Diabetes Dilemmas
These are 2-3 barriers to treatment that our patients Jason had to encounter.
What are cost of insulin (SES), illiteracy (his understanding of carbs), irregular schedule, and stress from moving?
Other semi-answers: low locus of control (relied on advice from parents/sister); Jason falls into the second-highest prevalence racial demographic
The intermediate of TCA that inhibits PFK-1
Citrate
Three characteristic lab findings of DKA
Hyperglycemia, acidosis, ketonemia
Two other common ketone bodies other than acetone:
acetoacetate
beta-hydroxybutyrate
After several weeks of fasting, the brain gets x amount of energy from ketones and y amount of energy from glucose.
After several weeks of fasting, the brain gets 2/3 amount of energy from ketones and 1/3 amount of energy from glucose.
The difference between Type I and Type II Diabetes.
Type I = Immune system attacks pancreas beta cells in the pancreas' islets of Langerhans
Type II = Decreased sensitivity to insulin and/or decreased insulin production
The four possible fates of pyruvate
Alanine, oxaloacetate, acetyl-CoA, and Lactate
Explain the cause of Jason's hyperglycemia.
Insulin medication noncompliance + fasting.
Pyruvate can't travel in the bloodstream. Name two cycles it will utilize in order to travel in the bloodstream?
Cahill cycle (alanine, glucose), Cori cycle (lactate, glucose)
Compare Km, Vmax, and location of hexokinase versus. glucokinase
Km and Vmax of hexokinase is lower than glucokinase. Hexokinase is distributed throughout most tissue, while glucokinase is present in the liver and pancreas
1st and 2nd most common presentations for type 1 diabetes
1) Hyperglycemia without acidosis
2) Diabetic Ketoacidosis
The pathways that glucose-6-phosphate can be shunted to.
HMP Shunt, glycogenesis, glycogenolysis
We know that Jason experienced ketoacidosis. What 3 ketones are involved in DKA, and what are their "fates"?
Acetone --> fruit breath
Acetoacetate (acetoacetic acid) + B-hydroxybutyrate (B-hydroxybutyric acid) --> release H+, decreasing pH
Name 4 organs involved in metabolism and how they are involved in metabolism.
Adipose tissue: synthesizes, stores TGLs
Pancreas: secretes insulin, glucagon
Liver: processes fats, proteins, and carbs; stores glycogen
Kidneys: Involved in gluconeogenesis during fasting.
Intestines: Absorb nutrients from digested food and release hormones that regulate appetite and digestion.
Trace a pathway from glycogen to fatty acids (e.g. this substrate gets broken down into this by this pathway and then it needs to go down a different pathway to be created into...)
Name the pathway and which organelle it takes place in (e.g. this substrate gets broken down into this final product in the mitochondria). Don't mention any shuttles. Don't name any specific intemediates.
After 5 days of not using insulin, where was blood glucose being derived from?
Gluconeogenesis
The question asked for blood glucose.
The inhibitors and activators of each rate-limiting step of glycolysis
Step 1: inhibitors: HK=G-6-P; activators: GK=Insulin
Step 2: inhibitors: ATP, citrate; activators: AMP, F-2,6-BP, insulin (indirectly)
Step 3: inhibitors: ATP, citrate; activators: Fructose-1,6-BP, insulin (indirectly), AMP
According to Le Chatelier's Principle, what what lab value is directly affected by increasing [H+], and is it high or low? Why?
The H+ given off from the ketoacids reacts with bicarbonate because the reaction would shift to decrease the amount of [H+] in the system, thereby decreasing bicarbonate as a result. HCO3- lab value is low.
Glucose 6-phosphatase:
Name the function of this enzyme. Name in which organ(s) this enzyme lives. How does insulin affect it?
Converts glucose 6-phosphate to glucose
Found in the lumen of ER in liver cells and kidney
Insulin inhibits the enzyme.
Why is it advantageous that RBCs don't have mitochondria? (2 reasons why)
Maximize volume in RBC
Stopping the RBC from using the oxygen it's supposed to be carrying
In the context of diabetes type I, name the relationship/pathway between insulin, GLUT transporters, glucose, and "glucagon:insulin ratio".
Insulin in the blood will stimulate the insulin receptor, "which will start a pathway to allow GLUT4 transporters to fuse with the plasma membrane. Once the GLUT4 transporters are on the membrane, they can allow glucose in the blood to enter the cell. Since blood levels of insulin have dropped in Type I with our patient, the insulin receptor isn't activated, and GLUT4 transporters cannot be on the surface of the cell to take in glucose. Thus, in order to get energy, cells are forced to turn fatty acids into ketone bodies." Also happening at the same time, "patients have an increased glucagon:insulin ratio, leading to constant activation of the glucagon-cAMP-PKA pathway. This pathway promotes phosphorylation of F26BP/PFK2 complex which inactivates PFK1 and activates FBPase1, preventing glycolysis from occurring. Since gluconeogenesis is occurring without regulation, blood glucose is too high."
Draw the 3 major steps of both glycolysis and 4 major steps of gluconeogenesis (include substrates, products, and enzymes)
Glycolysis: glucose->glucose-6-phosphate via hexokinase or glucokinase; fructose-6-phosphate-> fructose-1,6,bisphosphate via PFK1; PEP->pyruvate via pyruvate kinase
Gluconeogenesis: Pyruvate->OAA->Phosphoenolpyruvate via pyruvate carboxylase and PEP carboxykinase; Fructose-1,6-bisphosphate -> Fructose-6-phosphate via F-1,6-BP; Glucose-6-Phosphate -> Glucose via glucose-6-phosphatase
Diagram the blood buffer system and how it relates to DKA. Hint: Remember the slides I imported on Le Chatelier (sorry this is biased ❤️)
Please see document on Word. Jeopardy wouldn't let me import a picture unfortunately.
Synthesize a metabolic acidosis pathway on the whiteboard using the following key terms: protein degradation, urea, gluconeogenesis, fatty acids, ketone bodies, brain.
Once glycogen stores are depleted, gluconeogenesis becomes the primary source of glucose for the brain. Muscle tissue is broken down into amino acids through amino acid catabolism. The urea cycle processes the byproducts of ammonia (NH3), while the citric acid cycle incorporates glucogenic amino acids for energy production. Fatty acids undergo beta oxidation to convert into acetyl-CoA, which is then used to produce ketone bodies through ketogenesis. The brain can utilize these ketone bodies or glucose as sources of energy during this fasting state.
Draw glycogenolysis starting with branched glycogen and name the key enzymes involved.
branched glycogen --> unbranched glycogen (via debranching enzyme / a-1,6-glucosidase) --> glucose-1-phosphate (via glycogen phosphorylase) --> glucose-6-phosphate (via glucomutase) --> glucose (via glucose-6-phosphate in the LIVER)
Bonus: unbranched glycogen --> glucose via lysosomal a-1,4-glucosidase in the LYSOSOME