Glycogen Metabolism and Lysosomal Storage Diseases

Study Notes

Lysosomal Storage Diseases

Lysosomal storage diseases are genetic disorders characterized by the accumulation of abnormal amounts of carbohydrates or lipids.
This accumulation occurs due to decreased lysosomal degradation resulting from decreased activity or amount of lysosomal acid hydrolases.

Glycogenesis and Glycogenolysis Regulation

Glycogenesis accelerates during periods of feeding, whereas glycogenolysis accelerates during periods of fasting in the liver.
In skeletal muscle, glycogenolysis occurs during active exercise, and glycogenesis begins during rest.
Regulation of synthesis and degradation is accomplished on two levels: hormonal regulation and allosteric regulation.

Covalent Activation of Glycogenolysis

The binding of hormones, such as glucagon or epinephrine, to plasma membrane G protein–coupled receptors signals the need for glycogen to be degraded.
This signals either elevate blood glucose levels or provide energy for exercising muscle.

Glycogen Storage Diseases (GSD)

GSD are a group of genetic diseases caused by defects in enzymes required for glycogen degradation or synthesis.
They result in either formation of glycogen with an abnormal structure or accumulation of excessive amounts of normal glycogen in specific tissues due to impaired degradation.
Only GSD II is lysosomal because glycogen metabolism occurs primarily in the cytosol.

Glycogen Structure and Synthesis

Glycogen is a highly branched polymer of α-D-glucose.
The primary glycosidic bond is an α(1→4) linkage.
After about 8–14 glucosyl residues, there is a branch containing an α(1→6) linkage.
UDP-glucose is synthesized from glucose 1-phosphate and UTP by UDP–glucose pyrophosphorylase.

Glycogenolysis Activation

Nerve impulses cause membrane depolarization, which promotes Ca2+ release from the sarcoplasmic reticulum into the sarcoplasm of myocytes.
Ca2+ binds the CaM subunit, and the complex activates muscle phosphorylase kinase b.
Epinephrine is released from the adrenal medulla and signals the need for blood glucose during physiologic stress.
Binding of epinephrine to hepatocyte α1-adrenergic GPCR activates a phospholipid-dependent cascade, resulting in movement of Ca2+ from the ER into the cytoplasm.

Description

Test your knowledge of glycogen synthesis and degradation, as well as lysosomal storage diseases, including Pompe disease. Learn about the importance of maintaining blood glucose levels and how genetic disorders affect carbohydrate and lipid metabolism.