Unit 4: Chapter 19 Flashcards
Each acetyl CoA enters citric acid cycle to become oxidized and loses _____ as ____
2 carbon; 2 CO2
First stage of Citric Acid cycle
- 2 carbons are introduced into the cycle by condensation of an acetyl group with a 4 carbon compound, oxaloacetate to produce 6 carbon compound of citrate
- Citrate undergoes 2 oxidative decarboxylations to releas 2 CO2
Second stage of citric acid cycle
Oxaloacetate regenerated
Both stages of citric acid cycle generate
High energy electrons that are used to power the synthesis of ATP in oxidative phosphorylation
Cellular Respiration
Glucose –> 2 pyruvate (glycolysis) –> CO2 + 2 acetyl CoA (when O2 available in mitochondria –> lose CO2 (citric acid cycle)
REMINDER: acetyl CoA can be made from glucose, fatty acids, and amino acids
Citric acid cycle produces NADH and FADH2 which is important:
- Have the power to generate ATP in later stages up to 9 ATP
- NADH = 2.5 ATP
- FADH2 = 1.5 ATP
True or False: Acetyl CoA is just produced by just glucose
False: Acetyl CoA can be produced from glucose, fatty acids, and amino acids
Where is location of Acetyl CoA formation/ pyruvate dehydrogenase complex?
Mitochondrial Matrix
Where is location of citric acid cycle?
Mitochondrial Matrix
Where is location of electron transport chian, proton pump, and ATP synthesis?
Intermembrane mitochondria
Electron Transport Chain
Membrane protein embedded in the inner mitochondria membrnae
Step 1 of Citric Acid Cycle
- Citrate synthase catalyzes condensation of oxaloacetate (4 carbon) and acetyl CoA (2 carbon) to form citryl CoA intermediate (thioester bond)
- Citryl CoA is cleaved with water to make citrate (6 carbon) and releases CoA
- Irreversible reaction
- Very negative ΔG°’
Why is step 1 of citric acid cyle irreversible reaction?
Due to thioester bond in acetyl CoA which is very high energy bond to drive reaction
Synthase
enzyme that catalyzes synthetic reaction in which two units are joined usually without the direct participation of ATP or other NTP
Citrate Synthase
- Catalyzes step 1 of citric acid cycle
- Exhibits induced fit
- Binds to oxaloacetate and conformational change occurs for formation of binding site for acetyl CoA
Formation of reaction intermediate in step 1 ______ causes a structural change that completes active site formation
Citryl CoA
Aconitase
- Catalyzes formation of isocitrate from citrate
- Switches H and OH location in order for clevage to occur and CO2 to be removed
- Tertiary alcohol to secondary alcohol
- Shuts down citric acid cycle and cellular respiration –> role as pesticide
Step 2 of citric acid cycle
- Aconitase catalyzes isomerization of citrate to isocitrate
- location of H and OH switch
Aconitase is inhibited by
metabolite of fluroacetate which acts as suicide/ irreversible inhibitor
Fluroacetate
Suicide/ irreversible inhibitor
Found in floweering plants
When ingested, turns into fluroacetyl COA which reacts with citrate to form flurocitrate
What enzyme shuts down citric acid cycle and cellular respiration and acts as pesticide?
Aconitase
What enzyme switches H and OH position?
Aconitase
Step 3 of citric acid cycle
- Isocitrate dehydrogenase catalyzes oxidative decarboxylation of isocitrate to form alpha ketoglutarate and captures high energy electron as NADH
- Isocitrate (6 carbon) oxidized to oxalosuccinate intermediate (6 carbon) and decarboxylated to alpha ketoglutarate and releases CO2 (5 carbon)
- First oxidative decarboxlation (CO2 released)
Acetyl CoA introduced 2 carbon unit but 2 carbon will not release as CO2 the ____ but _____
first time; second time
Step 4 of Citric Acid Cycle
- Alpha ketoglutarate dehydrogenase complex catalyzes the synthesis of succinyl CoA from alpha keto glutarate and generates NADH
- Second oxidative phosphorylation (releases CO2)
Alpha ketoglutarate dehydrogenase complex in step 4 of citric acid cycle is structurally and mechanically similiar to
pyruvate dehydrogenase complex
In first time of citric acid cycle, the 2 carbon that are released are from where?
