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68 Cards in this Set
- Front
- Back
Which GLUT transporter is found in almost all tissues and provides basal glucose uptake? |
GLUT1 |
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Which GLUT transporter is found in liver, pancreatic cells, and the basolateral membrane of small intestines? |
GLUT2 |
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Which GLUT transporter removes excess glucose from the blood and plays a role in insulin secretion? |
GLUT2 |
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Which GLUT transporter is found in muscle and fat cells? |
GLUT4 |
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Which GLUT transporter is found in the mucosal membrane of the small intestine and spermatozoa? |
GLUT5 |
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Which GLUT transporter acts as a fructose transporter? |
GLUT5 |
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Which GLUT transporter is insulin sensitive? |
GLUT4 |
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What are the Km values of: GLUT1 GLUT2 GLUT4 GLUT5 |
GLUT1: 1-2 mM GLUT2: 15-20 mM GLUT4: 5 mM GLUT5: 10 mM (fructose) *normal blood glucose is 5 mM |
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What 2 channels are involved in the exocytosis of insulin from pancreatic beta cells? Which one opens and which one closes? |
ATP-sensitive K+ channel: closes -> Voltage-sensitive Ca++ channel: opens |
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Which drugs increase insulin secretion from pancreatic beta cells by mimicking ATP and binding K+ channels? |
Sulfonylureas and Meglitinides |
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Which drug decreases insulin secretion from pancreatic beta cells by opening ATP-dependent K+ channels? |
Diazoxide |
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What causes GLUT4 receptors to become active? Signaling through which receptor and which pathway?? |
- Insulin binds insulin receptors - PKB pathway - GLUT4 sequestered in intracellular vesicles gets brought to the membrane and becomes active |
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What does lack of insulin in T1 diabetics do to adipocytes? What is the response of the liver hepatocytes? |
Adipocytes hydrolyze TG fat stores Liver hepatocytes respond to increase FA content of blood by talking up FAs and metabolizing through B-ox or converting to ketone bodies -> diabetic ketoacidosis |
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What Hexokinase isoform is found in muscle tissues? Km? What inhibits it? |
Hexokinase I (II or III) Km = 0.05 mM, so basically always saturated Inhibited by: Glucose 6-P |
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Where is Glucokinase (Hexokinase IV) found? How is it different from Hexokinase I? |
Found in liver and pancreas Km = 100x Km of Hexokinase I Specific for glucose (no other hexoses) Not inhibited by glucose 6-P |
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How is glucokinase regulated? (Pathway) |
Low blood glucose -> buildup of Fructose 6-P in cell because of inhibition of PFK-1 -> enhanced function of GKRP (glucokinase reg protein) -> GKRP binds active cytosolic glucokinase and sequesters inside nucleus |
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Where is active glucokinase? Inactive glucokinase? |
Active: in cytosol Inactive: sequestered in nucleus |
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What is the regulation of PFK-1? Examples? |
Allosteric inhibition by: high ATP, citrate Allosteric activation by: high ADP/AMP, fructose 2,6-bisphosphate Other inhibition: H+ (lactate) Other activation: Fructose 6-phosphate (substrate) |
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Fructose 6-phosphate <-> Fructose 2,6-bisphosphate Forward enzyme? Reverse enzyme? |
Forward: PFK-2 Reverse: FBPase-2 |
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What is the most potent activator of PFK-1? What is the product of the PFK-1 reaction?
