Biochemistry Video 18
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- How is glucose traped inside the cells after going through the transporter?
- They are phosphorylated. This is done by hexokinase (found in any tissue and used most often) and glucokinase (found only in the liver)
- What is the difference in inducing and activating an enzyme?
- inducing an enzyme means that you are increasing the genetic expression of an enzyme whereas activating an enzyme activates an already existing enzyme
- hoe does insulin affect glucokinase?
- insulin inducers the expression of glucokinase
- What is an important fact about glucokinase which helps it achieve the same thing as the GLUT1 and GLU3 transporters?
- it has a low affinity for glucose, thus preventing the liver from keeping too much glucose coming from the gut.
- What is hexokinases affinity for glucose?
- hexokinase has a very high affinity for glucose.
- What does hexokinase and glucokinase convert glucose to?
- glucose 6-P
- What is the effect of glucose 6-P on hexokinase and glucokinase?
- it inhibits hexokinase
- What do we use to convert glucose to glucose 6-P?
- we use either hexokinase or glucokinase in combination with ATP
- What is fructose 6P converted to and what is required for this?
- Fructose-6P is converted to Fructose- 1, 6-BisPhosphate by PFK-1 and ATP
- What is the rate limiting step for glycolysis?
- PFK-1 conversion of fructose-6P to Fructose-1,6-bis P
- What is the next step in glycolysis from fructose-1, 6-BisPhosphate?
- it is converted by ALDOLASE to Glyceraldehyde 3P and DHAP (dihydroxyacetone phosphate). These are reversible reactions and glyceraldehyde 3P can be converted to DHAP via isomerase
- What happens to glyceraldehyde 3P?
- the is converted to 1,3-Bisphosphoglycerate via GLYCERALDEHYDE 3P DEHYDROGENASE. Thus losing a phosphate and producing NADH from NAD
- What happens to 1,3 bisphosphoglycerate (1,3 BPG)?
- It is converet to 3-phosphoglycerate by phosphoglycerate kinase. Thus because a Phosphate is lost in this process an ATP is produced
- What happens to 3-phosphoglycerate?
- it is made into 2-phosphoglycerate by the mutase enzyme
- What happens to 2 phosphoglycerate?
- it is converted to phosphoenolpyruvate by enolase (PEP)
- What happens to phosphoenolpyrubate?
- it is converted to pyruvate via pyruvate kinase?
- what is the significance of the pyruvate kinase enzyme?
- it is one of two substate level productions of ATP, the other being the conversion of 1,3 bisphosphoglycerate to 3phosphoglycerate via phosphoglycerate kinase
- What are the three reactions of glycolysis that create ATP
- 1. glyceraldehyde 3P dehydrogenase produces NADH which has the potential to produce ATP⬦⬦⬦..2. phosphoglycerate dehydrogenase produces ATP⬦⬦⬦⬦.3. Pyruvate kinase produces ATP
- What is the rate limiting step of glycolysis?
- it is the conversion of Fructose-6P to Fructose-1, 6-bisphosphate by PFK-1
- With PFK-1 being the rate limiting step of glycolysis, what activates the PFK-1 and thus glycolysis?
- It is indirectly activated by insulin through PFK-2
- how is PFK-1 activated via insulin through PFK-2?
- PFK-2 is actually directly activated by insulin⬦.PFK-2 converts Fructose-6P to Fructose 2, 6-bisP⬦.it is the Fructose 2,6-bisP that actually activates the PFK-1
- In what tissues is glycolysis not effected by the insulin level?
- red cells and brain cells
- how does glucagon have it’s effect on glycolysis?
- glucagon inhibits PFK-2, and thus inhibits the production of fructose 2,6-bisP and thus inhibits the stimulation of PFK-1
- How does insulin have it’s effect on PFK-2? glucagon?
- it dephosphorylates PFK-2, thus the dephosphorylated form of PFK-2 is the active form of PFK-2⬦⬦⬦⬦.glucagon willl phosphorylate PFK-2, and thus the phosphorylated form is the inactive form
- What is the only enzyme deficiency in glycolysis that clinically relevant?
- pyruvate kinase
- What is the result of a lack of an enzyme used in glycolysis in red cells?
- hemolysis (lysing of the red cell)⬦thus hemolytic anemia
- When are Heinz bodies seen in hemolytic anemia?
