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1. Независимое

   Gadsby DC. Ion channels versus ion pumps: the principal difference, in principle Nature Reviews Molecular Cell Biology, 2009.

   doi:10.1038/nrm2668PubMed 19339978

   Финансирование и результат

   Финансирование

   NIH grants HL36783, HL49907 and DK51767.

   Результат

   Review. Each Na,K-ATPase pump exports 3 Na+ and imports 2 K+ for each ATP hydrolysed and can repeat this cycle up to a hundred times a second; the net charge movement generates a current of about 20 attoamperes per pump.

2. Справочное издание

   UniProt Consortium. UniProt: the Universal Protein Knowledgebase in 2025 Nucleic Acids Research, 2025.

   doi:10.1093/nar/gkae1010PubMed 39552041

   Финансирование и результат

   Финансирование

   National Human Genome Research Institute (NHGRI) [HG002273]; Office of the Director, NIH OD [U24HG007822]; NIAID; NIA; NIGMS [R35GM141873]; NIDDK; NEI; NCI; NHLBI; Biotechnology and Biological Sciences Research Council (BBSRC) [BB/T015608/1]; National Science Foundation's Directorate for Biological Sciences [BB/X002179/1]; Open Targets; Horizon 2020 [825575]; State Secretariat for Education, Research and Innovation (SERI); EMBL Australia. Funding for open access charge: National Institutes of Health.

   Результат

   Reviewed human UniProtKB entries, release 2026_03, read through rest.uniprot.org on 2026-10-21. SLC5A1 (P13866, SGLT1): electrogenic Na+-coupled symporter of D-glucose or D-galactose with a Na+ to sugar coupling ratio of 2:1, driven by the transmembrane Na+ electrochemical gradient set by the Na+/K+ pump; absorbs the sugars across the apical brush-border membrane of enterocytes, with basolateral exit through GLUT2. ATP1A1 (P05023): catalytic subunit of the Na+/K+-ATPase, which hydrolyses ATP to export 3 Na+ and import 2 K+ per cycle against their electrochemical gradients; the pump comprises a catalytic alpha, an auxiliary beta and a regulatory FXYD subunit, with four, three and seven isoforms respectively; active site Asp376 forms the 4-aspartylphosphate intermediate; the inward-facing E1 state binds three Na+ from the cytoplasm and is phosphorylated at the active-site Asp, and in the outward-facing E2 state Na+ is released outside, two K+ bind, and dephosphorylation restores the inward-facing state, releasing K+ into the cytoplasm. ATP6V1A (P38606): catalytic subunit of the V1 complex of the vacuolar H+-ATPase, which acidifies and maintains the pH of intracellular compartments; located in the lysosome membrane among other sites. FOXO1 (Q12778): transcription factor that is the main target of insulin signalling; modified-residue features Thr-24 phosphorylated by PKB/AKT1 or PKB/AKT2 and SGK1, Ser-256 by PKB/AKT1 and SGK1, Ser-319 by PKB/AKT1; AKT1 phosphorylation promotes nuclear export and inactivation; in hepatocytes, by similarity, it acts with PPARGC1A and CEBPA to activate expression of genes such as IGFBP1, G6PC1 and PCK1.

3. Независимое

   Palmer LG, Schnermann J. Integrated control of Na transport along the nephron Clinical Journal of the American Society of Nephrology, 2015.

   doi:10.2215/CJN.12391213PubMed 25098598

   Финансирование и результат

   Финансирование

   L.G. Palmer: National Institutes of Health grant R01-DK27847. J. Schnermann: Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases.

   Результат

   Review. More than 500 g of sodium is filtered daily; under most conditions the kidneys excrete more than 95% of ingested sodium. The proximal tubule reabsorbs 60-70% (apical NHE3 the main mechanism), the ascending loop of Henle, mostly the thick limb, 25-30% (NKCC2 and NHE3), and the distal convoluted tubule and collecting ducts no more than 5-10%, through thiazide-sensitive NCC (early DCT) and amiloride-sensitive ENaC (late DCT, connecting tubule, collecting duct); distal reabsorption is the regulated part. Two-thirds or more of renal oxygen uptake is spent on the Na,K-ATPase. With plausible tenfold changes in intake, fractional reabsorption varies between about 97% and 99.7%. Sodium depletion increases ENaC activity, an effect mimicked by aldosterone. Potassium loading lowers NCC phosphorylation and abundance and raises ENaC activity, shifting sodium reabsorption to segments where principal cells secrete K+ in exchange for Na+. Changes in body Na content and blood volume are the likely cause of the relation between Na intake and blood pressure.