Oxaloacetate
Alpha ketoglutarate dehydrogenase complex cofactors
TPP, Lipoic acid, FAD, coenzyme A, Mg2+
Step 5 of Citric Acid Cycle
- Succinyl Coa synthetase catalyzes clevage of thioester linkage of Succinyl CoA and powers formation of ATP and forms succinate
- Only step ATP generated
- Only substrate level phosphorylation in cycle
Suiccinyl CoA product of step 4 contains
thioester bond so compound has high phosphoryl transfer potential
Substrate phosphorylation
High phosphoryl transfer potential compound donates phosphate to ADP for ATP formation
What step of citric acid cycle is only step ATP generated and substrate level phosphorylation?
Step 5: Succinyl CoA to Succinate
Reaction Mechanism of Succinyl CoA synthetase
- Histidine active site of Succinyl CoA synthetase performs nucleophillitic attack on Succinyl phosphate for succinate to be released
- Hydrolysis of thioester bond to produce ATP
What steps are invovled in regeneration of Oxaloacetate?
Steps 6, 7, 8
_____ regenerates each citric acid cycle
Oxaloacetate (4 carbon)
___ and ___ initiates another citric acid cycle
Oxaloacetate; acetyl CoA
All enzymes in citric acid cycle are found in _____ but for sucinate dehydrogenase (step 6)
mitochondrial matrix
All enzymes in citric acid cycle are found in mitochondrial matrix but for ___________
Succinate Dehydrogenase (step 6) embedded in innermitochondrial membrane
Step 6 of citric acid cycle
- Catalyzed succinate dehydrogenase
- Succinate oxidized to Furmate
- FAD reduced to FADH2
- NOT IN MITOCHONDRIAL MATRIX, in innermitochondria membrane
Step 7 of citric acid cycle
- Catalyzed by furamase
- Furmate added water for double bond to form hydroxyl and hydrogen on maltate
Step 8 of citric acid cycle
- Catalyzed by maltate dehydrogenase
- Maltate oxidized to Oxaloacetate
- NAD+ reduced to NADH
- Fourth and final oxidation of cycle
- Very positive ΔG°’
- Very negative ΔG
- Rxn pulls citrate synthetase reaction of the next step
From glucose, what are the products of the citric acid cycle
6 NADH, 2 FADH2, 4 CO2, 2 ATP
Products are doubled starting from glucose as we have 2 acetyl CoA
Net reaction of Citric Acid Cycle with 1 acetyl CoA
1 acetyl CoA + 3 NAD+ + FADH + ADP + Pi + 2H20 –> 2CO2 + 3NADH + FADH2 + ATP + 2H+ + CoA
Per pyruvate generates what and ATP equivalents
4 NADH = 10 ATP
1 FADH = 1.5 ATP
1 ATP
Total 12.5 ATP per pyruvate
How mcuh ATP is generates from glucose through acetyl CoA formation and citric acid cycle?
25 ATP
What is key control point in citric acid cycle?
Isocitrate dehydrogenase and alpha ketoglutarate dehydrogenase
Citric Acid Cycle must be reeplineshed because
Citric Acid cycle provides precursors for biosynthesis so replenishing reactions are needed (anaplerotic)
Anaplerotic reactions refers to
Replening reactions
Prominent anaplerotic reaction is catalyzed by ______ ________
pyruvate carboxylase
Glyoxylate Cycle
- Similiar to citric acid cycle but bypass 2 decarboxylation steps, allowing synthesis of carbohydrates from fats
- Not in humans
- Succinate can be converted into oxaloacetate and into glucose since no carbon is loss
- prominent in oil rich seeds
Pyruvate carboxylase anaplerotic reaction
Increase in Acetyl CoA activated pyruvate carboxylase which activates oxaloacetate for repinish
Key enzymes of glyoxylate cycle
Isocitrate lyase: catalyzes cleavage of isocitrate to glyoxylate and succinate
Maltate synthase: catalyzes reaction of glyoxylate with acetyl CoA to produce maltate
Reaction equation of glyoxylate cycle
2 acetyl CoA + NAD+ + 2H20 –> succinate + 2 COASH + NADH + 2H+
NO CO2 produced!!
One extra oxaloacetate