrolyte, and organic osmolyte contents were measured in hypernatremic and sham injected littermate control rats at the following ages: 12, 18 and 20 days and adults. In normonatremic rats, there was a steady decline in brain water content during development that was paralleled by a gradual fall in the cerebral levels of Na +, K +, and all organic osmolytes. The change in brain water content correlated most closely with the decrease in cerebral taurine content. In the face of equivalent elevations in serum Na + concentration, there was comparable brain cell shrinkage and similar increases in total cerebral electrolyte and organic osmolyte content in rats at all 4 ages studied. Taurine was the predominant organic osmolyte prior to weaning, constituting 16-49% of the increment in nonperturbing solute content in hypernatremic animals between 12-20 days of age; in contrast, taurine contributed only 10% to the cerebral organic osmolyte pool in adult rats. We conclude that the capacity of brain cells to accumulate inorganic electrolytes and organic osmolytes during adaptation to hypernatremia is adequately expressed in developing rats, aged 12 days and older. Moreover, we speculate that the immature animal behaves as if it has an elevated 'set point' to protect the higher brain water content that is present earlier in development.

Comparative Biochemistry and Physiology A-molecular & Integrative Physiology, Nov 1, 2002

Shallow-living marine invertebrates use free amino acids as cellular osmolytes, while most teleos... more Shallow-living marine invertebrates use free amino acids as cellular osmolytes, while most teleosts use almost no organic osmolytes. Recently we found unusual osmolyte compositions in deep-sea animals. Trimethylamine N-oxide (TMAO) increases with depth in muscles of some teleosts, skates, and crustaceans (up to 300 mmolykg at 2900 m). Other deep-sea animals had high levels of (1) scyllo-inositol in echinoderms, gastropods, and polychaetes, (2) that polyol plus b-alanine and betaine in octopods, (3) hypotaurine, N-methyltaurine, and unidentified methylamines in vestimentiferans from hydrothermal vents and cold seeps, and (4) a depth-correlated serine-phosphate osmolyte in vesicomyid clams from trench seeps. We hypothesize that some of these solutes counteract effects of hydrostatic pressure. With lactate dehydrogenase, actin, and pyruvate kinase, 250 mM TMAO (but not glycine) protected both ligand binding and protein stability against pressure. To test TMAO in living cells, we grew yeast under pressure. After 1 h at 71 MPa, 3.5 h at 71 MPa, and 17 h at 30 MPa, 150 mM TMAO generally doubled the number of cells that formed colonies. Sulfur-based osmolytes which are not correlated with depth, such as hypotaurine and thiotaurine, are probably involved in sulfide metabolism and detoxification. Thus deep-sea osmolytes may have at least two other roles beyond acting as simple compatible osmotica.

Comparative Biochemistry and Physiology Part C: Comparative Pharmacology, Nov 1, 1992

The mammalian renal medulla uses sorbitol, myo-jnositol, betaine and gIycerophosphorylcholine as ... more The mammalian renal medulla uses sorbitol, myo-jnositol, betaine and gIycerophosphorylcholine as intracellular osmotytes. 2. Sorbitol synthesis was inhibited by feeding male Wistar rats the aldose reductase inhibitor sorbinil at 40 mg/kg/day for 71 d, and renal inner medullas were extracted for analysis. 3. Aldose reductase activities and sorbitol contents were greatly reduced in sorbinil-treated animals, while betaine contents increased significantly (with no other osmolytes changing). 4. The betaine increase compensated for the sorbitol decrease such that the total organic osmolytes maintained the same ratio to sodium contents as controls. 5. These results are identical to the pattern previously reported for sorbinil treatment of rats for 10 d, but not for 21 d.

PubMed, Jun 1, 2004

Most shallow teleosts have low organic osmolyte contents, e.g. 70 mmol/kg or less of trimethylami... more Most shallow teleosts have low organic osmolyte contents, e.g. 70 mmol/kg or less of trimethylamine oxide (TMAO). Our previous work showed that TMAO contents increase with depth in muscles of several Pacific families of teleost fishes, to about 180 mmol/kg wet wt at 2.9 km depth in grenadiers. We now report that abyssal grenadiers (Coryphaenoides armatus, Macrouridae) from the Atlantic at 4.8 km depth contain 261 mmol/kg wet wt in muscle tissue. This precisely fits a linear trend extrapolated from the earlier data. We also found that anemones show a trend of increasing contents of methylamines (TMAO, betaine) and scyllo-inositol with increasing depth. Previously we found that TMAO counteracts the inhibitory effects of hydrostatic pressure on a variety of proteins. We now report that TMAO and, to a lesser extent, betaine, are generally better stabilizers than other common osmolytes (myo-inositol, taurine and glycine), in terms of counteracting the effects of pressure on NADH Km of grenadier lactate dehydrogenase and ADP Km of anemone and rabbit pyruvate kinase.

