Leucine-rich repeats containing 4 ( LRRC4 , also named netrin-G ligand 2 [NGL-2]) is a member of the NetrinGs ligands (NGLs) family. As a gene with relatively high and specific expression in brain, it is a member of the leucine-rich repeat superfamily and has been proven to be a suppressor gene for gliomas, thus being involved in gliomagenesis. LRRC4 is the core of microRNA-dependent multi-phase regulatory loops that inhibit the proliferation and invasion of glioblastoma (GB) cells, including LRRC4/NGL2-activator protein 2 (AP2)-microRNA (miR) 182-LRRC4 and LRRC4-miR185-DNA methyltransferase 1 (DNMT1)-LRRC4/specific protein 1 (SP1)-DNMT1-LRRC4. In this review, we demonstrated LRRC4 as a new member of the partitioning-defective protein (PAR) polarity complex that promotes axon differentiation, mediates the formation and plasticity of synapses, and assists information input to the hippocampus and storage of memory. As an important synapse regulator, aberrant expression of LRRC4 has been detected in autism, spinal injury and GBs. LRRC4 is a candidate susceptibility gene for autism and a neuro-protective factor in spinal nerve damage. In GBs, LRRC4 is a novel inhibitor of autophagy, and an inhibitor of protein-protein interactions involving in temozolomide resistance, tumor immune microenvironment, and formation of circular RNA.
Humans ; Cell Line, Tumor ; Glioblastoma/metabolism* ; Leucine ; Leucine-Rich Repeat Proteins/genetics* ; MicroRNAs ; Nerve Tissue Proteins/genetics* ; Tumor Microenvironment

In this study, Escherichia coli BL21 (DE3) was used as the host to construct 2 recombinant E. coli strains that co-expressed leucine dehydrogenase (LDH, Bacillus cereus)/formate dehydrogenase (FDH, Ancylobacter aquaticus), or leucine dehydrogenase (LDH, Bacillus cereus)/alcohol dehydrogenase (ADH, Rhodococcus), respectively. L-2-aminobutyric acid was then synthesized by L-threonine deaminase (L-TD) with LDH-FDH or LDH-ADH by coupling with two different NADH regeneration systems. LDH-FDH process and LDH-ADH process were optimized and compared with each other. The optimum reaction pH of LDH-FDH process was 7.5, and the optimum reaction temperature was 35 °C. After 28 h, the concentration of L-2-aminobutyric acid was 161.8 g/L with a yield of 97%, when adding L-threonine in batches for controlling 2-ketobutyric acid concentration less than 15 g/L and using 50 g/L ammonium formate, 0.3 g/L NAD+, 10% LDH-FDH crude enzyme solution (V/V) and 7 500 U/L L-TD. The optimum reaction pH of LDH-ADH process was 8.0, and the optimum reaction temperature was 35 °C. After 24 h, the concentration of L-2-aminobutyric acid was 119.6 g/L with a yield of 98%, when adding L-threonine and isopropanol (1.2 times of L-threonine) in batches for controlling 2-ketobutyric acid concentration less than 15 g/L, removing acetone in time and using 0.3 g/L NAD⁺, 10% LDH-ADH crude enzyme solution (V/V) and 7 500 U/L L-TD. The process and results used in this paper provide a reference for the industrialization of L-2-aminobutyric acid.
Aminobutyrates ; metabolism ; Escherichia coli ; genetics ; Formate Dehydrogenases ; metabolism ; Leucine Dehydrogenase ; metabolism ; NAD ; metabolism

Parkinson's disease (PD) is a multifaceted disease in which environmental variables combined with genetic predisposition cause dopaminergic (DAergic) neuron loss in the substantia nigra pars compacta. The mutation of leucine-rich repeat kinase 2 (Lrrk2) is the most common autosomal dominant mutation in PD, and it has also been reported in sporadic cases. A growing body of research suggests that circadian rhythm disruption, particularly sleep-wake abnormality, is common during the early phase of PD. Our present study aimed to evaluate the impact of sleep deprivation (SD) on motor ability, sleep performance, and PD pathologies in Lrrk2^G2019S transgenic mice. After two months of SD, Lrrk2^G2019S mice at 12 months of age showed an exacerbated PD-like phenotype with motor deficits, a reduced striatal DA level, degenerated DAergic neurons, and altered sleep structure and biological rhythm accompanied by the decreased protein expression level of circadian locomotor output cycles kaput Lrrk2 gene in the brain. All these changes persisted and were even more evident in 18-month-old mice after 6 months of follow-up. Moreover, a significant increase in α-synuclein aggregation was found in SD-treated transgenic mice at 18 months of age. Taken together, our findings indicate that sleep abnormalities, as a risk factor, may contribute to the pathogenesis and progression of PD. Early detection of sleep disorders and improvement of sleep quality may help to delay disease progression and provide long-term clinical benefits.
Animals ; Electroencephalography ; Leucine/genetics* ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics* ; Mice ; Mice, Transgenic ; Mutation ; Parkinson Disease/metabolism* ; Sleep Deprivation/complications* ; alpha-Synuclein/genetics*