4. Справочное издание

   Milo R, Phillips R. Cell Biology by the Numbers Garland Science, 2015.

   doi:10.1201/9780429258770

   Финансирование и результат

   Финансирование

   not stated

   Результат

   Textbook, online edition read 2026-10-21 at book.bionumbers.org. Vignette 'What are the concentrations of different ions in cells?': in mammalian cells potassium is the dominant positive ion, at more than 10-fold the concentration of sodium, and outside the cell sodium dominates; potassium, about 10 to 30-fold more concentrated inside than outside, is usually close to electrochemical equilibrium in animal cells: its outward diffusion creates a potential difference that grows until it balances the diffusive flux, leaving the cell interior negative; in the extreme case of calcium the concentration outside is 10,000-fold that inside. Vignette 'What is the power consumption of a cell?', Table 1, adapted from Rolfe and Brown, Physiological Reviews 1997, rounded to one significant digit, with tissues described as rat ('rate tissues') in the caption and mouse in the text: share of the Na+/K+-ATPase in the oxygen consumption of tissues in the standard state, liver 5-10%, kidney 40-70%, heart 1-5%, brain 50-60%, skeletal muscle 5-10%.

5. Независимое

   Abdul Kadir L, Stacey M, Barrett-Jolley R. Emerging Roles of the Membrane Potential: Action Beyond the Action Potential Frontiers in Physiology, 2018.

   doi:10.3389/fphys.2018.01661PubMed 30519193

   Финансирование и результат

   Финансирование

   RB-J is currently a holder of BBSRC funding (BB/N003020/1).

   Результат

   Review. The resting membrane potential is maintained by the differential permeability of the plasma membrane to ions and by the cell's complement of ion channels, and is typically in the range of -10 to -100 mV. In pancreatic beta cells, rising blood glucose increases ATP and decreases ADP, which closes ATP-sensitive K+ channels; the membrane depolarises, Ca2+ enters and insulin is released.

6. Справочное издание

   Ragueneau E, Gong C, Sinquin P, Sevilla C, Beavers D, Grentner A, et al. The Reactome Knowledgebase 2026 Nucleic Acids Research, 2026.

   doi:10.1093/nar/gkaf1223PubMed 41251150

   Финансирование и результат

   Финансирование

   The development of Reactome is supported by grants from the National Institutes of Health (U24HG012198 and U24HG012198-02S1 for Core Trust Seal development; U24HG011851), European Bioinformatics Institute (EMBL-EBI), Open Targets (The Target Validation Platform), and Connected Minds Prototyping (York University). Funding to pay the Open Access publication charges for this article was provided by the National Institutes of Health (U24HG012198). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