Biochimica Et Biophysica Acta - General Subjects, Jun 1, 1987

Temperature effects on dissociation constants (Kd), binding enthalpies and apparent Michaelis con... more Temperature effects on dissociation constants (Kd), binding enthalpies and apparent Michaelis constants (Km) for NADH, plus Arrhenius activation energies (Ea), substrate turnover numbers (kcat), and NADH &#39;on&#39; constants (k1) were measured or calculated for M4-lactate dehydrogenase homologs from deep-sea, midwater, shallow-water temperate, and shallow-water tropical teleost fishes, and a mammal. At any single measurement temperature, Km and kcat values were significantly higher for groups adapted to lower temperatures. This pattern of Km values and temperature illustrates a strong evolutionary conservation of Km of NADH. When determined at the average body temperature of each species, the Km values are very similar, resulting in the preservation of the catalytic capacity and regulatory properties of these enzyme homologs at their in situ temperatures. In contrast, Kd values, while varying considerably among species, are not significantly different among the different groups at any one temperature. The ratio of Km to Kd tends to follow a phylogenetic pattern rather than a pattern of environmental adaptation. Thus, evolutionary adjustments in Km are not directly the result of changes in cofactor binding. All the rate constants involved in determining the Km and Kd of NADH (kcat, k1 and k-1) can be modified.

American Journal of Physiology-renal Physiology, May 1, 1989

A simple high performance liquid chromatography (HPLC) method of separating and quantitating the ... more A simple high performance liquid chromatography (HPLC) method of separating and quantitating the predominant organic solutes of the renal medulla is described. These organic solutes include myo-inositol, glycerophosphorylcholine, sorbitol, betaine, and urea. Other physiologically significant solutes, including glucose and mannitol, can be separated and quantitated concurrently with this method. With the use of this technique, the organic solutes of the rabbit kidney were determined. No new organic compounds were detected by HPLC that could significantly contribute to intracellular osmolality of the medulla. The values for the organic solutes already described were similar to those obtained by more complicated and limited approaches such as classical enzymatic techniques, ion electrodes, nuclear magnetic resonance spectroscopy, and gas chromatography-mass spectroscopy.

American zoologist, Aug 1, 2001

SYNOPSIS. Organic osmolytes are small solutes used by cells of numerous waterstressed organisms a... more SYNOPSIS. Organic osmolytes are small solutes used by cells of numerous waterstressed organisms and tissues to maintain cell volume. All known osmolytes are amino acids and derivatives, polyols and sugars, methylamines, and urea; unlike salt ions, most are ''compatible,'' i.e., do not perturb macromolecules. In addition, some stabilize macromolecules and are ''counteracting'' towards perturbants, e.g., methylamines can stabilize proteins and ligand binding against perturbations by urea in elasmobranchs and mammalian kidney, and (our latest findings) high hydrostatic pressure in deep-sea animals. Methylamines appear to coordinate water molecules tightly, resulting in osmolyte exclusion from hydration layers of peptide backbones. This makes unfolded protein conformations entropically unfavorable (work of Timasheff, Galinski, Bolen and coworkers). These properties have led to proposed uses in biotechnology, agriculture and medicine, including improved biochemical methods, in vitro rescue of misfolded proteins in cystic fibrosis and prion diseases (work of Welch and others), and plants engineered for drought and salt tolerance. These properties also explain some but not all of the considerable variation in osmolyte composition among species with different metabolisms and habitats, and among and within mammalian tissues in development.

Biological and Chemical Oceanography Data Management Office, Mar 18, 2019

Dataset: HADES-K Sediment Meiofaunal DiversityThis dataset includes raw counts of meiofauna ident... more Dataset: HADES-K Sediment Meiofaunal DiversityThis dataset includes raw counts of meiofauna identified in push core samples taken in the Kermadec Trench in the Southwest Pacific, 4000 to ~10,000m from the RV/ Thomas G. Thompson during cruise TN309 (HADES-K), May 2014. For a complete list of measurements, refer to the full dataset description in the supplemental file 'Dataset_description.pdf'. The most current version of this dataset is available at: https://www.bco-dmo.org/dataset/763758NSF Division of Ocean Sciences (NSF OCE) OCE-113162

