NUTR 600 Carbs II

  1. PFK-1


    F6P--> F1,6BP

    Activated by AMP, F2,6BP (PFK2); deactivated by ATP & citrate
  2. Pyruvate kinase*
    PEP--> pyruvate

    Activated by F1,6BP (feedforward regulation)Inhibited by glucagon (cAMP) in fasting conditions. 

    *Forms ATP
  3. How is PDH regulated?1,4
    Activated by insulin --> PDH phosphatase

    Inhibited by high levels of Acetyl CoA; NADH:NAD+, ATP:ADP, PDH kinase(glucagon)
  4. Calcium
    • 1. Activates calmodulin dep glycogen phosphorylase kinase --> glycogen 'plase
    • 2. Activates isocitrate dehydrogenase 
  5. What is the sequence of electron transporters in ETC? 7

    Which ones allow protons to pass from matrix to intermembrane space? 3
    • 1. NADH dehydrogenase
    • 2. Coenzyme Q
    • 3. Cyt b
    • 4. Cyt c1 (between these two)
    • 5. cyt c
    • 6. cyt a.a.3
    • 7. O2

    (ATP synthase)
  6. What are 3 ways to inhibit ETC? 
    1. Site inhibition @ NADH dehydrogenase, cyt b-->c, cytochrome oxidase

    2. Uncouplers - increase permeability of inner mitochondrial membrane to protons and increase rate of transport of electrons w/o establishing proton gradient. Thus, energy produced can't be used for ATP synthesis and released as heat. (Aspirin) 

    3. ATP synthase (oligomyocin)
  7. What inhibit site specific areas of ETC?
    • 1. NADH dehydrogenase - barbituates
    • 2. cyt b-->c
    • 3. cytochrome oxidase - CO, H2S, cyanide 
  8. Which organs are commonly affected by mutations in mtDNA?
    skeletal muscles/brain bc of highest energy demand. 

    for example, brain is 2% of body weight, but uses 20% of energy produced when we are at rest. 
  9. Why does severity of  mitochondrial diseases vary?
    Bc mixing of mtuant DNA and normal DNA in mitochondria as they fuse with one other --> higher ratio of mutant to normal --> higher severity fo disease. 
  10. What is an example of mtDNA disease?
    exercise intolerance due to mutation of cytochrome b in muscle. 
  11. How many proteins are made by 37 genes of mtDNA?
    13 proteins --> 7 NADH dehydrogenase, 3 -->cyt c oxidase, 2 ATP synthase, 1 cytochrome b
  12. What is MELAS syndrome?
    Mitochondrial disease where infants appear normal at birth and have normal early development.

    BUT! then, there's delayed growth, vomiting, seizures, strokes due to increased number of mitochondria --> high serum & cerebrospinal fluid lactate. 
  13. Summarize cellular respiration

    Total ATP?
    • 1. Glycolysis: 6C glucose -->2 3-C pyruvates + 2 ATP + 2 NADH
    • 2. PDH: 2 3C pyruvates--> 2 Acetyl CoA + 2 NADH
    • 3. TCA cycle: 2 acetyl CoA --> 6 NADH, 2 GTP, 2 FADH2 + 4 CO2
    • 4. ETC (oxidative phosphorylation): 10 NADH + 2 FADH2 --> H2O + 34 ATP

    Total ATP: 38
  14. Where is uncoupling protein found?

    In brown adipose tissue in mitochondrial inner membrane in people & hibernating animals. 

    Purpose: thermogenesis

    FAs are oxidized to produce NADH and FADH2, but proton pump is uncoupled from ATP synthase and instead generates HEAT. 
  15. What are the 3 major pathways for glucose?
    Glycolysis, glycogenesis, and PPP (pentose phosphate pathway)
  16. What is the purpose of PPP?

    Purpose of NADPH? (3)
    Purpose: 1. Creating sugars (ribose for nucleotides, xylulose-5-P activates CHREBP) 2. Creating NADPH

    Purpose of NADPH: 1. FA/steroid synthesis 2. Regeneration of reduced glutathione 3. Detox of H2O2 in RBCs by glutathione peroxidase-glutathione reductase system.
  17. What causes glucose-6-phosphate dehydrogenase deficiency?
    Purpose: 1. Creating sugars (ribose for nucleotides, xylulose-5-P activates CHREBP) 2. Creating NADPH

    Purpose of NADPH: 1. FA/steroid synthesis 2. Regeneration of reduced glutathione 3. Detox of H2O2 in RBCs by glutathione peroxidase-glutathione reductase system. 
  18. 2 non-TCA actions of citrate?
    1. FA synthesis2. Inhibits PFK-1 (Glycolysis)
  19. What causes G6P dehydrogenase deficiency? (3)

    What does G6PD def cause?
    Oxidant drugs (AAA Antimalarials, antibiotics, antipyretics), favism - hemolytic effect of ingesting fava beans. All people w/ favism have G6PD deficiency, and infection (most common)

    Causes lack of replenishment of glutathione pool to deal with oxidative stress and preserve SH groups in RBCs -->hemolysis. 
  20. Which is the most common genetic enzyme deficiency?
    G6PD deficiency.
  21. How can G6PD def be beneficial?
    Malaria parasite can oxidize RBC NADPH from PPP for their own metabolism.

