citric acid cycle

What is a major purpose of aerobic catabolism?

to capture the energy in biological fuel molecules and use it to make ATP

Where does CAC occur?

matrix

CAC oxidizes the in acetyl-CoA. __ carbons atoms converted to 2 ___.

acetate; 2; CO2

the CAC starts and ends with?

oxaloacetate (OAA)

CAC happens times per glucose.

2

What is the CAC the final stage of?

aerobic catabolism of carbohydrates, fatty acids, and amino acids

What is the result of the complete oxidation of glucose?

2C lost as CO2 from PDC
4C lost as CO2 from CAC

The CAC is an pathway. Meaning?

amphibolic. used in both catabolic and anabolic processes

What does the amphiboliic nature of the CAC depend on?

cellular conditions:
-oxidation of fuel molecules
-synthesis of metabolic intermediates

Acetyl-CoA (C2) condenses with ___- to make _____.

oxaloacetate (C4); citrate (C6)

During the CAC, 2 carbons are ___- as ___.

lost; CO2

What is regenerated during the CAC?

oxaloacetate

What are the products of the CAC that leave the CAC?

-2 CO2
-3 NADH
-1 FADH2
-1 GTP

What do the two oxidative decarboxylation steps make?

1 NADH and 1 CO2 per step

What does the SLP step make?

1 GTP

What do the oxidation steps make?

one makes FADH2, the other makes NADH

What do NADH, FADH2, and GTP have in common?

-products of the CAC
-high energy

How many energy capture steps are there?

5. steps 3, 4, 5, 6, 8

How many regulated enzymes are there?

3. step 1, 3, 4

What is the step 1 enzyme?

citrate synthase

What is the first step of the CAC?

-Acetyl CoA adds its 2 carbon acetyl group to oxaloacetate producing citrate
-energy comes from breaking thioester bond with H2O
-step 1: OAA + A-CoA -> Citroyl-CoA
-step 2: citroyl-CoA + H2O -> citrate + HSCoA

What is the step 2 enzyme?

aconite

What is the second step of the CAC?

-simple isomerization
-citrate to isocitrate
-converted from a tertiary alcohol to a secondary alcohol, which is easier to oxidize to a carbonyl

What is the step 3 enzyme?

isocitrate dehydrogenase

What is the third step of the CAC?

Isocitrate is oxidised, reducing NAD+, the resulting compound looses a CO2 molecule, forming a-keto-glutarate
-irreversible, regulated
-no proton is released because it is given to CO2
-oxidative decarboxylation

What is the step 4 enzyme?

alpha-ketoglutarate dehydrogenase

What is the fourth step of the CAC?

CO2 is lost again, and the left over compund is oxidised once more (releasing NADH). The remaining molecule is attatched to CoA, forming SuccinylCoA
-oxidative carboxylation
-transfer of C4 to CoA

• similar to PDC

What are the similarities between PDC and alpha-ketoglutarate dehydrogenase?

-oxidation
-decarboxylation
-formation of a thioester

What are the differences between PDC and alpha-ketoglutarate dehydrogenase?

-PDC: transfer of C2 to CoA
-alpha-ketoglutarate dehydrogenase: transfer of C2 to CoA
-alpha-ketoglutarate dehydrogenase is regulated only by allostery, PDC is also regulated by phosphorylation

What is the difference between a synthase vs a synthetase?

synthetase indicates a nucleoside triphosphate is involved in the reaction

What is the step 5 enzyme?

succinyl-CoA synthetase

What is the fifth step of the CAC?

the CoA is lost, GTP and Succinate are formed
-break thioester bond and form phosphoanhydride bond
-SLP reaction

What are the two steps of the fifth step of the CAC?

step 5a: succinyl-CoA (thioester) converted to succinyl phosphate (mixed anhyride) and CoA released
step 5b: succinyl phosphate (mixed anhydride) converted to succinate (phosphoanhydride) which is an SLP

What generates the GDP for the succinyl-CoA synthetase reaction?