Kidney International, Aug 1, 1995

Time-dependent aspects of osmolyte changes in rat kidney, urine, blood and lens with sorbinil and... more Time-dependent aspects of osmolyte changes in rat kidney, urine, blood and lens with sorbinil and galactose feeding. Sorbitol plus myo-inositol, betame and glycerophosphorylcholine (GPC) are cellular osmolytes in the mammalian renal medulla. Galactosemia and hyperglycemia can cause excessive levels of galactitol or sorbitol in several organs via aldose reductase (AR) catalysis. AIR inhibitors can reduce these polyols. To examine osmolyte responses to polyol perturbations, male Wistar rats were fed normal diet, the AR inhibitor sorbinil (at 40 mg/kg/d), 25% galactose, or a combination, for 10, 21 and 42 days. All animals at 21 days had higher apparent renal AR activity than at 10 or 42 days, possibly providing resistance to sorbinil. Sorbinil feeding alone tended to increase urinary, plasma and renal urea levels. It reduced AR activity and sorbitol contents in renal inner medulla, though less so at 21 days; other renal osmolytes, especially betaine, were elevated. Galactose feeding caused little change in renal AR activity, and resulted in high galactose and galactitol contents in renal medulla, urine, blood and lens (and higher renal Na contents at 10 days). Renal sorbitol, inositol and GPC decreased, while betaine contents trended higher at all times. Sorbinilgalactose feeding reduced renal AR activities and galactitol contents (again less so at 21 days), urine, blood and lens galactitol, and further reduced renal sorbitol contents. At 10 and 21 days it tended to raise renal betaine more, and restore inositol (but not GPC) contents to control levels. At 42 days it reduced renal and urinary Na and galactose, and decreased renal betaine to control levels. Under most conditions, total renal (non-urea) organic osmolyte contents (presumed to be mostly intracellular) and Na plus galactose contents (presumed mostly extracellular) changed together such that cell volumes may have been maintained. The exception was 10 days on galactose, where total osmolytes appeared too low. In galactose-fed animals, urine/plasma ratios suggest some renal galactitol efflux, and cellular galactitol probably helps maintain osmotic balance rather than cause swelling. Mammalian renal medulla cells must cope with high external salt concentrations produced by the kidney's urine-concentrating mechanism. Like cells of a wide variety of organisms exposed to hypertonicity, renal cells apparently maintain cell volume with "compatible" organic osmolytes, solutes which do not exhibit the disruptive effects on macromolecules that occur with high NaC1 or KC1 [1, 2]. Compatible osmolytes in most organisms are polyols, methylamines, and free amino acids [2]; in the mammalian renal medulla, the major ones are sorbitol, myo-inositol, glycerophos

American Journal of Physiology-renal Physiology, Oct 1, 1992

Renal medullary cells contain high levels of (glycine) betaine, glycerophosphorylcholine (GPC), m... more Renal medullary cells contain high levels of (glycine) betaine, glycerophosphorylcholine (GPC), myo-inositol, and sorbitol. Two functions of these have been proposed: 1) that they are compatible osmolytes which regulate cell volume (against high external NaCl) without inhibiting proteins and 2) that methylamines (GPC and betaine) are counteracting osmolytes which stabilize proteins against perturbation from high renal urea. As a test of the latter, osmolyte contents in kidney medullas were measured in rats subjected to three types of dietary manipulation: 1) diets with protein and NaCl contents varied oppositely, 2) diets with a constant low NaCl and varied protein content, and 3) a low-calorie diet. With low-protein and low-calorie diets, only renal contents of urea, GPC, and inositol decreased; betaine and sorbitol contents increased such that contents of total nonurea organic osmolytes remained constant. With high-protein diets, only renal contents of sodium, urea, and GPC increased, with the latter giving total organic osmolytes a consistent correlation to sodium. Across all diets, the only consistent (linear) correlations were 1) between urea and GPC contents, supporting previous suggestions that GPC is the major counteractant to urea, and 2) between total organic osmolytes and sodium (but not urea) contents, as predicted by the compatible osmolytes hypothesis.