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Activator: Fructose 2,6-bisphosphate Product: Fructose 1,6-bisphosphate |
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What are the 2, related roles of F26BP? |
1: allosterically activates PFK-1 2: allosterically inhibits FBPase-1 |
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How does glucagon affect F26BP levels? (pathway) Overall result? |
Glucagon -> PKA -> phosphorylation of PFK-2/FBPase-2 enzyme, activating FBPase-2 domain -> breakdown of F26BP to F6P Overall: gluconeogenesis |
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How does insulin affect F26BP levels? (pathway) Overall result? |
Insulin -> phosphoprotein phosphatase -> dephosphory. of PFK-2/FBPase-2, activating PFK-2 domain -> production of F26BP Overall: glycolysis |
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What are positive regulators of Pyruvate kinase (PK)? |
1. substrates: ADP and phosphoenolpyruvate (PEP) 2. Fructose 1,6-bisphosphate |
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What are negative regulators of Pyruvate kinase (PK)? |
1. Well-fed state molecules (ATP, acetyl-CoA, LCFAs) 2. Alanine (from pyruvate) |
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What regulation is specific to liver pyruvate kinase? |
Inhibited: glucagon-PKA phosphorylation Activated: insulin-induced phosphatase activity |
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What is the pathway that bypasses step 7 of glycolysis in RBCs? |
1,3-BPG -> 2,3-BPG by bisphosphoglycerate mutase 2,3-BPG -> 3-phosphoglycerate by bisphosphoglycerate phosphatase |
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What is the most common deficiency causing hemolytic anemia? 2nd most common? |
1. Glucose 6-phosphate dehydrogenase (of PPP) 2. Pyruvate kinase |
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What could cause pyruvate kinase-based hemolytic anemia? |
1. Deficits in activating power of F16BP 2. Change in KM for PEP and ADP 3. Enzyme levels, stability, or activity 4. NOT DIRECTLY RELATED: Inability to compensate by increasing levels of 2,3 BPG (to release more O2 from fewer RBCs) |
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What chemicals inhibit glycolysis? |
1. 2-deoxyglucose (glucose analog) 2. Iodoacetamide (reacts with glyceraldehyde 3-phosphate dehydrogenase) 3. Arsenate (phosphate analog) 4. Fluoride (inhibits enolase rxn) |
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What is the first step of glycolysis? Substrates? Products? Enzyme? Energy input? |
Glucose -> Glucose 6-phosphate Hexokinase/Glucokinase Uses 1 ATP |
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Which has a higher Km, hexokinase or glucokinase? |
Gulcokinase |
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What are the 3 important results of converting glucose to glucose 6 phosphate? |
1. Invests energy (prep phase) 2. Creates a negative charge so glucose can't enter the cell 3. Glucose 6-P can be used for glycolysis, PPP, or glycogen synthesis |
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What is the third step of glycolysis? Substrates? Products? Enzyme? Energy input? |
Fructose 6-phoaphate -> fructose 1,6-bisphasphate PFK-1 Uses 1 ATP
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What step of glycolysis cleaves the molecule? Substrates? Products? Enzyme? |
Step 4 Fructose 1,6-bisphosphate -> DHAP + GAP Aldolase |
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What is the sixth step of glycolysis? Substrates? Products? Enzyme? Energy output? |
Glyceraldehyde 3-phosphate (GAP) -> 1,3-bisphosphoglycerate Glyceraldehyde 3-phosphate dehydrogenase Makes NADH x2 |
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What is the seventh step of glycolysis? Substrates? Products? Enzyme? Energy output? |
1,3-bisphosphoglycerate -> 3-phosphoglycerate Phosphoglycerate kinase Makes ATP x2 |
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What is the tenth step of glycolysis? Substrates? Products? Enzyme? Energy output? |
Phosphoenolpyruvate -> pyruvate Pyruvate kinase Makes ATP x2 |
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Glycolysis intermediates 1,3-Bisphosphoglycerate and 3-Phosphoglycerate can be converted to ______ which is involved in ____? |
2,3-Bisphosphoglycerate (2,3-BPG) Regulates oxygen release from hemoglobin |
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Glycolysis intermediate DHAP can be converted to _____ which is involved in _____? |
Glycerol 3-phosphate TG backbone/synth |
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Glycerol 6-phosphate can be directed towards? (3) |
1. Glycolysis 2. Glycogen synthesis 3. PPP |
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What additional step occurs when glycolysis occurs in anaerobic conditions? |
Pyruvate -> lactate By lactate dehydrogenase, costing 1 NADH/pyruvate |
