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Biochem Block 2 > TCA cycle > Flashcards

TCA cycle Flashcards

1
Q

Different names for TCA cycle

A
  • krebs cycle

- citric acid cycle

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2
Q

TCA cycle definition

A

-the final pathway where the catabolism of carbohydrates, amino acids, and fatty acids (inorganic molecules) converge and their carbon skeletons are converted to CO2

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3
Q

Interactions with catabolic pathways

A

-the breakdown of some amino acids provides certain TCA cycle intermediates

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4
Q

Interactions with anabolic pathways

A
  • some TCA cycle intermediates feed into biosynthetic pathways
  • synthesis of certain amino acids
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5
Q

ETC interactions

A
  • TCA cycle provides energy carried by NADH and FAD2 for the production of ATP in the ETC
  • ETC couples reduced carriers with ATP by ovidative phosphorylation
  • TCA cycle located in mitochondrial matrix to be close to the ETC
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6
Q

Linear metabolic pathway VS cycle

A
  • linear: Starts with one metabolite and ends with a different one (glycolysis)
  • cycle: Starts with a certain metabolite that undergoes certain steps to form different intermediates, but in the end the same metabolite is regenerated and there is no net loss or gain of intermediates
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7
Q

Oxidative decarboxylation of pyruvate

A
  1. pyruvate transferred into the mitochondria by mitochondrial pyruvate carrier or simple diffusion
  2. converted into acetly coA by pyruvate dehydrogenase complex (PDH)
  3. 1 carbon is released as CO2 and NADH is produced
  4. IRREVERSIBLE STEP
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8
Q

PDH structure

A
  • protein aggregate of 3 enzymes (E1, E2, E3)
  • five different coENZYMES(organic)
  • Thiamine pyrophosphate (TTP): from thiamine and vitamin B1
  • Lipoamide(requires lipoic acid)
  • CoA(pantothenic acid and vitamin B5)
  • FAD(riboflavin and vitamin B12)
  • NAD+(nicotinamide, vitamin B3/niacin)
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9
Q

Regulation of PDH

A
  • phosphorylation deactivates (PDH kinase)
  • dephosphorylation activate(PDH phosphatase)
  • pyruvate inhibits kinase, so activater
  • NAD+,ADP,Ca2+,CoA=activates
  • acetyl coA, NADH, ATP=deactivate

“regulated by substrate activation and product inhibition”

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10
Q

Step 1: synthesis of citrate from acetyl coA and oxaloacetate

A
  • reaction of condensation 2 carbons molecule fuses with a 4 carbon molecule to form 6-CARBON CITRATE
  • citrate is a precursor for fatty acid synthesis and an inhibitor for PFK-1 in glycolysis
  • enzyme: Citrate Synthase
  • regulation: substrate activation or product inhibition
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11
Q

Step 2: Isomerization of Citrate

A

Enzyme: Aconitase

  • reversible
  • iron-sulfur protein
  • inhibited by fluoroacetate (results in a build up of citrate so its a suicide inhibitor)
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12
Q

Step 3: Oxidative dearboxylation of isocitrate

A

-IRREVERSIBLE STEP
-RATE LIMITING
-yields first NADH
-releases 1 CO2
Enzyme: isocitrate dehydrogenase
-regulation: allosterically
-ATP and NADH INHIBIT
-ADP and Ca2+ ACTIVATE

“regulation by energy status of the cell”

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13
Q

Step 4: Oxidative decarboxylation of alpha-ketoglutarate

A

-IRREVERSIBLE STEP
-yields the second NADH
-releases 1 CO2
Enzyme: alpha-ketogutarate dehydrogenase complex
-3 different enzymes
-Same coenzymes required as PDH
Regulation:
-inhibited by its products
-activated by Ca2+

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14
Q

Vitamin deficiencies

A
  • alpha-ketoglutarate dehydrogenase complex and PDH require multiple coenzymes derived by vitamins
  • deficiency of niacin or thiamine can cause central nervous system problems
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15
Q

Arsenic poisoning

A
  • alpha-ketoglutarate dehydrogenase and PDH both require lipoic acid
  • arsenic poisoning forms a stable thiol with the group in lipoic acid making it unavailable to serve as a coenzyme
  • neurological disturbances and death
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16
Q

Step 5: Cleavage of succinyl CoA

A

-cleaves high energy thioester bond
-coupled with phosphorylation of GDP-GTP(substrate level phosphorylation)
-GTP—->ATP
-releases CoA
Enzyme: succinate thiokinase

17
Q

Step 6: Oxidation of succinate to fumerate

A

-2 H atoms are transferred to FAD to produce FADH2
-reversible
Enzyme: succinate dehydrogenase
-directly embedded in the inner mitochondrial membrane (complex 2 of ETC)
-direct transfer of electrons

18
Q

Step 7: Hydration of fumarate

A

-freely reversible step
Enzyme: fumarase
(produces malate which is also found in urea, purine synthesis, and phe an tyr catabolism

19
Q

Step 8: Oxidation of Malate

A

-final step that regenerates OAA
-positive free energy change(+deltaG)
-driven by highly favorable reaction after this step of acetyl coA to citrate
-produces final NADH
Enzyme: malate dehydrogenase
(OAA also produced by transamination of aspartic acid)

20
Q

Summary of TCA cycle

A
  • 2 C-atoms enter the cycle
  • 2 CO2 are released
  • NO NET CONSUMPTION OR PRODUCTION OF OAA OR OTHER INTERMEDIATES
  • 3 NADH are produced
  • 1 FADH2 is produced
  • 1 GTP is produced by substrate level phosphorylation
21
Q

Energy produced

A 
Substrate level phosphorylation
-Glycolysis: 2 ATP
-TCA: 1 GTP=1 ATP(2)
Oxidative phosphorylation
-Glycolysis: 2 NADH=6 ATP
-TCA:11 ATP(2)
-PDH:1 NADH=3 ATP(2)

TOTAL: 36-38 ATP

22
Q

Name the irreversible steps

A
  1. citrate synthesis
  2. isocitrate dehydrogenase
  3. alpha-ketoglutarate dehydrogenase

regulation:

  • energy status of the cell inhibits
  • calcium released from muscles activates

Biochem Block 2 (11 decks)

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