   Результат

   Expert-curated knowledgebase of human pathways; pathway summaries of release 97 read through reactome.org/ContentService on 2026-10-21. Glycolysis (R-HSA-70171): the entire process is cytosolic. Pentose phosphate pathway (R-HSA-71336, cytosol): generates a substantial fraction of the cytoplasmic NADPH and ribose 5-phosphate for nucleotide synthesis. Citric acid cycle (R-HSA-71403): all reactions take place in the mitochondrion. Mitochondrial fatty acid beta-oxidation (R-HSA-77289): in the mitochondrial matrix after import by carnitine acyltransferases. Respiratory electron transport (R-HSA-611105): located in the inner mitochondrial membrane; the proton electrochemical gradient across it drives ATP synthase. SRP-dependent cotranslational protein targeting to membrane (R-HSA-1799339): the signal recognition particle binds the signal sequence of a nascent polypeptide and docks the ribosome complex with the SRP receptor on the ER membrane, where it passes to the translocon. Lysosome vesicle biogenesis (R-HSA-432720): the secretory pathway carries secreted proteins, resident proteins of the ER, Golgi and lysosomes and integral membrane proteins. Asparagine N-linked glycosylation (R-HSA-446203) and LLO biosynthesis (R-HSA-446193): N-glycans derive from a 14-sugar dolichol-linked precursor synthesised in the ER and are further modified in the Golgi compartments. Glycosphingolipid catabolism (R-HSA-9840310) and autophagy (R-HSA-9612973): endocytosed gangliosides and autophagic cargo are degraded in lysosomes; lack of an enzyme or cofactor causes sphingolipidoses including Gaucher and Niemann-Pick diseases. Peroxisomal lipid metabolism (R-HSA-390918), beta-oxidation of very long chain fatty acids (R-HSA-390247) and plasmalogen biosynthesis (R-HSA-75896): peroxisomal enzymes catabolise phytanate, pristanate and very-long-chain fatty acids and catalyse the first four steps of plasmalogen synthesis. mRNA splicing (R-HSA-72163, nucleoplasm) and transport of mature transcript to cytoplasm (R-HSA-72202): pre-mRNAs are capped, polyadenylated and spliced and processed mRNA is exported through the nuclear pore complex. Urea cycle (R-HSA-70635): carbamoyl phosphate is synthesised in mitochondria and cytosolic ARG1 is the canonical arginase. Gluconeogenesis (R-HSA-70263): converts mitochondrial pyruvate to cytosolic glucose 6-phosphate. PIP3 activates AKT signaling (R-HSA-1257604): PI3K converts PIP2 to PIP3, which recruits AKT to the plasma membrane, where TORC2 phosphorylates a serine and PDPK1 a threonine of AKT.

7. Справочное издание

   Chinnery PF. Primary Mitochondrial Disorders Overview GeneReviews, University of Washington, Seattle, 2021.

   PubMed 20301403

   Финансирование и результат

   Финансирование

   not stated in the chapter

   Результат

   Expert-authored, peer-reviewed overview, posted 8 June 2000, comprehensive update 29 July 2021. More than 70 polypeptides form the respiratory chain on the inner mitochondrial membrane. Mitochondrial DNA encodes 13 essential respiratory-chain subunits (seven of complex I, one of complex III, three of complex IV and two of complex V), two ribosomal RNAs (12S and 16S) and 22 transfer RNAs for intra-mitochondrial protein synthesis; the remaining respiratory-chain polypeptides and the proteins for respiratory-chain assembly, mitochondrial structure and mtDNA maintenance and expression are encoded by the nuclear genome. Each human cell contains thousands of copies of mtDNA; in heteroplasmy, mutated and wild-type mtDNA coexist, and the proportion of mutated mtDNA must exceed a critical threshold before a cell expresses a biochemical defect of the respiratory chain. mtDNA pathogenic variants are transmitted by maternal inheritance; offspring of males with an mtDNA pathogenic variant do not inherit it.

8. Независимое

   Teschke R. Alcoholic liver disease: alcohol metabolism, cascade of molecular mechanisms, cellular targets, and clinical aspects Biomedicines, 2018.

   doi:10.3390/biomedicines6040106PubMed 30424581

   Финансирование и результат

   Финансирование

   There was no funding of this article.

   Результат

   Narrative review. In the liver, ADH (cytosol, NAD+), the microsomal ethanol-oxidizing system with CYP2E1 (endoplasmic reticulum, NADPH and O2) and catalase (peroxisomes, H2O2) oxidise ethanol to acetaldehyde; ADH and MEOS, but not catalase, are relevant in vivo. Km for ethanol: ADH 0.5 to 2.0 mM (animal studies), MEOS 7 to 11 mM, catalase 0.6 to 10 mM. MEOS is induced by chronic alcohol consumption through increased CYP2E1 synthesis. Mitochondrial ALDH oxidises acetaldehyde to acetate, which is released into the blood and oxidised in extrahepatic tissues; ADH and ALDH both generate NADH. The raised NADH/NAD+ ratio stimulates hepatic fatty acid synthesis and alpha-glycerophosphate supply, and acetaldehyde impairs mitochondrial fatty acid oxidation.

9. Справочное издание

   Erdem F, Canda E. GNPTAB-Related Disorders GeneReviews, University of Washington, Seattle, 2026.