Isolated 3-methylcrotonyl-CoA carboxylase deficiency is an autosomal recessive disorder affecting leucine metabolism; it is one of the most common inborn metabolic diseases detected in newborn screening. Mutations in the genes MCCC1 or MCCC2 cause a defect in the enzyme 3-methylcrotonyl-CoA carboxylase, with MCCC2 mutations being the form predominantly reported in Korea. The majority of infants identified by neonatal screening usually appear to be asymptomatic and remain healthy; however, some patients have been reported to exhibit mild to severe metabolic decompensation and neurologic manifestations. Here we report the clinical features of a patient with asymptomatic 3-methylcrotonyl-CoA carboxylase deficiency and novel heterozygous MCCC1 mutations.
Humans ; Infant ; Infant, Newborn ; Korea ; Leucine ; Mass Screening ; Metabolic Diseases ; Metabolism ; Neonatal Screening ; Neurologic Manifestations

3-Methylcrotonyl-CoA carboxylase(MCC) is a biotin-dependent enzyme involved in the leucine metabolism. We describe a patient with MCC deficiency who manifested with Reye syndrome-like illness with status epilepticus, metabolic acidosis, hypoglycemia, hyperammonemia, elevated liver enzymes and neurologic impairments after a viral gastroenteritis and then suffered from Lennox-Gastaut syndrome. Urinary organic acid analysis revealed increased excretions of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine. This patient was managed with a leucine restriction diet and supplementation of biotin and carnitine, which was not so effective. He suffered from neurologic sequelae such as Lennox-Gastaut syndrome, motor and cognitive impairements.
Acidosis ; Biotin ; Carnitine ; Diet ; Gastroenteritis ; Humans ; Hyperammonemia ; Hypoglycemia ; Leucine ; Liver ; Metabolism ; Status Epilepticus

The purpose of this study was to investigate the relationship among calcium intake, blood parameters related with bone metabolism, and serum lipids in healthy adults on self-selected diet. Subjects were consisted of 40 female college students residing in Chungnam. Anthropometric measurements, dietary intake measurements and blood collection were conducted. Serum concentrations of total protein, albumin, alkaline phosphates, leucine amino peptidase, BUN, calcium, inorganic phosphorus, and lipids were measured by biochemical analyzer and ICP spectrometer. The results were as follows. The mean age of subjects was 22.34 years and weight, height and BMI were 52.89kg, 161.29cm and 20.34, respectively. The daily mean energy and calcium intakes were 81.75% and 64.38% of RDA. The mean animal 1:2. The mean serum concentrations were 6.54g/dl(total protein), 4.12g/dl(albumin), 123.24U/iota(alkaline phosphates), 36.59U/iota(leucine amino peptidase), 8.26mg/dl(calcium), 3.29mg/dl(inorganic phosphorus), 60.73mg/dl(triglyceride), 138.49mg/dl(total cholesterol), 65.95mg/dl(HDL-cholesterol), and 60.39mg/dl(LDL-cholesterol). There were no significant differences among calcium intake, bone metabolism parameters, and serum lipids when analyzed by Pearson's correlation coefficient. More systematic studies are required to investigate the roles of calcium in healthy persons on self-selected diets containing different levels of calcium.
Adult ; Animals ; Calcium* ; Chungcheongnam-do* ; Diet ; Female* ; Humans ; Leucine ; Metabolism* ; Phosphates ; Phosphorus

Microcystin-leucine arginine (MC-LR), a potentially carcinogenic toxin, is produced by Cyanobacteria such as Microcystis and Ananabacteria during water bloom. Increasing evidence demonstrated that MC-LR induces male reproductive toxicity, mainly by inducing germ cell apoptosis, destroying cell cytoskeleton, interfering with DNA damage repair pathway, and damaging blood-testicular barrier (BTB), which eventually lead to male sterility. Testicular Sertoli cells are the somatic cells that directly contact with spermatogenic cells in seminiferous tubules. They not only regulate immune response to maintain testicular immune homeostasis by secreting a variety of cytokines and immunosuppressive factors, but also provide the protective effects of spermatogenic cells by forming BTB. MC-LR induces inflammation and apoptosis of Sertoli cells, and destroys the integrity of the BTB, and then causes spermatogenesis dysfunction.
Male ; Humans ; Sertoli Cells ; Leucine/pharmacology* ; Arginine/pharmacology* ; Microcystins/metabolism* ; Immunity

