Lecture 12 Flashcards
(26 cards)
From what cells and organ are insulin, glucagon, and somatostatin produced and secreted from? These cells come together to form what circular structure?
Insulin, glucagon, and somatostatin are secreted from the pancreas.
Beta cells produce insulin.
Alpha cells produce glucagon.
Delta cells produce somatostatin.
The circular structure is known as islets of langerhans.
How do the pancreas and the gallbladder secrete “stuff” into the beginning of the small intestines? What is the beginning portion of the small intestines called?
The beginning portion of the small intestines is called the duodenum. The gallbladder secretes bile acid and bile salts into the duodenum through the common bile duct. The pancreas secretes “stuff” like bicarbonate and water into the duodenum through the pancreatic duct.
The pancreas is extremely well vascularized. What does this mean and why is it important?
When we say that the pancreas is well vascularized, it means that it has a rich blood supply with numerous blood vessels running through it. Being well vascularized in important for the pancreas because it is responsible for producing and releasing hormones such that it releases these hormones into the bloodstream. This rich blood supply allows these hormones to be quickly and efficiently transported throughout the blood to their target tissues and organs.
What type of hormone is insulin? How is it initially secreted and what occurs to allow for insulin maturation?
Insulin is a peptide hormone. Insulin is initially secreted as a pre-pro-hormone. After cleavage of the signal sequence and formation of disulfide linkages within the peptide, preproinsulin becomes converted to proinsulin. The disulfide linkages help hold the proinsulin in the proper shape. After the proinsulin is cleaved at specific sites, proinsulin finally becomes mature insulin and is able to bind to insulin receptors around the body.
What does the presence of the C peptide help indicate?
The presence of the C peptide helps in the indication/diagnosis of different types of diabetes. Whether or not the C peptide is there can help you see if you have insulin there or not.
Why does phosphorylation occur immediately when the glucose enters the cell? What is produced as a result of glucose getting trapped inside a cell and going through glycolysis?
Phosphorylation occurs immediately when the glucose enters the cell because the addition of a bulky/polar group onto the glucose will prevent the glucose from exiting the cell. As a result of being trapped in the cell, 2 ATP, 2 NADH + 2 H+, and 2 pyruvates are yielded.
What is the fate of pyruvate in the event that energy is needed under aerobic conditions?
Pyruvate is converted into Acetyl-CoA by the pyruvate dehydrogenase complex in the mitochondrial matrix. This acetyl-CoA will then get converted into reducing equivalents and energy through the TCA cycle in the mitochondrial matrix. These reducing equivalents will then go through the ETC such that energy is able to synthesized through ATP synthase.
What is the first step in amino acid breakdown? Amino acids can enter different pathways depending on the type of amino acid; there are two types of amino acids for this reason - what are they classified as, and what do they do?
The first step in amino acid breakdown is deamination. This amino group is processed through the urea cycle and excreted as urea.
The two different type of amino acids are glucogenic and ketogenic amino acids. Glucogenic amino acids are able to be broken down into pyruvate. If they are ketogenic, they are able to go into the TCA cycle in the mitochondrial matrix.
What do fatty acids get broken down into? What process does this and where does it occur?
Fatty acids are broken down into Acetyl-CoA through beta-oxidation which occurs in the mitochondrial matrix. This Acetyl-CoA is able to enter the TCA cycle to yield energy and reducing equivalents. Reducing equivalents are able to enter the ETC, donate their electrons, and thus ATP is able to be synthesized.
What happens in the event that you need energy and you have low blood sugar, such that all of your glycogen storages have been depleted?
Your body will break down stored fats for energy. Since we don’t have sugar, your body will begin to send any derivatives into sugar into gluconeogenesis. Since your body will convert sugar derivative molecules to carry out the TCA cycle back into glucose, this prevents Acetyl-CoA from being able to be converted into citrate.
As a result, Acetyl-CoA will be converted into acidic ketone bodies which will be sent to the brain and other vital organs, such that these ketone bodies are able to be converted back into glucose to obtain energy.
What organs are responsible for gluconeogenesis?
The liver (mostly), the kidneys (contributes a significant amount, about 20%), and also the intestines (to some extent for signaling)
In the fed state (where you eat and have energy), what pancreatic hormone dominates? What processes get activated and inhibited as a result of this hormone?
In the fasted state (low energy), what pancreatic hormone dominates? What processes get activated and inhibited as a result of this hormone?
Is each process either anabolic or catabolic?
Fed state: insulin is going to dominate. As a result of secretion of insulin by the pancreas, pathways involved in glucose uptake/oxidation, synthesis of glucose stores and fats, as well as protein synthesis are going to occur. Processes which require energy are going to be inhibited. Energy obtaining and excess energy storing processes will be activated. Anabolic processes are activated.
Fasted: Glucagon is going to dominate. Pathways involved in glycogen and fat breakdown, glucose release from the cell, as well as ketone body formation are going to occur. Those that enable storage of energy and obtaining of energy are going to be inhibited. Essentially, processes involved in mobilizing energy and increasing available fuel for cells/tissue will occur. Catabolic processes are activated.
Can your body store proteins/amino acids?
No, our body only stores carbohydrates and fat - protein is converted into either sugar derivatives or fat. Muscles are not storages for protein.
What signals your pancreas to release insulin? What happens as a result of this increase in blood insulin levels, and what inhibits the secretion of insulin?