   PubMed 20301728

   Финансирование и результат

   Финансирование

   not stated in the chapter

   Результат

   Expert-authored, peer-reviewed chapter, first posted 2008, comprehensive update 13 August 2026. GNPTAB encodes the alpha and beta subunits of N-acetylglucosamine-1-phosphotransferase, which synthesises the mannose 6-phosphate recognition marker that sorts newly synthesised lysosomal enzymes from the Golgi apparatus to lysosomes; the p.Lys4Gln variant impairs retention of the enzyme in the Golgi complex. Defective enzyme causes mis-sorting of lysosomal enzymes and accumulation of nondegradable macromolecules in lysosomes; complete loss of activity gives mucolipidosis II alpha/beta and residual activity of 1-10% usually mucolipidosis III alpha/beta.

10. Справочное издание

    Steinberg SJ, Raymond GV, Braverman NE, Moser AB. Zellweger Spectrum Disorder GeneReviews, University of Washington, Seattle, 2020.

    PubMed 20301621

    Финансирование и результат

    Финансирование

    not stated in the chapter

    Результат

    Expert-authored, peer-reviewed chapter, first posted 2003, comprehensive update 29 October 2020. Biallelic pathogenic variants in any one of 13 PEX genes, which encode peroxins required for peroxisome membrane biogenesis, division and matrix protein import, cause Zellweger spectrum disorder. Screening findings include raised plasma C26:0 and C26:1 and C24/C22 and C26/C22 ratios, raised phytanic and pristanic acid, reduced erythrocyte C16 and C18 plasmalogens, raised pipecolic acid and raised C27 bile acid intermediates. About 15% of individuals with a ZSD-like phenotype and raised plasma VLCFA have a single-enzyme deficiency of peroxisomal beta-oxidation (D-bifunctional enzyme or acyl-CoA oxidase).

11. Независимое

    Petersen MC, Shulman GI. Mechanisms of insulin action and insulin resistance Physiological Reviews, 2018.

    doi:10.1152/physrev.00063.2017PubMed 30067154

    Финансирование и результат

    Финансирование

    M. C. Petersen is supported by National Institutes of Health (NIH) Medical Scientist Training Program Grant T32 GM-007205 and National Research Service Award F30 DK-104596. G. I. Shulman is supported by NIH Grants R01 DK116774, R01 DK113984, R01 DK114793, and P30 DK-45735.

    Результат

    Narrative review. INSR is a heterotetramer of two insulin-binding alpha subunits and two beta subunits with tyrosine kinase domains; trans-autophosphorylation of Tyr1162, Tyr1158 and Tyr1163 activates it, and it phosphorylates IRS1 and IRS2, which recruit PI3K (p85 regulatory, p110 catalytic). PIP3 recruits PDK1 and AKT, phosphorylated at Thr308 by PDK1 and at Ser473 by mTORC2. In primary human myotubes, knockdown of AKT2 but not AKT1 abrogated insulin-stimulated glucose uptake and glycogen synthesis; a partial loss-of-function AKT2 variant in about 1% of the Finnish population impairs insulin-stimulated glucose uptake and increases endogenous glucose production. AKT phosphorylation of TBC1D4 (AS160) blocks its inactivation of Rab GTPases and promotes GLUT4 storage-vesicle translocation, first reported in 1980; a truncating TBC1D4 mutation caused profound insulin resistance in one family. Glycogen synthesis accounts for about 75% of insulin-stimulated glucose disposal in human muscle; mice with GSK3 insensitive to insulin have normal insulin-stimulated glycogen synthesis, suggesting acute control mainly by glucose 6-phosphate allostery. Muscle stores energy mostly for its own use, releasing lactate and alanine. Hepatocyte glucose transport is not insulin-regulated; AKT phosphorylates FOXO1, excluding it from the nucleus and lowering G6pc and Pck1 transcription. Suppression of adipose lipolysis has an ED50 of about 20 µU/mL insulin, within a physiological range of about 5 to 60 µU/mL. Hepatic glycogen is nearly depleted after 48 h of fasting in humans, while gluconeogenic flux stays relatively constant for about 48 h. In rodents, acute insulin suppression of gluconeogenesis depends mainly on suppression of adipose lipolysis, hepatic acetyl-CoA and pyruvate carboxylase flux, and mice lacking hepatic AKT1, AKT2 and FOXO1 suppressed glucose production normally; the quantitative significance in humans remains to be explored. Insulin suppresses glucagon secretion through paracrine action in the islet.

