Glycogen is a complex carbohydrate, the primary storage form of glucose in the human body. It is a multibranched polysaccharide, consisting of many linked glucose units. This structure allows for efficient storage and rapid glucose release. Glycogen is predominantly stored in the cells of the liver and skeletal muscles, though smaller amounts are found in other tissues like the kidneys and brain.
Why the Body Breaks Down Glycogen
The body breaks down glycogen to provide energy and maintain glucose balance. Liver glycogen regulates blood glucose levels throughout the body. When blood sugar falls, such as during periods of fasting or between meals, the liver converts its stored glycogen back into glucose and releases it into the bloodstream. This ensures tissues like the brain, which rely heavily on glucose, receive a continuous supply.
Muscle glycogen serves a different, more localized purpose, acting as an immediate energy source for muscle contraction. During physical activities, especially intense exercise, muscles utilize their glycogen reserves to fuel their work. This localized breakdown prevents the muscles from drawing too much glucose from the bloodstream, which would otherwise deprive other organs of necessary energy.
How Glycogen is Broken Down
The breakdown of glycogen, known as glycogenolysis, involves a series of enzymatic steps. This process primarily begins with glycogen phosphorylase, an enzyme that cleaves alpha-1,4 glycosidic bonds in glycogen’s linear chains, releasing glucose-1-phosphate. Glycogen phosphorylase continues to remove glucose units until four residues remain from an alpha-1,6 glycosidic branch point.
At these branch points, a debranching enzyme takes over. This enzyme has two distinct activities: glucan transferase and amylo-alpha-1,6-glucosidase. The glucan transferase activity moves three of the four remaining glucose units from the branch to another glycogen chain, forming a new alpha-1,4 linkage. This exposes the single glucose unit attached by an alpha-1,6 bond at the original branch point.
Following the transferase activity, the debranching enzyme’s amylo-alpha-1,6-glucosidase activity hydrolyzes the alpha-1,6 glycosidic bond, releasing the final glucose residue as free glucose. This is the only instance where free glucose is directly released, rather than glucose-1-phosphate. The released glucose-1-phosphate is then converted to glucose-6-phosphate by phosphoglucomutase.
In liver cells, glucose-6-phosphate can be converted to free glucose by glucose-6-phosphatase. This free glucose can then be released into the bloodstream to maintain blood glucose levels. Muscle cells, however, lack glucose-6-phosphatase. The glucose-6-phosphate produced from muscle glycogen breakdown is primarily used within the muscle cell for energy production through glycolysis.
Controlling Glycogen Breakdown
The body regulates glycogen degradation to meet energy demands and maintain a stable internal environment. Hormones play a role in this regulation, primarily glucagon and adrenaline (epinephrine).
When blood glucose levels are low, the pancreas releases glucagon, primarily targeting liver cells. Glucagon stimulates liver glycogen breakdown, releasing glucose into the bloodstream to raise blood sugar. Adrenaline, released during stress or physical exertion, also stimulates glycogen breakdown in liver and muscles. This provides a rapid glucose supply for muscle contraction and maintains blood glucose for other tissues. These hormonal signals activate a cascade of events involving protein kinase A (PKA) and phosphorylase kinase, which activate glycogen phosphorylase.
Beyond hormonal control, glycogen breakdown is also influenced by allosteric regulation, where molecules bind to enzymes at sites other than the active site to alter activity. For instance, in muscle cells, adenosine monophosphate (AMP) activates glycogen phosphorylase, promoting breakdown when cellular energy levels are low. Conversely, high levels of ATP and glucose-6-phosphate can inhibit glycogen phosphorylase, signaling ample energy and reducing the need for further breakdown.
Implications of Dysfunctional Glycogen Breakdown
When the glycogen degradation pathway malfunctions, it can lead to various health problems, collectively known as glycogen storage diseases (GSDs). These are genetic disorders resulting from deficiencies in specific enzymes involved in glycogen metabolism. This prevents the body from properly breaking down or utilizing stored glycogen, leading to its accumulation or an inability to access glucose when needed.
One common consequence of impaired liver glycogen breakdown, seen in types like Von Gierke disease (GSD I), is frequent low blood sugar (hypoglycemia) because the liver cannot release glucose. Symptoms include shaking, dizziness, and fatigue. In contrast, impaired muscle glycogen breakdown, as observed in some GSD types, can result in exercise intolerance, muscle weakness, and cramping, as muscles struggle to generate energy for activity.