Pyruvate Dehydrogenase + Citric Acid Cycle Flashcards Preview

DM Biochem > Pyruvate Dehydrogenase + Citric Acid Cycle > Flashcards

Flashcards in Pyruvate Dehydrogenase + Citric Acid Cycle Deck (21)
Loading flashcards...
1

describe the function of pyruvate dehydrogenas complex

pyruvate --------> acetyl CoA

2

describe the regulation of PDH

  • activation by phosphatase
    • dephosphorylation of PDH by PDH phosphatases
      • stimulated by Ca in skeletal muscle
      • insulin in adipocytes and liver
  • inhibition by kinase
    • by phosphorylation of PDH by PDH kinases
      • ATP, acetyl CoA, NADH
      • kinase inhibited by pyruvate

3

name the 3 bound prosthetic groups of PDH and the 2 cofactors

  • bound
    • thiamine pyrophosphate (TPP) - B1
    • lipoic acid - from octanoic acid
    • FAD - from B2
  • cofactor
    • NAD+ - from B3 (niacin)

    • coenzyme A - from B5

  • Tender Loving Care For Nancy

4

step 1 of TCA

  • condensation of aCoA and oxaloacetate to form citrate by citric synthase
    • high citrate will inhibit citrate synthase and phosphofructokinase

5

step 2 of TCA

  • citrate is isomerized to isocitrate by aconitase
    • fluoroacetate inhibits aconitase

6

step 3 of TCA

  • irreversible oxidative decarboxylation of isocitrate by isocitrate dehydrogenase
    • can be inhibited by NADH and ATP
    • stimulated by ADP and Ca
  • yields 1 NADH (1/3)

7

step 4 of TCA

  • conversion of alpha-ketoglutarate to succinyl CoA by alpha-ketoglutarate dehydrogenase
    • releases second CO2 and forms 2nd NADH (2/3)

8

step 5 of TCA

  • succinate thiokinase (succinyl CoA synthase) cleaves high energy thioester bond of succinyl CoA to yield succinate 
    • yields 1 GTP

9

step 6 of TCA

  • succinate is oxidized to fumarate by succinate dehydrogenase
    • FAD is reduced to FADH
    • competitive inhibitor of succinate dehydrogenase = malonate

10

step 7 of TCA

  • fumarate is hydrated to malate by fumarase

11

step 8 of TCA

  • malate is oxidized to oxaloacetate by malate dehydrogenase
    • 3rd NADH formed (3/3)

12

name the 3 enzymes that regulate the TCA

  1. citrate synthase
  2. isocitrate dehydrogenase
  3. alpha-KG dehydrogenase

13

describe the regulation of citrate synthase

  • irreverisble rxn
  • inhibited by its product, citrate
  • activated primarily by substrate availability, acetyl CoA and oxaloacetate

14

describe the regulation of isocitrate dehydrogenase

  • irreversible rxn
  • allosterically activated by ADP and Ca
  • inhibited by ATP, NADH

15

describe the regulation of alpha-KG dehydrogenase

  • structure similar to PDH w/ E1, E2, E3
    • 5 conenzymes required; TPP, lipoic acid, FAD, NAD, CoA
  • activated by Ca
  • inhibited by NADH and succinyl CoA

16

1 TCA cycle revolution produces:

  • 3 NADH (9 ATP)
  • 1 GTP (1 ATP)
  • 1 FADH (2 ATP)
  • = 12 ATP per acetyl CoA oxidized

17

describe thiamine deficiency

  • Low PDH activity
  • results in Werneke-Korsakoff syndrome characterized by ataxia, opthalmolplagia, memory loss, cerebral hemorrhage
  • at risk: alcoholics, malnourished individuals
  • heart failure, decrease ATP, increased cardiac ouput (wet beri-beri)

18

what are 2 other thiamine requiring enzymes?

  • alpha-ketoglutarate DH
  • branched chain a-ketoacid DH (BCKDH)

19

describe pyruvate dehydrogenase deficiency

  • metabolic effect:
    • increase in pyruvate with concomitant increase in lactic acid and alanine 
    • low production of acetly CoA
    • severe reduction in ATP production
  • clinical features:
    • lactic acidosis
    • neurologic defects: corpus callosum agenesis
    • myopathy
    • usually fatal at early age

20

describe heavy metal poisoning from disruption of pyruvate metabolism

  • arsenate, mercury and lead have high affinity for -SH
  • lipoic acid is one of the cofactors in PDH complex
    • PDH complex becomes inactive when lipoic acid is bound to heavy metals
  • CNS solely depends on glucose metabolism thorugh to oxidative phosphorylation for energy (can not use fatty acids as a fuel source) therefore effected by heavy metal poisoning

21

describe inhibitors of TCA cycle

  • fluoroacetate inhibits aconitase
    • substrate for citrate synthetase, converted to fluorocitrate which then inhibits aconitase
  • malonate inhibits succinate dehydrogenase
    • competitive inhibitor