for mutation in glycogen metabolism. what happen if
a) loss of the gene that encodes alpha 1,4 glucosidase
b)loss of the gene that encodes Glucose-6-phosphatase in liver.
To understand the consequences of mutations in glycogen metabolism, let's explore the effects of losing the gene that encodes alpha 1,4 glucosidase (also known as glycogen debranching enzyme) and the gene that encodes Glucose-6-phosphatase in the liver.
a) Loss of the gene that encodes alpha 1,4 glucosidase:
Alpha 1,4 glucosidase is an enzyme involved in glycogen metabolism. It functions by breaking the alpha 1,4-glycosidic linkages in glycogen, allowing for the release of glucose molecules. If the gene responsible for encoding this enzyme is lost due to a mutation, the activity of alpha 1,4 glucosidase will be impaired or absent. This will result in a condition known as glycogen storage disease type III (also called Cori disease or Forbes disease).
Without alpha 1,4 glucosidase, glycogen breakdown is inefficient. Consequently, glycogen molecules cannot be fully degraded, leading to the accumulation of abnormal glycogen structures called limit dextrins. These limit dextrins cannot be further processed and broken down into glucose, preventing the release of glucose from glycogen. As a result, individuals with this condition may experience symptoms such as muscle weakness, hypoglycemia (low blood sugar), and an enlarged liver (hepatomegaly).
b) Loss of the gene that encodes Glucose-6-phosphatase in the liver:
Glucose-6-phosphatase is an enzyme found predominantly in the liver. It plays a vital role in glycogen metabolism by catalyzing the final step in glycogen breakdown. This enzyme converts glucose-6-phosphate (G6P), a product of glycogenolysis (the breakdown of glycogen), into free glucose that can be released into the bloodstream. If the gene encoding Glucose-6-phosphatase is lost due to a mutation, it will result in a condition known as glycogen storage disease type I (GSD I), also called von Gierke's disease.
When Glucose-6-phosphatase is absent, glucose-6-phosphate cannot be converted to glucose for release into the bloodstream. Consequently, glycogen breakdown is hindered, leading to an accumulation of glycogen within liver cells. This excessive glycogen storage in hepatocytes causes an enlarged liver, resulting in hepatomegaly. Additionally, individuals with GSD I experience severe hypoglycemia, which can lead to symptoms like excessive hunger, poor growth, and development, as well as an increased risk of liver and kidney complications.
In both cases, mutations disrupting glycogen metabolism enzymes impair the breakdown of glycogen, leading to abnormal glycogen accumulation in tissues and resultant symptoms affecting various organs and systems in the body.