When blood glucose levels begin to go up, this will signal to your pancreas (beta cells) to secrete insulin and will inhibit the secretion of glucagon from alpha cells. As a result of insulin levels increasing in the blood, tissues with receptors for insulin will increase glycogen synthesis, glycolysis, and fat synthesis. The liver will only really do glycolysis if glucose levels are high enough. The muscles will also increase glucose transport into the cells as a result of the formation of more GLUT4 transporters. When blood glucose levels start to decrease, this will trigger a negative feedback loop on the beta cells of the pancreas to inhibit the secretion of insulin into the blood.
How do livers end up becoming fatty? What happens in the event that a fatty liver is not treated? How is fatty liver treatable?
The fatty liver can result from alcoholism and overeating/obesity (alcoholic liver disease.) If it’s not treated a continues to obtain fat deposits, the liver tissue will start to harden (fibrosis.) Fibrosis can lead to cirrhosis of the liver –> liver cancer. Alcohol speeds up the process of obtaining fat deposits, cirrhosis, and liver cancer. It’s treatable by eating better and losing weight.
For individuals with diabetes, what occurs?
Their body assumes that they are starving because they can’t access the glucose in their blood, so their body begins to break down fats into Acetyl-CoA.
At the same time, gluconeogenesis is occurring in their livers, meaning that all available oxaloacetate in their livers are converted into glucose which is sent out of the cell to other cells/tissues.
When their body believes that it does not have sugar and sends all of the available sugar derivatives out into the bloodstream, it prevents the TCA cycle from being able to actually work. As a result Acetyl-CoA builds up. Because our body wants to be able to mobilize more fatty acids for energy, it needs to find a way to obtain more of the CoA, so it begins to convert it to ketone bodies. The ketone bodies will go out of the mitochondria, out of the cell, and to organs that need energy.
What are the three ketone bodies produced from Acetyl CoA? Which ketone body is measured as a result of fluctuation based on starvation? Which are used for energy/circulation, and which is used as an indicator for ketoacidosis?
Acetoacetate: formed first and used for energy
Beta-hydroxybutyrate: formed from deduction of carbonyl group of acetoacetate and is used for energy. it’s measured with a ketone meter since levels fluctuate a lot due to starvation.
Acetone: formed from decarboxylation of acetoacetate and is exhaled (indicator of ketoacidosis)
How does insulin secretion affect the location of GLUT4 transporters in a cell? What happens when insulin levels decrease?
When insulin is secreted, it will bind to receptors on the cell membrane. This will lead to endosomes fusing to the cell membrane and becoming part of the cell membrane to allow glucose to be able to come in to the cell. Insulin will also lead to an increase in transcription of these GLUT4 transporters.
When insulin levels drop, parts ot the membrane containing the GLUT4 transporters are going to pinch inwards (endocytosis) and produce an endosome which enters the cell. Only after glucose levels increase and insulin secretion increases as well, will the increase in transcription of GLUT4 transporters and transport of these to the cell membrane occur.
What enzymes are activated which enable the production of glycogen?
Hexokinase as well as glycogen synthase are activated as a result of insulin secretion.
When is the fasted state activated? What occurs during the fasted state, and what happens when the fasted state stops?
The fasted state is activated when we need energy and do not have any food. As a result of being in the fasted state, our body begins to break down storages of glycogen to raise blood sugar levels, with which this mobilized glucose will be able to go to organs in need. When plasma glucose levels drop, this will lead to the activation of alpha cells and inhibition of beta cells in the pancreas, which will allow blood glucagon levels to go up, and blood insulin levels to go down.
Glucagon will affect the liver to increase glycogen breakdown, gluconeogenesis, and produce ketone bodies. At the same time, muscles and adipose tissue are going to be recycling pyruvate and lactate (cori cycle) so that glucose levels in the blood can increase.
When blood glucose levels go up, glucose receptors will detect an increase in blood glucose.
When alpha cells are stimulated to secrete glucagon and why is it that blood insulin levels do not drop down to zero?
Glucagon stimulates glycogen breakdown and gluconeogenesis to increase blood glucose levels. Insulin still needs to be present such that the glucose that has been mobilized has to still be able to be taken up by cells that need energy.
Does the liver utilize ketone bodies when they are produced?
The muscles and brain utilize ketone bodies. The brain relies heavily on ketones when they are around.
How do glucagon and epinephrine affect fat degradation/synthesis pathways?
Glucagon and epinephrine are released under conditions of low blood sugar/energy.
They stimulate the increase in lipolysis. For fat synthesis, the committed step of fat synthesis will be inhibited. As a result, since Malonyl-CoA will not be synthesized, there will be nothing to inhibit Carnitine acyl transferase 1 (responsible for transporting fatty acids into the mitochondria from beta-oxidation,) so beta-oxidation will be active as well.
When your body gets into a severely fasted state, what else does your body begin to break down when energy is needed? Why is this important?
Your body begins to break down proteins. If blood sugar is low, muscles are able to be broken down such that they are able to act as a supply for these metabolites for gluconeogenesis.
This also helps supply metabolites necessary for the TCA cycle to be able to carry out, such that ketone bodies are able to be converted back into Acetyl-CoA in the muscles and the brain and be able to combine with oxaloacetate to yield reducing equivalents and energy for the electron transport chain. Glycerol from lipolysis are also able to serve as glucose precursors as well.