American zoologist, Aug 1, 2001

SYNOPSIS. Organic osmolytes are small solutes used by cells of numerous waterstressed organisms a... more SYNOPSIS. Organic osmolytes are small solutes used by cells of numerous waterstressed organisms and tissues to maintain cell volume. All known osmolytes are amino acids and derivatives, polyols and sugars, methylamines, and urea; unlike salt ions, most are ''compatible,'' i.e., do not perturb macromolecules. In addition, some stabilize macromolecules and are ''counteracting'' towards perturbants, e.g., methylamines can stabilize proteins and ligand binding against perturbations by urea in elasmobranchs and mammalian kidney, and (our latest findings) high hydrostatic pressure in deep-sea animals. Methylamines appear to coordinate water molecules tightly, resulting in osmolyte exclusion from hydration layers of peptide backbones. This makes unfolded protein conformations entropically unfavorable (work of Timasheff, Galinski, Bolen and coworkers). These properties have led to proposed uses in biotechnology, agriculture and medicine, including improved biochemical methods, in vitro rescue of misfolded proteins in cystic fibrosis and prion diseases (work of Welch and others), and plants engineered for drought and salt tolerance. These properties also explain some but not all of the considerable variation in osmolyte composition among species with different metabolisms and habitats, and among and within mammalian tissues in development.

Typical mammalian body fluids have osmotic pressures of about 300 mosm/kg, with inorganic ions as... more Typical mammalian body fluids have osmotic pressures of about 300 mosm/kg, with inorganic ions as the major osmotic effectors (osmolytes) both extra- and intracellularly. Many non-mammalian species face much higher osmotic pressures, and comparative physiologists have long known that cells in such organisms generally use organic solutes to maintain osmotic balance. From eubacteria to lower vertebrates, these organic osmolytes appear to fall within a few categories of compounds, namely polyols, neutral amino acids and derivatives, dimethyl-sulfonioproprionate, and urea, usually in combination with methylamines (Yancey et al. 1982; Somero, this Vol.). Only recently has it been fully recognized that some mammalian tissues follow this widespread evolutionary pattern, in particular the kidney. As a consequence of the urine-concentrating mechanism, cells of the renal inner medulla may be exposed to extracellular urea and NaC1 at well over 1000 mosm/kg. In the mid-1980s (Balaban and Knepper 1983; Finely 1984; Bagnasco et al. 1986), it was found that the inner kidney can contain high levels of the polyols sorbitol and (myo)-inositol, and the methylamines betaine and glycerophosphorylcholine (GPC; first detected by Ullrich 1959). These appear to be intracellular (since they are not found in urine or blood), and it was proposed that these compounds serve as osmolytes in renal cell volume maintenance (Fig. 1).

The journal of college science teaching, 1992

Physiological and Biochemical Zoology, 2010

Paracelsus Proceedings of Experimental Medicine, Sep 18, 2023

This article is licensed under the Creative Commons Attribution 4.0 International License (CC BY)... more This article is licensed under the Creative Commons Attribution 4.0 International License (CC BY). This means that any user shall be free to copy and redistribute the material in any medium or format, also for commercial purposes, provided proper credit is given to the Authors as well as the original publisher.

The Journal of Experimental Biology, Jun 1, 2015

Organisms experience a wide range of environmental factors such as temperature, salinity and hydr... more Organisms experience a wide range of environmental factors such as temperature, salinity and hydrostatic pressure, which pose challenges to biochemical processes. Studies on adaptations to such factors have largely focused on macromolecules, especially intrinsic adaptations in protein structure and function. However, micromolecular cosolutes can act as cytoprotectants in the cellular milieu to affect biochemical function and they are now recognized as important extrinsic adaptations. These solutes, both inorganic and organic, have been best characterized as osmolytes, which accumulate to reduce osmotic water loss. Singly, and in combination, many cosolutes have properties beyond simple osmotic effects, e.g. altering the stability and function of proteins in the face of numerous stressors. A key example is the marine osmolyte trimethylamine oxide (TMAO), which appears to enhance water structure and is excluded from peptide backbones, favoring protein folding and stability and counteracting destabilizers like urea and temperature. Co-evolution of intrinsic and extrinsic adaptations is illustrated with high hydrostatic pressure in deep-living organisms. Cytosolic and membrane proteins and G-protein-coupled signal transduction in fishes under pressure show inhibited function and stability, while revealing a number of intrinsic adaptations in deep species. Yet, intrinsic adaptations are often incomplete, and those fishes accumulate TMAO linearly with depth, suggesting a role for TMAO as an extrinsic 'piezolyte' or pressure cosolute. Indeed, TMAO is able to counteract the inhibitory effects of pressure on the stability and function of many proteins. Other cosolutes are cytoprotective in other ways, such as via antioxidation. Such observations highlight the importance of considering the cellular milieu in biochemical and cellular adaptation.