12. Независимое

    Petersen MC, Vatner DF, Shulman GI. Regulation of hepatic glucose metabolism in health and disease Nature Reviews Endocrinology, 2017.

    doi:10.1038/nrendo.2017.80PubMed 28731034

    Финансирование и результат

    Финансирование

    M.C.P. acknowledges grant support from the US National Institutes of Health (NIH; grants F30 DK-104596 and T32 GM-007205). D.F.V. acknowledges grant support from the NIH (grant K23 DK-102874). G.I.S. acknowledges grant support from the NIH (grants R01 DK40936, R01 DK113984 and P30 DK045735).

    Результат

    Narrative review. Glucagon receptor (GCGR) activation raises cAMP and activates PKA, which inhibits L-type pyruvate kinase, phosphorylates PFK-2/FBPase-2 to favour its phosphatase activity and lower fructose 2,6-bisphosphate, an allosteric inhibitor of FBPase-1 (printed as fructose-2,6-bisphosphatase 1), phosphorylates and inactivates glycogen synthase, and activates phosphorylase kinase, which phosphorylates glycogen phosphorylase at Ser15; PKA also activates the CREB-CBP-CRTC2 complex for gluconeogenic gene transcription. FOXO proteins with PGC1-alpha raise PCK1 and G6PC expression and are excluded from the nucleus after AKT phosphorylation. Glucose enters hepatocytes by facilitated diffusion through GLUT2; glucose allosterically inhibits glycogen phosphorylase; glucose 6-phosphate is the key allosteric activator of GYS2. In overnight-fasted humans under somatostatin, hyperinsulinaemia was required to stimulate hepatic glycogen synthesis and hyperglycaemia to suppress glycogenolysis. Hepatic glucose production and storage are dysregulated in type 1 and type 2 diabetes mellitus, and this imbalance contributes to hyperglycaemia in the fasted and postprandial states. Metformin is used as first-line therapy for type 2 diabetes and acts primarily through the suppression of hepatic gluconeogenesis, by a molecular mechanism that remains under investigation. Several lines of evidence cast doubt on the necessity of AMPK: metformin continues to inhibit glucose production in Ampk-knockout primary mouse hepatocytes and improves glucose tolerance in Ampk-knockout mice to a similar extent as in wild-type mice. Inhibition of mitochondrial complex I is observed only at suprapharmacological, millimolar concentrations, in contrast to the clinically relevant plasma concentration range of 50 to 100 µM in patients who take 2 g of metformin daily. Metformin non-competitively inhibits mitochondrial glycerol-3-phosphate dehydrogenase in isolated hepatocytes with a clinically relevant Ki of about 50 µM, which predicts impaired gluconeogenesis only from the redox-dependent substrates lactate and glycerol and not from pyruvate, alanine or dihydroxyacetone phosphate; the importance of the glycerol-3-phosphate shuttle in gluconeogenesis in the human liver is unclear, so studies in humans are required.

13. Финансирование не установлено

    Rolfe DF, Brown GC. Cellular energy utilization and molecular origin of standard metabolic rate in mammals Physiological Reviews, 1997.

    doi:10.1152/physrev.1997.77.3.731PubMed 9234964

    Финансирование и результат

    Финансирование

    Not read: the publisher's HTML and PDF full text returned HTTP 403 on 2026-10-21; the PubMed, Europe PMC and Crossref records list no funder, and Semantic Scholar lists no open-access copy.

    Результат

    Review with quantitative estimates for mammals in the standard state, read in the abstract. About 90% of oxygen consumption is mitochondrial, of which about 20% is uncoupled by the mitochondrial proton leak and 80% is coupled to ATP synthesis. Of the 80% coupled to ATP synthesis, about 25-30% is used by protein synthesis, 19-28% by the Na+-K+-ATPase, 4-8% by the Ca2+-ATPase, 2-8% by the actinomyosin ATPase, 7-10% by gluconeogenesis and 3% by ureagenesis.