9/28/12 Directed study
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| What does glycolysis do? | Cleaves and oxidizes glucose
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| What are the products of glycolysis? | pyruvate, ATP (small amount), and NADH
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| Where does glycolysis occur? | Cytosol of cell
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| Is glycolysis easily reversed? | No, it has an overall negative delta G
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| What is the reverse process of glycolysis? | Gluconeogenesis
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| Does gluconeogenesis require any input? | Yes, energy and special mechanisms to get around irreversible steps.
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| Is glycolysis an aerobic process? | No (required for production of energy from glucose either aerobically or anaerobically)
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| What process must be active for the synthesis of glycogen or fatty acids to take place? | glycolysis
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| What are required starting materials for glycolysis? | NAD+ and ADP
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| WHat facilitative transporters allow glucose to get into the cell? | GLUTs
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| Which cells have high affinity (low km) transporters highly expressed on the cell surface? | Red blood cells, brain tissue
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| What organ has low affinity glucose transporters? | liver
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| Which tissues have insulin-sensitive transporters? | Muscle and adipose
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| What are the characteristics of insulin transporters? | High affinity for glucose, but a small number present. They are transported in vesicles
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| How does "trapping" of glucose inside the cell occur? | Phosphorylation. Glucose 6 phosphate can't cross the membrane.
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| What enzyme catalyzes the reaction of Glucose to Glucose 6 phosphate? | Hexokinase
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| What are the characteristics of the brain isoform of hexokinase? | Low km for glucose, not regulated by insulin
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| What are the characteristics of the muscle isoform of hexokinase? | higher km for glucose, upregulated by insulin
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| What are the characteristics of the liver isoform of hexokinase? | Even higher kim, also upregulated by insulin
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| What is the liver isoform of hexokinase inhibited by? | Glucagon
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| What is the liver isoform of hexokinase called? | glucokinase
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| What are the three things glucose 6 phosphate can be used for? | glycolysis process, pentose phosphate pathway, glycogen
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| What is the glucose 6 phosphate isomerized to? | fructose 6 phosphate
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| What is fructose 6 phosphate phosphorylated to? | fructose 1,6 biphosphate
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| What is the enzyme that catalyzes this step? | phosphofructokinase-1
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| What is the rate limiting enzyme in glycolysis? | phosphofructokinase-1
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| What is the muscle isoform of PFK-1 activated by and inhibited by? | Activated by AMP, inhibited by ATP
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| What does fructose 1,6 biphosphate then split into? | dihydroxyacetone phosphate, glyceraldehyde 3 phosphate
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| Can DHAP and G3P be interconverted to one another? | Yes
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| What is the product of the final reversible reactions? | Phosphoenolpyruvate
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| What enzyme convertes phosphoenolpyruvate to pyruvate? | Pyruvate kinase
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| What tissue upregulates pyruvate kinase with insulin, and inhibits it with glucagon? | liver
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| What tissue does not regulate pyruvate kinase activity? | muscle
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| How does formation of NADH occur in glycolysis? | Reduction of NAD+
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| What must occur before glycolysis to continue? | Oxidation of the NADH back to NAD+
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| What are the two main ways of regenerating the NAD+? | Donation of an NADH electron to the electron transport change (oxidative phosphorylation), lactase dehydrogenase reaction (important for anaerobic tissues)
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| What must pyruvate be converted to to be used for aerobic ATP production? | acetyl CoA
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| What enzyme catalyzes the change from pyruvate to acetyl CoA? | pyruvate dehydrogenase
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| Where does this process occur and is it reversible? | mitochondria, no
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| What does pyruvate dehydrogenase control? | flow of pyruvate into the TCA cycle
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| What does the mechanism of regulation by pyruvate dehydrogenase complex involve? | phosphorylation/dephosphorylation of PDH
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| What is the PDH activated and inhibited by? | Activated by substrates, ADP, and calcium. Inhibited by products and ATP
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| What does exercising muscle cause? | Elevated calcium and ADP levels
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| What does elevated calcium and ADP levels encourage? | The production of acetyl CoA from pyruvate only if the tissue is well oxygenated.