The journal of experimental zoology, 2001

In shallow marine teleost fishes, the osmolyte trimethylamine oxide (TMAO) is typically found at ... more In shallow marine teleost fishes, the osmolyte trimethylamine oxide (TMAO) is typically found at <70 mmol/kg wet weight. Recently we found deep-sea teleosts have up to 288 mmol/kg, increasing in the order shallow < bathyal < abyssal. We hypothesized that this protein stabilizer counteracts inhibition of proteins by hydrostatic pressure, and showed that, for lactate dehydrogenases (LDH), 250 mM TMAO fully offset an increase in NADH K m at physiological pressure, and partly reversed pressure-enhanced losses of activity at supranormal pressures. In this study, we examined other effects of pressure and TMAO on proteins of teleosts that live from 2000-5000 m (200-500 atmospheres [atm]). First, for LDH from a grenadier (Coryphaenoides leptolepis) at 500 atm for 8 hr, there was a significant 15% loss in activity (P < 0.05 relative to 1 atm control) that was reduced with 250 mM TMAO to an insignificant loss. Second, for pyruvate kinase from a morid cod (Antimora microlepis) at 200 atm, there was 73% increase in ADP K m without TMAO (P < 0.01 relative to K m at 1 atm) but only a 29% increase with 300 mM TMAO. Third, for G-actin from a grenadier (C. armatus) at 500 atm for 16 hr, there was a significant reduction of F-actin polymerization (P < 0.01 compared to polymerization at 1 atm) that was fully counteracted by 250 mM TMAO, but was unchanged in 250 mM glycine. These findings support the hypothesis.

Dataset: HADES-K Sediment Macrofaunal DiversityThis dataset includes raw counts of macrofauna fam... more Dataset: HADES-K Sediment Macrofaunal DiversityThis dataset includes raw counts of macrofauna families identified in push core samples taken in the Kermadec Trench in the Southwest Pacific, 4000 to ~10,000m from the RV/ Thomas G. Thompson during cruise TN309 (HADES-K), May 2014. For a complete list of measurements, refer to the full dataset description in the supplemental file 'Dataset_description.pdf'. The most current version of this dataset is available at: https://www.bco-dmo.org/dataset/763694NSF Division of Ocean Sciences (NSF OCE) OCE-113162

Brain Research, Sep 1, 1995

Cell volume regulation is a vital biological function in all species. Maintenance of cerebral cel... more Cell volume regulation is a vital biological function in all species. Maintenance of cerebral cell size in the face of osmotic stress is especially important because the brain is contained in the non-compliant skull. The developmental aspects of this adaptive process are not known. Therefore, we evaluated cerebral cell volume regulation during hypematremia in pre-weaning and adult rats. Hypernatremia was induced by injections of 1 M NaC1 for 48 h. Brain water, electrolyte, and organic osmolyte contents were measured in hypernatremic and sham injected littermate control rats at the following ages: 12, 18 and 20 days and adults. In normonatremic rats, there was a steady decline in brain water content during development that was paralleled by a gradual fall in the cerebral levels of Na +, K +, and all organic osmolytes. The change in brain water content correlated most closely with the decrease in cerebral taurine content. In the face of equivalent elevations in serum Na + concentration, there was comparable brain cell shrinkage and similar increases in total cerebral electrolyte and organic osmolyte content in rats at all 4 ages studied. Taurine was the predominant organic osmolyte prior to weaning, constituting 16-49% of the increment in nonperturbing solute content in hypernatremic animals between 12-20 days of age; in contrast, taurine contributed only 10% to the cerebral organic osmolyte pool in adult rats. We conclude that the capacity of brain cells to accumulate inorganic electrolytes and organic osmolytes during adaptation to hypernatremia is adequately expressed in developing rats, aged 12 days and older. Moreover, we speculate that the immature animal behaves as if it has an elevated 'set point' to protect the higher brain water content that is present earlier in development.

Comparative Biochemistry and Physiology A-molecular & Integrative Physiology, Nov 1, 2002

Shallow-living marine invertebrates use free amino acids as cellular osmolytes, while most teleos... more Shallow-living marine invertebrates use free amino acids as cellular osmolytes, while most teleosts use almost no organic osmolytes. Recently we found unusual osmolyte compositions in deep-sea animals. Trimethylamine N-oxide (TMAO) increases with depth in muscles of some teleosts, skates, and crustaceans (up to 300 mmolykg at 2900 m). Other deep-sea animals had high levels of (1) scyllo-inositol in echinoderms, gastropods, and polychaetes, (2) that polyol plus b-alanine and betaine in octopods, (3) hypotaurine, N-methyltaurine, and unidentified methylamines in vestimentiferans from hydrothermal vents and cold seeps, and (4) a depth-correlated serine-phosphate osmolyte in vesicomyid clams from trench seeps. We hypothesize that some of these solutes counteract effects of hydrostatic pressure. With lactate dehydrogenase, actin, and pyruvate kinase, 250 mM TMAO (but not glycine) protected both ligand binding and protein stability against pressure. To test TMAO in living cells, we grew yeast under pressure. After 1 h at 71 MPa, 3.5 h at 71 MPa, and 17 h at 30 MPa, 150 mM TMAO generally doubled the number of cells that formed colonies. Sulfur-based osmolytes which are not correlated with depth, such as hypotaurine and thiotaurine, are probably involved in sulfide metabolism and detoxification. Thus deep-sea osmolytes may have at least two other roles beyond acting as simple compatible osmotica.