- G6PD deficiency
- Thus, if there is a hemolytic anemia, but no Heinz bodies, what should you expect?
- glycolysis enzyme deficiency
- What is an apparent problem with ontinually running glycolysis in a red blood cell?
- use up all NAD in the Glyceraldehyde 2P dehydrogenase reaction
- How is the NAD is a red blood cell replenished?
- Lactate Dehydrogenase, in the conversion of pyruvate to Lactate will convert NADH to NAD wand thus replenish the NAD in the red blood cell
- When is the use of lactate dehydrogenase essential to replenish the NAD?
- anytime that the electron transport chain is not available⬦⬦⬦this could be due to lack of mitochondria (red cell) or lack of oxygen
- What is anaerobic glycolysis?
- when glucose goes to Lactate
- What is aerobic glycolysis?
- when glucose goes to pyruvate
- What is the mechanism of the pathogenisis associated with hypoxia to the heart?
- because the heart will not be able to produce adequate ATP solely form from glycolysis, the Na/K pump will not be pumping at an adequate amount and thus there will be sodium influx into the cell. This will tend to depolarize the cell, and thus cause arrhythmias. The increasae sodium will also increase the intracellular osmolarity and thus the cell will swell. The cell swelling will eventually result in irreversible damage to the membrane and cell leakage of intracellular contents
- In myocardial infarction, what enzymes do you look for and when do they peak?
- LDH – does not show up as quick but stays in blood longer………….. CPK-MB – peaks relitavely rapidly (measurable in 6-8 hours)………….. troponins
- What does aldolase convert Fructose 1,6-bisphosphate to?
- glyceraldehyde 3P and Dihydroxyacetone-P (DHAP)
- What is dihydroxyacetone-P converted to and what enzyme does this?
- Dihydroxyacetone-P is converted to Glycerol-3P via glycerol-3P Dehydrogenase
- What is the significance of glycerol-3P?
- it is essential in the production of fat⬦⬦⬦and is a link to the electron shuttle
- in aerobic glycolysis, what happens to pyruvate?
- it goes to the mitochondria and is converted to Acetyl-CoA via pyruvate dehydrogenase.
- What happens to Acetyl CoA in the mitochondria?
- if ATP is needed, it enter the Krebs cycle, and if ATP is not needed, it will produce fatty acids
- Where is 2,3-BPG made?
- it is only made in the liver by the conversion of the glycolysis intermediate 1,3-bisphosphoglycerate to 2,3-bisphosphoglycerate
- What does HbA stand for and what is it composed of?
- HbA is adult hemoglobin and it is composed of 4 subunits: 2 alpha and 3 beta subunits
- How does 2,3 BPG produce its effects?
- it bonds to the Beta subunits of Hemoglobin A
- What is the effect of 2,3 BPG?
- it lowers the affinity of oxygen to hemoglobinby binding to the Beta subunits of the hemoglobin
- Is 2,3 BPG essential for life?
- yes 2,3 BPG is essential to life because without it attached hemoglobin would hold onto oxygen too tightly and not distribute it to the tissues
- What are the shuttles used to transport NADH from the cytoplasm into the mitochondria?
- malate shuttle and the Glycerol-3P Shuttle
- How does NADH use the malate shuttle?
- NADH will borrow some oxaloacetate. By giving oxaloacetate the good part of the NADH, the Hydrogen, the oxaloactate becomes malate which can freely enter the mitochondria via the malate shuttle
- What does NADH feed it’s electron to and how many ATP does it produce?
- it feeds it’s electrons to COMPLEX 1 and produces 3 ATPs
- How does NADH use the glycerol 3P shuttle to enter the mitochondria?
- NADH will not actually enter the mitochondria using the glycerol-3P shuttle. NADH will give a proton to DHAP to make it glycerol 3P⬦glycerol-3P is then able to give the proton to FAD to form FADH2, which is is the inner mitochondrial membrane. The FADH2 wil then take the Hydrogen and electrons to the electron transport chain
- What part of the electron transport chain will electrons entering the mitochondria through the glycerol-3P shuttle go to?....and how many ATP will they produce?
- electrons coming from the glycerol-3P shuttle will go to CoQ in the electron transport chain and will produce 2 ATPs.