Structure of the human GlcNAc-1-phosphotransferase αβ subunits reveals regulatory mechanism for lysosomal enzyme glycan phosphorylation.

Vertebrates use the mannose 6-phosphate (M6P)-recognition system to deliver lysosomal hydrolases to lysosomes. Key to this pathway is N-acetylglucosamine (GlcNAc)-1-phosphotransferase (PTase) that selectively adds GlcNAc-phosphate (P) to mannose residues of hydrolases. Human PTase is an αβγ heterohexamer with a catalytic core and several peripheral domains that recognize and bind substrates.

Severe Hypertriglyceridemia-Induced Necrotizing Pancreatitis Associated With Ketogenic Diet in a Well-Controlled Patient With Type 2 Diabetes Mellitus.

The ketogenic diet (keto diet) has become an increasingly popular approach for both weight loss and as an alternative diet for type 2 diabetes mellitus (T2DM). Owing to the nature of the keto diet, patients are at risk of developing hypertriglyceridemia (HTG) due to the high amount of triglycerides consumed by individuals during the initiation of this diet. Acute pancreatitis can result from HTG.

Species-specific differences in the processing of acid α-glucosidase are due to the amino acid identity at position 201.

Acid α-glucosidase (GAA) is a lysosomal enzyme that hydrolyzes glycogen to glucose. Deficiency of GAA causes Pompe disease. Mammalian GAA is synthesized as a precursor of ~110,000 Da that is N-glycosylated and targeted to the lysosome via the M6P receptors.

A human model of selenium that integrates metabolism from selenite and selenomethionine.

Selenium (Se) metabolism is affected by its chemical form in foods and by its incorporation (specific vs. nonspecific) into multiple proteins. Modeling Se kinetics may clarify the impact of form on metabolism.

Structural basis for recognition of phosphodiester-containing lysosomal enzymes by the cation-independent mannose 6-phosphate receptor.

Mannose 6-phosphate (Man-6-P)-dependent trafficking is vital for normal development. The biogenesis of lysosomes, a major cellular site of protein, carbohydrate, and lipid catabolism, depends on the 300-kDa cation-independent Man-6-P receptor (CI-MPR) that transports newly synthesized acid hydrolases from the Golgi. The CI-MPR recognizes lysosomal enzymes bearing the Man-6-P modification, which arises by the addition of GlcNAc-1-phosphate to mannose residues and subsequent removal of GlcNAc by the uncovering enzyme (UCE).