Comparative Biochemistry and Physiology Part C: Comparative Pharmacology, Nov 1, 1992

The mammalian renal medulla uses sorbitol, myo-jnositol, betaine and gIycerophosphorylcholine as ... more The mammalian renal medulla uses sorbitol, myo-jnositol, betaine and gIycerophosphorylcholine as intracellular osmotytes. 2. Sorbitol synthesis was inhibited by feeding male Wistar rats the aldose reductase inhibitor sorbinil at 40 mg/kg/day for 71 d, and renal inner medullas were extracted for analysis. 3. Aldose reductase activities and sorbitol contents were greatly reduced in sorbinil-treated animals, while betaine contents increased significantly (with no other osmolytes changing). 4. The betaine increase compensated for the sorbitol decrease such that the total organic osmolytes maintained the same ratio to sodium contents as controls. 5. These results are identical to the pattern previously reported for sorbinil treatment of rats for 10 d, but not for 21 d.

PubMed, Jun 1, 2004

Most shallow teleosts have low organic osmolyte contents, e.g. 70 mmol/kg or less of trimethylami... more Most shallow teleosts have low organic osmolyte contents, e.g. 70 mmol/kg or less of trimethylamine oxide (TMAO). Our previous work showed that TMAO contents increase with depth in muscles of several Pacific families of teleost fishes, to about 180 mmol/kg wet wt at 2.9 km depth in grenadiers. We now report that abyssal grenadiers (Coryphaenoides armatus, Macrouridae) from the Atlantic at 4.8 km depth contain 261 mmol/kg wet wt in muscle tissue. This precisely fits a linear trend extrapolated from the earlier data. We also found that anemones show a trend of increasing contents of methylamines (TMAO, betaine) and scyllo-inositol with increasing depth. Previously we found that TMAO counteracts the inhibitory effects of hydrostatic pressure on a variety of proteins. We now report that TMAO and, to a lesser extent, betaine, are generally better stabilizers than other common osmolytes (myo-inositol, taurine and glycine), in terms of counteracting the effects of pressure on NADH Km of grenadier lactate dehydrogenase and ADP Km of anemone and rabbit pyruvate kinase.

Biochimica Et Biophysica Acta - General Subjects, Jun 1, 1987

Temperature effects on dissociation constants (Kd), binding enthalpies and apparent Michaelis con... more Temperature effects on dissociation constants (Kd), binding enthalpies and apparent Michaelis constants (Km) for NADH, plus Arrhenius activation energies (Ea), substrate turnover numbers (kcat), and NADH &#39;on&#39; constants (k1) were measured or calculated for M4-lactate dehydrogenase homologs from deep-sea, midwater, shallow-water temperate, and shallow-water tropical teleost fishes, and a mammal. At any single measurement temperature, Km and kcat values were significantly higher for groups adapted to lower temperatures. This pattern of Km values and temperature illustrates a strong evolutionary conservation of Km of NADH. When determined at the average body temperature of each species, the Km values are very similar, resulting in the preservation of the catalytic capacity and regulatory properties of these enzyme homologs at their in situ temperatures. In contrast, Kd values, while varying considerably among species, are not significantly different among the different groups at any one temperature. The ratio of Km to Kd tends to follow a phylogenetic pattern rather than a pattern of environmental adaptation. Thus, evolutionary adjustments in Km are not directly the result of changes in cofactor binding. All the rate constants involved in determining the Km and Kd of NADH (kcat, k1 and k-1) can be modified.

American Journal of Physiology-renal Physiology, May 1, 1989

A simple high performance liquid chromatography (HPLC) method of separating and quantitating the ... more A simple high performance liquid chromatography (HPLC) method of separating and quantitating the predominant organic solutes of the renal medulla is described. These organic solutes include myo-inositol, glycerophosphorylcholine, sorbitol, betaine, and urea. Other physiologically significant solutes, including glucose and mannitol, can be separated and quantitated concurrently with this method. With the use of this technique, the organic solutes of the rabbit kidney were determined. No new organic compounds were detected by HPLC that could significantly contribute to intracellular osmolality of the medulla. The values for the organic solutes already described were similar to those obtained by more complicated and limited approaches such as classical enzymatic techniques, ion electrodes, nuclear magnetic resonance spectroscopy, and gas chromatography-mass spectroscopy.

