Question

Rashid is a 50 year old patient who has been asked to fast for 24 hours before providing a blood test. a. Discuss what will happen to his glycogen stores after fasting and describe the pathway that will be used to maintain his energy.

Answer 1

In the human body, glycogen is a branched polymer of glucose stored mainly in the liver and the skeletal muscle that supplies glucose to the blood stream during fasting periods and to the muscle cells during muscle contraction.
Glycogen is both made and stored directly in the liver. When insulin goes up, the body stores food energy as glycogen. When insulin falls, as with fasting, the body breaks glycogen back down into glucose. Liver glycogen lasts approximately 24 hours without eating. Glycogen can only be used to store food energy from carbohydrates and proteins, not dietary fat, which is not processed in the liver, and does not break down into glucose.When glycogen stores are full, the body uses a second form of energy storage — body fat. Dietary fat and body fat are both composed of molecules called triglycerides. When we eat dietary fat, it is absorbed and sent directly into the bloodstream to be taken up by the adipocytes.
*The Fasted State
Our bodies only exist in one of two states — the fed state (insulin high) or the fasted state (insulin low). Our body is either storing food energy, or it is using it up. In the fasted state, we must rely on our stores of food energy to survive. The low insulin signals our body to use the stored food energy, because no food in coming in. First, we break glycogen down into glucose for energy. This lasts approximately 24 hours.
During the 4–24 hours of fasting phase, your body switches to the catabolic, or breakdown, state where stored nutrients are put to use. Once blood glucose and insulin levels drop, you’ll experience an uptick in glucagon—a catabolic hormone that stimulates the breakdown of glycogen (stored glucose) for energy. Since glucose is still your body’s main fuel source in this phase, your metabolism will attempt to break down enough glycogen to keep your blood glucose in the “normal” range (about 70–120 mg/dL).

Toward the end of this phase, you’ll likely start depleting your glycogen stores, which means you need access to another fuel source. Your body will begin the switch from glucose to ketones. Glucose is still your primary, preferred fuel source, but when your glucose reserves are nearing empty, you’ll start using fat stores and ketone bodies to make up the difference. Between 12 to 24 hours, blood glucose levels will be reduced by about 20%.

The exact time that your body starts shifting from using glucose to ketones for energy depends on how much glycogen you’ve got stored away and how much energy you’re burning throughout the day.
Glycogenolysis is the biochemical pathway in which glycogen breaks down into glucose-1-phosphate and glycogen. The reaction takes place in the hepatocytes and the myocytes. The process is under the regulation of two key enzymes: phosphorylase kinase and glycogen phosphorylase.

Blood glucose is a source of energy for the entire human body. During the fasting state, to maintain normal blood glucose levels, the liver plays a central role in producing glucose via glycogenolysis and gluconeogenesis.
Steps in glycogenolysis:-

1) In fasting state → glycogen phosphorylase is allosterically activated by glucose 6-phosphate and ATP (in liver, not in muscle, free glucose is also an activator) → glycogenolysis. In contrast, glycogen synthase is allosterically inhibited by glucose 6-phosphate and ATP → no glycogenolysis

2) During muscle contraction → membrane depolarization occurs by nerve impulses → increase calcium concentration in muscle cell → calcium binds with calmodulin → stimulates glycogen phosphorylase → glycogenolysis.

3) In muscle under extreme conditions of anoxia and ATP depletion → increase AMP level in muscle → stimulates glycogen phosphorylase → glycogenolysis.

*Steps in Gluconeogenesis:-

Gluconeogenesis is a pathway consisting of a series of eleven enzyme-catalyzed reactions. The pathway will begin in either the liver or kidney, in the mitochondria or cytoplasm of those cells, this being dependent on the substrate being used. Many of the reactions are the reverse of steps found in glycolysis.

Gluconeogenesis begins in the mitochondria with the formation of oxaloacetate by the carboxylation of pyruvate. This reaction also requires one molecule of ATP, and is catalyzed by pyruvate carboxylase. This enzyme is stimulated by high levels of acetyl-CoA (produced in β-oxidation in the liver) and inhibited by high levels of ADP and glucose.
Oxaloacetate is reduced to malate using NADH, a step required for its transportation out of the mitochondria.
Malate is oxidized to oxaloacetate using NAD+ in the cytosol, where the remaining steps of gluconeogenesis take place.
Oxaloacetate is decarboxylated and then phosphorylated to form phosphoenolpyruvate using the enzyme PEPCK. A molecule of GTP is hydrolyzed to GDP during this reaction.
The next steps in the reaction are the same as reversed glycolysis. However, fructose 1,6-bisphosphatase converts fructose 1,6-bisphosphate to fructose 6-phosphate, using one water molecule and releasing one phosphate (in glycolysis, phosphofructokinase 1 converts F6P and ATP to F1,6BP and ADP). This is also the rate-limiting step of gluconeogenesis.
Glucose-6-phosphate is formed from fructose 6-phosphate by phosphoglucoisomerase (the reverse of step 2 in glycolysis). Glucose-6-phosphate can be used in other metabolic pathways or dephosphorylated to free glucose. Whereas free glucose can easily diffuse in and out of the cell, the phosphorylated form (glucose-6-phosphate) is locked in the cell, a mechanism by which intracellular glucose levels are controlled by cells.
The final gluconeogenesis, the formation of glucose, occurs in the lumen of the endoplasmic reticulum, where glucose-6-phosphate is hydrolyzed by glucose-6-phosphatase to produce glucose and release an inorganic phosphate. Like two steps prior, this step is not a simple reversal of glycolysis, in which hexokinase catalyzes the conversion of glucose and ATP into G6P and ADP. Glucose is shuttled into the cytoplasm by glucose transporters located in the endoplasmic reticulum's membrane.