更新于：2024-09-19

PYGM

更新于：2024-09-19

基本信息

别名

肌型糖原磷酸化酶、glycogen phosphorylase, muscle associated、Glycogen phosphorylase, muscle form

+ [6]

简介

Allosteric enzyme that catalyzes the rate-limiting step in glycogen catabolism, the phosphorolytic cleavage of glycogen to produce glucose-1-phosphate, and plays a central role in maintaining cellular and organismal glucose homeostasis.

关联

100 项与 PYGM 相关的临床结果

登录后查看更多信息

100 项与 PYGM 相关的转化医学

登录后查看更多信息

0 项与 PYGM 相关的专利（医药）

登录后查看更多信息

573

项与 PYGM 相关的文献（医药）

2024-09-25·Journal of Pediatric Endocrinology and Metabolism

New perspectives for the treatment and follow-up of glycogen storage disease type V: DL-3-hydroxybutyric acid with modified Atkins diet and quadriceps femoris shear wave elastography

Article

作者: Aktaş, Emine ; İnci, Aslı ; Özsaydı Aktaşoğlu, Ekin ; Emecen Şanlı, Merve ; Akdulum, İsmail ; Tümer, Leyla ; Ezgü, Fatih Süheyl ; Yaylı, Nezih ; Kılıç, Ayşe ; Okur, İlyas

AbstractObjectivesGlycogen storage disease type V is caused by the mutations in muscle glycogen phosphorylase gene. This is the first report which DL-3-hydroxybutyric acid was used in combination with modified Atkins diet for the treatment of a patient with glycogen storage disease type V and quadriceps femoris shear wave elastography was performed to evaluate the treatment efficacy.Case presentationA 13-year-old girl was referred with fatigue and muscle cramps with exercise and there were no pathological findings in physical examination. Creatine kinase levels with 442 U/L. No phosphorylase enzyme activity was detected in muscle biopsy, a homozygous c.1A>G (p.M1V) pathogenic mutation was found in PYGM gene. She was started on DL-3-hydroxybutyric acid and modified Atkins diet at age 16. Her walking and stair climbing capacity increased, the need for rest during exercise decreased. The stiffness of the quadriceps femoris exhibited a reduction.ConclusionsDL-3-hydroxybutyric acid and modified Atkins diet may provide an alternative fuel and shear wave elastography may be useful in demonstrating treatment efficacy. More clinical and pre-clinical studies are obviously needed to reach more definite conclusions.

2024-08-18·International Journal of Ophthalmology

Key genes and regulatory networks for diabetic retinopathy based on hypoxia-related genes: a bioinformatics analysis

Article

作者: Li, Dai ; Yu, Cai-Han ; Yang, Jie ; Gong, Lan-Lan ; Lyu, Xu-Dong

AIM: To prevent neovascularization in diabetic retinopathy (DR) patients and partially control disease progression. METHODS: Hypoxia-related differentially expressed genes (DEGs) were identified from the GSE60436 and GSE102485 datasets, followed by gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Potential candidate drugs were screened using the CMap database. Subsequently, a protein-protein interaction (PPI) network was constructed to identify hypoxia-related hub genes. A nomogram was generated using the rms R package, and the correlation of hub genes was analyzed using the Hmisc R package. The clinical significance of hub genes was validated by comparing their expression levels between disease and normal groups and constructing receiver operating characteristic curve (ROC) curves. Finally, a hypoxia-related miRNA-transcription factor (TF)-Hub gene network was constructed using the NetworkAnalyst online tool. RESULTS: Totally 48 hypoxia-related DEGs and screened 10 potential candidate drugs with interaction relationships to upregulated hypoxia-related genes were identified, such as ruxolitinib, meprylcaine, and deferiprone. In addition, 8 hub genes were also identified: glycogen phosphorylase muscle associated (PYGM), glyceraldehyde-3-phosphate dehydrogenase spermatogenic (GAPDHS), enolase 3 (ENO3), aldolase fructose-bisphosphate C (ALDOC), phosphoglucomutase 2 (PGM2), enolase 2 (ENO2), phosphoglycerate mutase 2 (PGAM2), and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). Based on hub gene predictions, the miRNA-TF-Hub gene network revealed complex interactions between 163 miRNAs, 77 TFs, and hub genes. The results of ROC showed that the except for GAPDHS, the area under curve (AUC) values of the other 7 hub genes were greater than 0.758, indicating their favorable diagnostic performance. CONCLUSION: PYGM, GAPDHS, ENO3, ALDOC, PGM2, ENO2, PGAM2, and PFKFB3 are hub genes in DR, and hypoxia-related hub genes exhibited favorable diagnostic performance.