American zoologist, Aug 1, 2001

SYNOPSIS. Organic osmolytes are small solutes used by cells of numerous waterstressed organisms a... more SYNOPSIS. Organic osmolytes are small solutes used by cells of numerous waterstressed organisms and tissues to maintain cell volume. All known osmolytes are amino acids and derivatives, polyols and sugars, methylamines, and urea; unlike salt ions, most are ''compatible,'' i.e., do not perturb macromolecules. In addition, some stabilize macromolecules and are ''counteracting'' towards perturbants, e.g., methylamines can stabilize proteins and ligand binding against perturbations by urea in elasmobranchs and mammalian kidney, and (our latest findings) high hydrostatic pressure in deep-sea animals. Methylamines appear to coordinate water molecules tightly, resulting in osmolyte exclusion from hydration layers of peptide backbones. This makes unfolded protein conformations entropically unfavorable (work of Timasheff, Galinski, Bolen and coworkers). These properties have led to proposed uses in biotechnology, agriculture and medicine, including improved biochemical methods, in vitro rescue of misfolded proteins in cystic fibrosis and prion diseases (work of Welch and others), and plants engineered for drought and salt tolerance. These properties also explain some but not all of the considerable variation in osmolyte composition among species with different metabolisms and habitats, and among and within mammalian tissues in development.

Biological and Chemical Oceanography Data Management Office, Mar 18, 2019

Dataset: HADES-K Sediment Meiofaunal DiversityThis dataset includes raw counts of meiofauna ident... more Dataset: HADES-K Sediment Meiofaunal DiversityThis dataset includes raw counts of meiofauna identified in push core samples taken in the Kermadec Trench in the Southwest Pacific, 4000 to ~10,000m from the RV/ Thomas G. Thompson during cruise TN309 (HADES-K), May 2014. For a complete list of measurements, refer to the full dataset description in the supplemental file 'Dataset_description.pdf'. The most current version of this dataset is available at: https://www.bco-dmo.org/dataset/763758NSF Division of Ocean Sciences (NSF OCE) OCE-113162

Kidney International, Aug 1, 1995

Time-dependent aspects of osmolyte changes in rat kidney, urine, blood and lens with sorbinil and... more Time-dependent aspects of osmolyte changes in rat kidney, urine, blood and lens with sorbinil and galactose feeding. Sorbitol plus myo-inositol, betame and glycerophosphorylcholine (GPC) are cellular osmolytes in the mammalian renal medulla. Galactosemia and hyperglycemia can cause excessive levels of galactitol or sorbitol in several organs via aldose reductase (AR) catalysis. AIR inhibitors can reduce these polyols. To examine osmolyte responses to polyol perturbations, male Wistar rats were fed normal diet, the AR inhibitor sorbinil (at 40 mg/kg/d), 25% galactose, or a combination, for 10, 21 and 42 days. All animals at 21 days had higher apparent renal AR activity than at 10 or 42 days, possibly providing resistance to sorbinil. Sorbinil feeding alone tended to increase urinary, plasma and renal urea levels. It reduced AR activity and sorbitol contents in renal inner medulla, though less so at 21 days; other renal osmolytes, especially betaine, were elevated. Galactose feeding caused little change in renal AR activity, and resulted in high galactose and galactitol contents in renal medulla, urine, blood and lens (and higher renal Na contents at 10 days). Renal sorbitol, inositol and GPC decreased, while betaine contents trended higher at all times. Sorbinilgalactose feeding reduced renal AR activities and galactitol contents (again less so at 21 days), urine, blood and lens galactitol, and further reduced renal sorbitol contents. At 10 and 21 days it tended to raise renal betaine more, and restore inositol (but not GPC) contents to control levels. At 42 days it reduced renal and urinary Na and galactose, and decreased renal betaine to control levels. Under most conditions, total renal (non-urea) organic osmolyte contents (presumed to be mostly intracellular) and Na plus galactose contents (presumed mostly extracellular) changed together such that cell volumes may have been maintained. The exception was 10 days on galactose, where total osmolytes appeared too low. In galactose-fed animals, urine/plasma ratios suggest some renal galactitol efflux, and cellular galactitol probably helps maintain osmotic balance rather than cause swelling. Mammalian renal medulla cells must cope with high external salt concentrations produced by the kidney's urine-concentrating mechanism. Like cells of a wide variety of organisms exposed to hypertonicity, renal cells apparently maintain cell volume with "compatible" organic osmolytes, solutes which do not exhibit the disruptive effects on macromolecules that occur with high NaC1 or KC1 [1, 2]. Compatible osmolytes in most organisms are polyols, methylamines, and free amino acids [2]; in the mammalian renal medulla, the major ones are sorbitol, myo-inositol, glycerophos