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Glycogen is first broken into glucose monomers in the form _____, then converted to _______. |
Glucose 1-phosphate Glucose 6-phosphate |
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What enzyme does liver possess (not in muscle) that converts glucose 6-phosphate to glucose? In which pathways does this enzyme work? |
Glucose 6-phosphatase Glycogen breakdown and gluconeogenesis |
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What types of linkages are found in glycogen? |
a-1,4 (linear) a-1,6 (branching) |
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The reducing end of the glycogen molecule is the C_ end |
C4 |
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What is step 1 of glycogen synthesis? |
Glucose 6-phosphate -> glycose 1-phosphate By phosphoglucomutase |
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What is step 2 of glycogen synthesis? |
Glucose 1-phosphate -> UDP-glucose By UDP-glucose pyrophosphorylase (Activates glucose) |
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What enzyme transfers activated glucose to the nonreducing end of glycogen? |
Glycogen synthase |
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What enzyme catalyzes the generation of branches in glycogen? |
Glycosyl 4,6 transferase |
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What protein begins de novo synthesis of glycogen? |
Glycogenin |
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What is the enzyme of glycogenolysis that catalyzes the removal of single glucose a-1,4 linkages? What does it produce? |
Glycogen phosphorylase Glucose 1-phosphate |
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What are the 2 activities of the de-branching enzyme of glycogenolysis? What do they produce? |
Glucosyl 4,4 transglycosidase (eventually = glucose 1-phosphate) a-1,6 glucosidase (= glucose) |
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What hormone triggers glycogenolysis in liver? In muscle? |
Liver: glucagon Muscle: epinephrine |
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What cofactor does glycogen phosphorylase require? |
Pyridoxal phosphate (PLP) active form of B6 |
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Type 0 Glycogen Storage Disease: Enzyme affected? Primary organ? Symptoms? |
Glycogen synthase (makes 1,4 linkages) Liver Low blood glucose, high ketone bodies, early death |
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Type Ia (von Gierke's) Glycogen Storage Disease: Enzyme affected? Primary organ? Symptoms? |
Glucose 6-phosphatase (G6P -> glucose) Liver Enlarged liver, kidney failure |
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Type II (Pompe's) Glycogen Storage Disease: Enzyme affected? Primary organ? Symptoms? |
Lysosomal glucosidase (cuts 1,6 branches) Skeletal and cardiac muscle Infantile form: death by 2 Juvenile form: muscle defects Adult form: as in muscular dystrophy |
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Type IIIa (Cori's or Forbes's) Glycogen Storage Disease: Enzyme affected? Primary organ? Symptoms? |
Debranching enzyme Liver, skeletal, and cardiac muscle Enlarged liver in infants, myopathy |
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Type IV (Andersen's) Glycogen Storage Disease: Enzyme affected? Primary organ? Symptoms? |
Branching enzyme Liver, skeletal muscle Enlarged liver and spleen, myoglobin in urine |
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Type V (McArdle's) Glycogen Storage Disease: Enzyme affected? Primary organ? Symptoms? |
Muscle phosphorylase (removes 1,4 linkages) Skeletal muscle Exercise-induced cramps and pain, myoglobin in urine |
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What is the relationship between glycogen synthase, glycogen phosphorylase, and phosphorylation? |
Both are phosphorylated/de-phosphorylated at the same time Glycogen synthase is active when DEphosphy Glycogen phosphorylase is active when phosphor. |
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What enzyme phosphorylates glycogen phosphorylase? How is it activated? |
Phosphorylase kinase Activated by phosphorylation |
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How does phosphorylase kinase get phosphorylated/activated? |
GPCR -> cAMP -> PKA |
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What protein dephosphorylates glucose phosphorylase? What helps it to act in the liver? |
Phosphorylase phosphatase 1 (PP1) Glucose |
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What protein phosphorylates (deactivates) glycogen synthase? Dephosphorylates (activates)? |
Phosphorylates: Glycogen Synthase Kinase 3 (GSK3) Dephosphorylates: PP1 |
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What substances can allosterically activate Glycogen synthase? |
Activate: glucose or glucose 6P |
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What protein activates PP1 when phosphorylated, and then removes PP1 from the complex when further phosphorylated? |
Gm |