2024-07-01·Journal of Biological Chemistry

Glycogen myophosphorylase loss causes increased dependence on glucose in iPSC-derived retinal pigment epithelium

Article

作者: Ladbury, John E ; Inglehearn, Chris F ; Basu, Basudha ; Johnson, Colin A ; China, Becky ; Karwatka, Magdalena ; Khan, Kamron ; McKibbin, Martin

Loss of glycogen myophosphorylase (PYGM) expression results in an inability to break down muscle glycogen, leading to McArdle disease-an autosomal recessive metabolic disorder characterized by exercise intolerance and muscle cramps. While previously considered relatively benign, this condition has recently been associated with pattern dystrophy in the retina, accompanied by variable sight impairment, secondary to retinal pigment epithelial (RPE) cell involvement. However, the pathomechanism of this condition remains unclear. In this study, we generated a PYGM-null induced pluripotent stem cell line and differentiated it into mature RPE to examine structural and functional defects, along with metabolite release into apical and basal media. Mutant RPE exhibited normal photoreceptor outer segment phagocytosis but displayed elevated glycogen levels, reduced transepithelial resistance, and increased cytokine secretion across the epithelial layer compared to isogenic WT controls. Additionally, decreased expression of the visual cycle component, RDH11, encoding 11-cis-retinol dehydrogenase, was observed in PYGM-null RPE. While glycolytic flux and oxidative phosphorylation levels in PYGM-null RPE were near normal, the basal oxygen consumption rate was increased. Oxygen consumption rate in response to physiological levels of lactate was significantly greater in WT than PYGM-null RPE. Inefficient lactate utilization by mutant RPE resulted in higher glucose dependence and increased glucose uptake from the apical medium in the presence of lactate, suggesting a reduced capacity to spare glucose for photoreceptor use. Metabolic tracing confirmed slower ¹³C-lactate utilization by PYGM-null RPE. These findings have key implications for retinal health since they likely underlie the vision impairment in individuals with McArdle disease.