-nucleoside diphosphate kinase (NDK)
-moves phosphates
-reversible, nonspecific
-GTP + ADP -> GDP + ATP (phosphates are moved)

What is the step 6 enzyme?

succinate dehydrogenase

What is the sixth step of the CAC?

2 hydrogens are given to FAD, forming FADH2 and oxidising succinate to make fumarate

What is unique about succinate dehydrogenase?

it is also part of oxidative phosphorylation (complex III), uses FADH2 which is a phosphate group

What is the step 7 enzyme?

fumarase

What is the seventh step of the CAC?

-addition of H2O converts fumarate to malate
-hydration reaction

What is the step 8 enzyme?

malate dehydrogenase

What is the eighth step of the CAC?

Malate is oxidised and oxaloacetate is reformed. NAD+ converted to NADH

What do they last three reactions of the CAC do?

convert a methylene group of succinate to a carbonyl group in OAA

What is the general sequence from the CAC that is also seen in the oxidation of fatty acids?

-dehydrogenation to generate a carbon-carbon double bond (FADH2 generated)
-hydration of carbon-carbon double bond
-oxidation of an alcohol to a carbonyl group (NADH generated)

How is FADH2 reoxidized?

donates electrons to Q, a mobile electron carrier

QH2 is reoxidized by in the ETC.

complex III

Succinate dehydrogenase is?

a membrane bound enzyme and is part of complex II in the ETC

CAC is only a true cycle when in _ mode.

catabolic

Q is a prosthetic group for which proteins?

None, it is a cosubstrate

How is isocitrate dehydrogenase regulated?

-allosterically activated by ADP
-allosterically inhibited by ATP
-allosterically inhibited by NADH

How is alpha-ketoglutarate dehydrogenase regulated?

-allosterically activated by Ca2+
-allosterically inhibited by succinyl-CoA (product)
-allosterically inhibited by NADH

What is an anaplerotic reaction?

a reaction that replenishes a citric acid cycle intermediate

What are the two anaplerotic reactions?

-amino acid breakdown
-pyruvate carboxylase

What is the reaction catalyzed by pyruvate carboxylase?

pyruvate + CO2 + ATP + H2O -> oxaloacetate + ADP + Pi + 2H+

Pyruvate carboxylase is ___ by acetyl-CoA.

allosterically activated

PDH complex is inhibited by?

acetyl CoA

What are the functions of the CAC?

• Provide biosynthetic precursors
• An important step in the generation of ATP for cellular needs.
• CAC generates ~10 ATP for each acetyl-CoA (2 acetyl-CoA per glucose).

complete aerobic oxidation of glucose yields a net of _ ATP. What are the sources of ATP?

32. 2 from glycolysis. 5 from PDC (via NADH). 20 from CAC (16 via NADH, 3 via FADH2, 2 via GTP)

Anaerobic glycolysis generates ATP from glucose and _ ATP from glycogen.

2; 3

Oxidation of lactate produces how many ATP?

15

How much water is generated by the ETC from the oxidation of lactate?

6 H2O

How much water is generated by the ETC from the oxidation of glucose?

12 H2O. 10 NADH (2 GAPDH, 2 PDC, 6 CAC) and 2 GADH2 (CAC)

How much water is generated by the ETC from the oxidation of glucose under anaerobic conditons?

none

A major driving force in the regulation of aerobic metabolism is the relative concentration of _.

ADP in the matrix

Oxygen consumption in the presence of an uncoupler.

increases

What is uncoupling?

-electron transport occurs with reduced ATP synthesis
-proton gradient dissipated faster
-rate of electron transport increases (O2 consumption increases)
-rate of re-oxidation of reduced electron carriers increases
-rat of reactions in the CAC increases
-catabolic pathways are active

All pathways are __.

exergonic