    However, infection causes a def of RBC glutathione (GSH) that is most severe in G6PD def individuals --> causing H2O2 induced hemolysis.

    This induced hemolysis blocks development of malaria parasite.

    However, after a while, malaria parasite can adapt to produce their own G6PD. 
  22. Where does GNG take place? What substrates does it use? Is this a reversal of glycolysis?
    Mostly in liver, but 40% in kidney during a lengthy fast.

    Substrates: lactate, gluconeogenenic AA, and glycerol.

    No, there are similarities, but there are also independent steps. 
  23. Under what physiological condition will GNG occur? When will it begin? When does it turn into main source? When will it peak?
    4-6 hrs after meal.

    Is main source at 16 hrs. 

    Peaks after 24 hrs
  24. What is the summary of the GNG pathway?

    Is GNG energetically costly? If so, where does energy come from?
    2 pyruvate + 4 ATP + 2 GTP + 2 NADH --> Glucose

    Yes (12 ATP). From FA oxidation. 
  25. Which are the four regulated steps in GNG?
    • 1. Pyruvate carboxylase (pyruvate --> OAA)
    • 2. PEPCK (OAA--> PEP)
    • 3. F1,6BPtase (F1,6BP--> F6P)
    • 4. G6Ptase (G6P--> Glucose)
  26. Where do substrates of GNG enter?
    • 1. Pyruvate --> directly converts to glycolysis
    • 2. Glycerol --> DHAP --> F1,6BP
    • 3. AA --> pyruvate 
  27. What regulates GNG? (5)
    • 1. Substrate availability
    • 2. Energy/Coenzyme availability (4ATP + 2 GTP + 2 NADH needed for each glucose synthesized)
    • 3. Glucagon (decreases F26BP, increases cAMP (x pyruvate kinase) and increases transcription for PEPCK/G6Ptase
    • 4. AMP - inhibits F1,6BPtase and activates PFK-1.
    • 5.Acetyl CoA - allosterically activates pyruvate carboxylase and inhibits PDH.
  28. How does glucagon affect GNG?
    • It activates GNG by
    • (1) Decreasing levels of F2,6BP (which deactivates PFK-1 and allows activation of F1,6BPtase).
    • (2) Increasing synthesis of cAMP --> inhibits pyruvate kinase, disallowing PEP --> pyruvate leading to GNG instead of TCA
    • (3) Increased transcription of PEPCK 
    • (4) increases transcription of glucose-6-phosphatase
  29. What primarily determines moment-to-moment regulation of gluconeogenesis? (2)
    Circulating level of glucagon & availability of GNG substrates
  30. What are critical steps of GNG? (4)
    • 1.Pyruvate carboxylase (pyruvate --> OAA), activated by acetyl CoA
    • 2. PEPCK (OAA-->PEP), glucagon/other signals of low energy increase mRNA/protein synthesis (transcription)
    • 3. F1,6BPtase (F1,6BP --> F6P) - inhibited by AMP, F2,6BP, activated by ATP
    • 4. Glucose 6 Ptase  (Glucose 6 P --> Glucose); transcription activated by glucagon.
  31. What occurs after a meal? (4)

    What does insulin specifically do? 9 things in 5 categories
    • 1. Glucose comes thru portal vein --> liver
    • 2. In liver, glucose --> G6P; high insulin levels
    • 3. Glycogen synthase is activated, while glycogen phosphorylase is deactivated
    • 4. Glycogenesis, glycolysis, TCA, and ETC will occur.

    Glycogenesis - PP1 activates glycogen synthase and deactivates glycogen phosphorylase; cAMP destroyed.

    Glycolysis: Insulin activates glucokinase & pyruvate kinase

    PPP: Insulin stimulates G6PD

    TCA cycle: Insulin activates PDH via PDH phosphatase

    Fats: synthesis of FAs and TAGs
  32. What happens after a meal in muscle?
    1. Glucose uptake --> glycogenesis. 
  33. What happens a while after meal? (Fasting)

    What does glucagon do? (6)
    • 1. Glucagon increases --> activates glycogen phosphorylase to start glycogenolysis. 
    • 2. Some glycolysis will still occur. 
    • 3. Lipolysis
    • 4. GNG

    Activates glycogen phosphorylase, inhibits glycolysis (glucokinase), activates lipolysis and GNG (via PEPCK/G6Ptase transcription) and activates F1,6BPtase thru destruction of F2,6BP
  34. WHat happens during exercise?

    Which is the main hormone?
    • 1. Epinephrine is main hormone, releases FAs via lipolysis --> enters liver/muscle for energy use. 
    • 2. AA/lactate/glycerol used for GNG
    • 3. Brain can use lactate
Card Set
NUTR 600 Carbs II
carb metabolism continued