项与 PYGM 相关的新闻（医药）

2024-01-10

·AIDD Pro

深度学习解密：蛋白质配体结合亲和力预测的新纪元！

今天给大家讲一篇2024年1月在Journal of Cheminformatics 上发表的运用深度学习方法预测蛋白配体结合亲和力的综述。本文回顾了基于结构的深度学习方法在药物发现中的应用，并讨论了分子表示方法、不同模型架构及模型可解释性等方面的重要性。通过一个分类体系对不同模型的打分和筛选能力进行了一系列评估，以此来揭示现有AI方法对基于结构的药物发现所带来的潜在益处。蛋白质-配体相互作用研究背景蛋白质-配体相互作用指的是蛋白质与小分子化合物之间的相互作用。化合物会与蛋白特定的结合位点发生相互作用，从而形成稳定的蛋白质-配体复合物。分子对接作为一种常见的计算化学方法，用于预测蛋白质与配体之间的结合方式。它能够有效地确定蛋白质-配体复合物的结合位姿，为药物设计提供了一定的帮助。然而，预测蛋白质与配体之间的结合亲和力仍然是一个备受挑战的问题。从亲和力指标中能够获得关于蛋白质与配体相互作用强度的关键信息，并且在药物的虚拟筛选和再利用中发挥着重要作用，为准确设计具有特定生物活性的化合物提供了重要的指导。模型介绍2.1 PLBAP模型架构（基于原子卷积模块）通过设计了多个原子卷积神经网络来预测蛋白配体绑定亲和力。如图1A所示，每个分子的输入为原子坐标及原子的类型，并用复合物和蛋白与配体之间的能量差来估计结合亲和值。其估值表示为。其中原子卷积神经网络（ACNN）模块包括原子类型卷积层和维度分别为32,32,16的三个全链接层。接着，通过将该表征通过聚合函数来预测能量差，从而将原子级别的信息提升到分子水平。图1原子卷积模块的特征提取方法2.2 PLBAP模型架构（基于图卷积模块）首先将配体及绑定位点中的原子构建了节点、化学键的特征矩阵以及邻接矩阵。在邻接矩阵中，非共价相互作用的值比共价键的值要低（图2A）。输入的分子经过多个图卷积模块将节点的邻居节点的特征进行聚合以更新节点的表示。这个过程可以通过多轮的消息传递来实现，每一轮都通过聚合邻居节点的信息来更新节点的特征。这有助于模型在不同层次上捕捉分子结构的局部和全局特征，提高对分子特征提取的完整性。具体而言，每个图卷积模块包含三个维度为128、128和32的卷积层和三个全连接层并聚合，最后将它们输入到一个全连接输出结合亲和力（图2B）。图2 图卷积模块的特征提取方法实验结果3.1模型性能评估作者将PDBbind Refined 集合作为训练集，Core 集合作为验证集，CSAR-HiQ数据集作为外部测试集，并评估了四种方法预测亲和力的性能，评价指标为预测结合亲和力与真实结合亲和力的Pearson相关系数和均方根误差(RMSE)。较高的PC和较低的RMSE表示较好的预测性能。如图3所示，基于网格的CNN架构易于过拟合。此外，在外部测试集中，图卷积模块的预测性能相较于其他方法更有优势。图3 模型预测性能评估3.2 筛选性能评估作者选择了DUD-E数据集上两个靶标用于评估模型的筛选性能，肌肉糖原磷酸化酶（PYGM）和表皮生长因子受体（EGFR）。PYGM数据集有114个活性化合物和4045个阴性样本，并用AutoDOCK Vina为它们生成蛋白配体复合物。筛选效果如图4所示，当阴阳比增大时，富集率急剧下降。其中基于网格的CNN模块在筛选性能上具有一定的优势（top 1%时EF超过40），有望帮助药化专家加速潜在药物分子的筛选。图4筛选性能评估结论基于（PLBAP）模型来预测蛋白质与配体之间的结合亲和力可有效加速药物筛选中的效率。其中原子卷积神经网络模块适合大批量数据的计算。然而在打分或筛选任务上表现效果不佳。网格卷积模块利用了分子结构和体素化信息来提取表征，不过由于不满足旋转不变性使得在筛选任务中缺乏优势。分子图卷积模块可以更灵活地捕获分子拓扑结构，使其在筛选任务中具有竞争力。在未来，通过完善分子图的表示方法，并增强模型的可解释性，有助于在药物筛选方面提供更加智能、高效的解决方法。参考文献Cummings, M. D. & Sekharan, S. Structure-based macrocycle design in small-molecule drug discovery and simple metrics to identify opportunities for macrocyclization of small-molecule ligands. J. Med. Chem. 62, 6843–6853 (2019)版权信息本文系AIDD Pro接受的外部投稿，文中所述观点仅代表作者本人观点，不代表AIDD Pro平台，如您发现发布内容有任何版权侵扰或者其他信息错误解读，请及时联系AIDD Pro (请添加微信号sixiali_fox59)进行删改处理。本文为原创内容，未经授权禁止转载，授权后转载亦需注明出处。有问题可发邮件至sixiali@stonewise.cn关注我，更多资讯早知道↓↓↓