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| What are the substrates and products of the TCA cycle? | Carbons from acetyl CoA are oxidized to produce CO2, NADH, FADH2
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| What are the NADH and FADH2 reoxidized through oxidative phosphorylation to produce? | ATP
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| What is the TCA cycle required to generate ATP from? | ketones, fatty acids, alcohol, amino acids
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| What occurs in the first step of the TCA cycle? | Oxaloacetate condenses with acetyl CoA to form citrate
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| Is the oxaloacetate recycled? | Yes
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| What is the key rate limiting enzyme of the TCA cycle? | isocitrate deydrogenase
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| What is isocitrate dehydrogenase stimulated and inhibited by? | Stimulated by ADP and calcium, inhibited by NADH
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| What is the citrate intermediate used for? | Fatty acid synthesis
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| What is the succinyl CoA intermediate required for? | Synthesis of heme
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| What enzyme catalyzes the synthesis of oaloacetate from pyruvate? | pyruvate carboxylase
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| Can acetyl CoA cross the mitochondrial membrane? | No
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| What is acetyl CoA converted to so it can cross the mitochondrial membrane to the cytosol? | Citrate
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| What is the citrate in the cytosol converted into so it can be used to make fatty acids? | acetyl CoA
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| What is PFK-1 in the liver controlled by? | Inhibited by ATP and citrate, activated by AMP
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| Which enzyme in the liver can override the signal to shut down PFK-1 in the liver? | PFK-2
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| What does PFK-2 do? | converts some of the fructose 6-phosphate formed in glycolysis to fructose 2,6 biphosphate
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| What is PFK-2 stimulated and inhibited by? | Stimulated by insulin, inhibited by glucagon
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| What are all three of the irreversible enzymes of glycolysis stimulated by? | insulin
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| What are they inhibited by? | Glucagon
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| What is the enzyme upregulated by insulin in muscle? | Hexokinase
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| Do muscle cells have glucagon receptors? | NO
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| What about the structure of glucagon makes it easily released? | Branched structure
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| What is added to the glucose 1-phosphate to activate the glucose? | UDP
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| What enzymes are used to build glycogen? | glycogen synthase, branching enzyme
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| What enzyme is the regulated step? | Glycogen synthase
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| What enzymes are used to breakdown glycogen? | Glycogen phosphorylase, debranching enzyme
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| Which enzyme is the regulated step? | Glycogen phosphorylase
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| What is glucose 6 phosphatase? | In the liver, allows glucose 6 phosphate to be converted back to glucose
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| Where does insulin signal through? | tyrosine kinase receptor
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| What does glucagon and epi signal through? | GPCRs
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| What is glycogen synthase stimulated and inhibited by? | Stimulated by insulin, inhibited by glucagon and epi
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| What is glycogen phosphorylase stimulated and inhibited by? | Stimulated by glucagon and epi, inhibited by insulin
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| Does muscle have glucagon receptors? | No
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| What is glycogen degradation in the muscle regulated by? | need for ATP and whether or not the muscle is exercising
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| What do slow twitch muscle fibers have a high capacity for? | Aerobic metabolism
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| Why do they have this capacity? | Lots of mitochondria and myoglobin
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| What is myoglobin? | Similar to hemoglobin, but only has one subunit and can only bind one oxygen.
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| Why are slow twitch muscles resistant to fatigue? | myoglobin can serve as an oxygen store
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| What are the characteristics of fast twitch fibers? | higher glycogen content, less myoglobin, fewer mitochondria
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| Which muscles will have a higher proportion of slow twitch fibers? | posture muscles psoas in back
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| What occurs in skeletal muscle during a more prolonged fast or when exposed to cortisol? | breakdown of skeletal muscle and amino acids to make glucose
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| What is one way energy in muscle cells is mobilized? | Storage of creatine phosphate
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| What is creatine? | A molecule that is synthesized in kidney, and process is completed in the liver.
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| How is creatine transported? | In the blood to skeletal and cardiac muscle cells
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| What happens once creatine gets inside the cell? | Reacts with ATP to form creatine phosphate
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| What is the previous reaction catalyzed by? | creatine kinase (creatine phosphokinase)
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| Is creatine phosphate stable? | NO. it can also undergo a nonenzymatic reaction in which it cycles to form creatine.
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| Can creatine be catabolized? | NO, it is excreted in the urine
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| What does myokinase do? | converts 2 ADP to 1 ATP and ! AMP in skeletal muscle cells
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| What is the primary way cells obtain energy at the onset of exercise? | anaerobic glycolosis
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| What does fuel usage during exercise depend on? | type of muscle fibers, length and intensity of exercise
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| What is the cycling of lactate that occurs between anaerobic tissues and the liver when anaerobic glycolysis and gluconeogenesis are occurring simultaneously called? | Cori Cycle
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| High AST can indicate liver damage? What can it also indicate? | damage to skeletal and cardiac muscle
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| What is the brain isoform of CK made of? | Two beta subunits
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| What is the skeletal muscle isoform of CK made of? | Two M subunits
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| What is that cardiac muscle isoform of CK made of? | one beta and one M subunit
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| What are some situations where you would see an elevated CK-MM level? | rhabdomyolysis, myositis, and trauma or crush injuries
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| What else will you see in elevated CK-MM cases? | elevated serum myoglobin levels
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| What are serum creatine levels and clearance rates typically used to monitor? | Kidney function
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| What is the amount of creatine produced dependent on? | muscle mass
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