Acetic acid is a common inhibitor present in lignocellulosic hydrolysate. Development of acetic acid tolerant strains may improve the production of biofuels and bio-based chemicals using lignocellulosic biomass as raw materials. Current studies on stress tolerance of yeast Saccharomyces cerevisiae have mainly focused on transcription control, but the role of transfer RNA (tRNA) was rarely investigated. We found that some tRNA genes showed elevated transcription levels in a stress tolerant yeast strain. In this study, we further investigated the effects of overexpressing an arginine transfer RNA gene tR(ACG)D and a leucine transfer RNA gene tL(CAA)K on cell growth and ethanol production of S. cerevisiae BY4741 under acetic acid stress. The tL(CAA)K overexpression strain showed a better growth and a 29.41% higher ethanol productivity than that of the control strain. However, overexpression of tR(ACG)D showed negative influence on cell growth and ethanol production. Further studies revealed that the transcriptional levels of HAA1, MSN2, and MSN4, which encode transcription regulators related to stress tolerance, were up-regulated in tL(CAA)K overexpressed strain. This study provides an alternative strategy to develop robust yeast strains for cellulosic biorefinery, and also provides a basis for investigating how yeast stress tolerance is regulated by tRNA genes.
Acetic Acid ; DNA-Binding Proteins/metabolism* ; Fermentation ; Leucine ; RNA, Transfer/genetics* ; Saccharomyces cerevisiae/metabolism* ; Saccharomyces cerevisiae Proteins/metabolism* ; Transcription Factors

3-methylcrotonyl-coenzyme A carboxylase (3MCC) deficiency is an autosomal recessive disorder in which leucine catabolism is hampered, leading to increased urinary excretion of 3-methylcrotonylglycine. In addition, 3-hydroxyisovalerylcarnitine levels increase in the blood, and the elevated levels form the basis of neonatal screening. 3MCC deficiency symptoms are variable, ranging from neonatal onset with severe neurological abnormality to a normal, asymptomatic phenotype. Although 3MCC deficiency was previously considered to be rare, it has been found to be one of the most common metabolic disorders in newborns after the neonatal screening test using tandem mass spectrometry was introduced. Additionally, asymptomatic 3MCC deficient mothers have been identified due to abnormal results of unaffected baby's neonatal screening test. Some of the 3MCC-deficient mothers show symptoms such as fatigue, myopathy, or metabolic crisis with febrile illnesses. In the current study, we identified an asymptomatic 3MCC deficient mother when she showed abnormal results during a neonatal screening test of a healthy infant.
Asymptomatic Diseases ; Fatigue ; Humans ; Infant ; Infant, Newborn ; Leucine ; Metabolism ; Mothers ; Muscular Diseases ; Neonatal Screening* ; Phenotype ; Tandem Mass Spectrometry

3-Methylcrotonylglycinuria is an autosomal recessive inborn error of leucine catabolism that results from the deficiency of 3-methylcrotonyl-CoA carboxylase(3-MCC). In 3-MCC deficiency 3-methylcrotonyl-CoA, may form glycine and carnitine conjugates. The primary metabolites are 3-hydroxyisovaleric acid(3-HIVA), 3-hydroxyisovaleryl carnitine(3-HIVC) and 3-methylcrotonylglycine(3-MCG). 3-hydroxyisovaleric acid(3-HIVA) and 3-methylcrotonylglycine(3-MCG) are increased in urine, and 3-hydroxyisovaleryl carnitine(3-HIVC) is found in blood and urine. 3-MCC is one of the four biotin- dependent carboxylases known in humans and is a heteromeric mitochondrial enzyme comprised of biotin-containing alpha-subunits and smaller beta-subunits. The gene for alpha-subunits(MCCC1) is located on chromosome 3q25-q27, beta-subunits(MCCC2) is located in 5q12-q13. Mutation in either of these genes may result in the deficiency of the enzyme activity. The introduction of tandem mass spectrometry in newborn screening has revealed an unexpectedly high incidence of this disorder and has also revealed that the range of clinical symptoms has become even wider ranging from neonatal onset with severe neurological involvement to asymptomatic newborns and adults. We report a case of a 43-day-old Korean asymptomatic girl with 3-Methylcrotonylglycinuria, detected by tandem mass spectrometry in newborn screening. This is resulted from the deficiency of 3-MCC by urine organic acid analysis. We found 2 mutations in the MCC2 gene of this patient. They are misssence mutation (D280Y) and splicing mutation(T357T). This patient on leucine restriction in conjunction with oral carnitine and glycine shows normal growth and development until now(10 months).
Adult ; Carnitine ; Female ; Glycine ; Growth and Development ; Humans ; Incidence ; Infant, Newborn* ; Leucine ; Mass Screening* ; Metabolism ; Tandem Mass Spectrometry*