{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LDHAL6B is a member of the lactate dehydrogenase (LDH) gene family that catalyzes the reversible conversion of pyruvate to lactate using NADH/NAD⁺ as a cofactor—a reaction central to anaerobic glycolysis and overall cellular energy metabolism. Structural and kinetic studies have demonstrated that conserved catalytic domains mediate efficient substrate and coenzyme binding, thereby ensuring proper control of metabolic flux under diverse physiological conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its canonical metabolic role, LDHAL6B is subject to tight regulation at both the transcriptional and post‐translational levels. Hormonal stimuli and cellular stressors can modulate its expression and activity to adapt energy production and maintain redox balance. In addition, interactions with molecular chaperones have been shown to prevent aberrant protein aggregation under conditions of thermal or chemical stress, thereby preserving enzyme function in critical contexts such as cardiac and neuronal tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, alterations in LDH family members play key roles in pathological states—ranging from myocardial infarction to neurodegeneration—by reflecting shifts in metabolic equilibrium and cellular injury. The enzyme’s dynamic regulation by cyclic AMP and other signaling molecules in tissue-specific settings underscores its extra‐metabolic roles in coordinating stress adaptations and cell survival responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, LDHAL6B functions not only as a pivotal enzyme in regulating the balance between lactate and pyruvate during energy metabolism but also serves as an adaptable metabolic sensor. Its regulated activity helps tailor cellular energy production to meet the fluctuating demands of different tissues and pathological conditions, making it a potential marker and target in metabolic and degenerative diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "S S Taylor, S S Oxley, W S Allison, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Aminoacid sequence of dogfish M4 lactate dehydrogenase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (1973)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.70.6.1790"}], "href": "https://doi.org/10.1073/pnas.70.6.1790"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "4515938"}], "href": "https://pubmed.ncbi.nlm.nih.gov/4515938"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "M J Adams, M Buehner, K Chandrasekhar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure-function relationships in lactate dehydrogenase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (1973)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.70.7.1968"}], "href": "https://doi.org/10.1073/pnas.70.7.1968"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "4146647"}], "href": "https://pubmed.ncbi.nlm.nih.gov/4146647"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "R D Meyer, F A McMorris "}, {"type": "b", "children": [{"type": "t", "text": "Induction of both rat and mouse lactate dehydrogenase in hybrids between inducible rat glioma and uninducible mouse neuroblastoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (1980)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.1041030102"}], "href": "https://doi.org/10.1002/jcp.1041030102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "6253503"}], "href": "https://pubmed.ncbi.nlm.nih.gov/6253503"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "E Goldberg "}, {"type": "b", "children": [{"type": "t", "text": "Immunochemical specificity of lactate dehydrogenase-X."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (1971)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.68.2.349"}], "href": "https://doi.org/10.1073/pnas.68.2.349"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "5277084"}], "href": "https://pubmed.ncbi.nlm.nih.gov/5277084"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Rui Tian, Sheng-Jian Li, Dong-Liang Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The acidic C-terminal domain stabilizes the chaperone function of protein disulfide isomerase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M407076200"}], "href": "https://doi.org/10.1074/jbc.M407076200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15358778"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15358778"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Rui Tian, Chun-Lai Nie, Rong-Qiao He "}, {"type": "b", "children": [{"type": "t", "text": "Chaperone-like manner of human neuronal tau towards lactate dehydrogenase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurochem Res (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1023/b:nere.0000042213.68600.65"}], "href": "https://doi.org/10.1023/b:nere.0000042213.68600.65"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15532542"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15532542"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "D A Smith, F Y Leung, G Jablonsky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Determination, by radioimmunoassay, of the mass of lactate dehydrogenase isoenzyme 1 in human serum and of its rate of removal from serum after a myocardial infarction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Chem (1987)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "3665041"}], "href": "https://pubmed.ncbi.nlm.nih.gov/3665041"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "M Machida, H Matsuzawa, T Ohta "}, {"type": "b", "children": [{"type": "t", "text": "Fructose 1,6-bisphosphate-dependent L-lactate dehydrogenase from Thermus aquaticus YT-1, an extreme thermophile: activation by citrate and modification reagents and comparison with Thermus caldophilus GK24 L-lactate dehydrogenase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biochem (1985)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/oxfordjournals.jbchem.a135132"}], "href": "https://doi.org/10.1093/oxfordjournals.jbchem.a135132"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "4019440"}], "href": "https://pubmed.ncbi.nlm.nih.gov/4019440"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "C Y Lee, R D Eichner, N O Kaplan "}, {"type": "b", "children": [{"type": "t", "text": "Conformations of diphosphopyridine coenzymes upon binding to dehydrogenases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (1973)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.70.5.1593"}], "href": "https://doi.org/10.1073/pnas.70.5.1593"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "4351183"}], "href": "https://pubmed.ncbi.nlm.nih.gov/4351183"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "D F Derda, M F Miles, J S Schweppe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cyclic AMP regulation of lactate dehydrogenase. Isoproterenol and N6,O2'-dibutyryl cyclic AMP increase the levels of lactate dehydrogenase-5 isozyme and its messenger RNA in rat C6 glioma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (1980)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "6160145"}], "href": "https://pubmed.ncbi.nlm.nih.gov/6160145"}]}]}]}