American Journal of Physiology-renal Physiology, Oct 1, 1992

Renal medullary cells contain high levels of (glycine) betaine, glycerophosphorylcholine (GPC), m... more Renal medullary cells contain high levels of (glycine) betaine, glycerophosphorylcholine (GPC), myo-inositol, and sorbitol. Two functions of these have been proposed: 1) that they are compatible osmolytes which regulate cell volume (against high external NaCl) without inhibiting proteins and 2) that methylamines (GPC and betaine) are counteracting osmolytes which stabilize proteins against perturbation from high renal urea. As a test of the latter, osmolyte contents in kidney medullas were measured in rats subjected to three types of dietary manipulation: 1) diets with protein and NaCl contents varied oppositely, 2) diets with a constant low NaCl and varied protein content, and 3) a low-calorie diet. With low-protein and low-calorie diets, only renal contents of urea, GPC, and inositol decreased; betaine and sorbitol contents increased such that contents of total nonurea organic osmolytes remained constant. With high-protein diets, only renal contents of sodium, urea, and GPC increased, with the latter giving total organic osmolytes a consistent correlation to sodium. Across all diets, the only consistent (linear) correlations were 1) between urea and GPC contents, supporting previous suggestions that GPC is the major counteractant to urea, and 2) between total organic osmolytes and sodium (but not urea) contents, as predicted by the compatible osmolytes hypothesis.

American zoologist, Aug 1, 2001

SYNOPSIS. Organic osmolytes are small solutes used by cells of numerous waterstressed organisms a... more SYNOPSIS. Organic osmolytes are small solutes used by cells of numerous waterstressed organisms and tissues to maintain cell volume. All known osmolytes are amino acids and derivatives, polyols and sugars, methylamines, and urea; unlike salt ions, most are ''compatible,'' i.e., do not perturb macromolecules. In addition, some stabilize macromolecules and are ''counteracting'' towards perturbants, e.g., methylamines can stabilize proteins and ligand binding against perturbations by urea in elasmobranchs and mammalian kidney, and (our latest findings) high hydrostatic pressure in deep-sea animals. Methylamines appear to coordinate water molecules tightly, resulting in osmolyte exclusion from hydration layers of peptide backbones. This makes unfolded protein conformations entropically unfavorable (work of Timasheff, Galinski, Bolen and coworkers). These properties have led to proposed uses in biotechnology, agriculture and medicine, including improved biochemical methods, in vitro rescue of misfolded proteins in cystic fibrosis and prion diseases (work of Welch and others), and plants engineered for drought and salt tolerance. These properties also explain some but not all of the considerable variation in osmolyte composition among species with different metabolisms and habitats, and among and within mammalian tissues in development.

Typical mammalian body fluids have osmotic pressures of about 300 mosm/kg, with inorganic ions as... more Typical mammalian body fluids have osmotic pressures of about 300 mosm/kg, with inorganic ions as the major osmotic effectors (osmolytes) both extra- and intracellularly. Many non-mammalian species face much higher osmotic pressures, and comparative physiologists have long known that cells in such organisms generally use organic solutes to maintain osmotic balance. From eubacteria to lower vertebrates, these organic osmolytes appear to fall within a few categories of compounds, namely polyols, neutral amino acids and derivatives, dimethyl-sulfonioproprionate, and urea, usually in combination with methylamines (Yancey et al. 1982; Somero, this Vol.). Only recently has it been fully recognized that some mammalian tissues follow this widespread evolutionary pattern, in particular the kidney. As a consequence of the urine-concentrating mechanism, cells of the renal inner medulla may be exposed to extracellular urea and NaC1 at well over 1000 mosm/kg. In the mid-1980s (Balaban and Knepper 1983; Finely 1984; Bagnasco et al. 1986), it was found that the inner kidney can contain high levels of the polyols sorbitol and (myo)-inositol, and the methylamines betaine and glycerophosphorylcholine (GPC; first detected by Ullrich 1959). These appear to be intracellular (since they are not found in urine or blood), and it was proposed that these compounds serve as osmolytes in renal cell volume maintenance (Fig. 1).

The journal of college science teaching, 1992

Physiological and Biochemical Zoology, 2010