Exam 2 Lecture 19 Citric Acid Cycle Flashcards
TCA takes place where?
Inside the mitochondria
TCA cycle does what to carbon fuels?
Oxidizes carbon fuels for harvesting high energy electrons
T/F: TCA cycle is amphibolic
True performs catobolism and anabolism
T/F: TCA cycle is not a source of precursors for biosynthesis
False. Is a source for biosynthesis
TCA stands for:
Tricarboxylic acid cycle
What are the high energy e- carries of the TCA cycle?
NADH
FADH2
GTP
Oxidative phosphorylation happens in :
Mitochondria
ATP production:
1 NADH = _ ATP
1 FADH2 _ ATP
1 GTP = _ ATP
1 NADH = 2.5 ATP
1 FADH2 = 1.5 ATP
1 GTP = 1 ATP
What are types of energy nutrients that will be degraded for the TCA cycle?
Fats, polysaccharides, and proteins
Oxidation of 2-carbon units produce:
- 2 CO2 molecules
- 1 GTP
- high energy e-s in the form of NADH and FADH2
Acetyl CoA is the activated form of:
Acetate
Acetyl CoA is obtained from what 3 energy nutrients?
- Carbohydrates (glucose oxidized into 2 pyruvate, 2 pyruvate decarboxylation into 2 acetyl CoA)
- Lipids (TAG beta-oxidation into acetyl CoA)
- Proteins (breakdown into various amino acid and converted to acetyl CoA)
What are the 3 steps of pyruvate to acetyl CoA
- Decarboxylation (CO2 removed)
- Oxidation (2 e- leaving)
- Transfer acetyl group to coenzyme A
T/F: In converting pyruvate to acetyl CoA, reactions are coupled to preserve energy to drive formation of NADH and acetyl CoA
True
Pyruvate utilizes _ to enter the mitochondria
Mitochondrial pyruvate carrier (MPC)
What enzyme catalyzes the decarboxylation of pyruvate?
Pyruvate dehydrogenase complex (PDC)
What are the 3 enzymes required for the pyruvate dehydrogenase reaction
E1, E2, E3
What are the coenzymes for the pyruvate dehydrogenase reaction
- TPP
- Lipoic acid
- FAD
- CoA
- NAD+
Of the 5 coenzymes for the pyruvate dehydrogenase reaction, which are the catalytic cofactors?
TPP
Lipoic acid
FAD
Of the 5 coenzymes for the pyruvate dehydrogenase reaction, which are stoichiometric cofactors?
CoA
NAD+
PDC/PDH is regulated via
Allosteric interactions and reverse phosphorylation
Hight amounts of acety CoA directly inhibits _
PDH/C complex subunit E2 ie increases phosphorylation (kinase) to inactivate PDH/PDC
Accumulation of ADP and pyruvate activates _
Phosphatases ie active PDH/PDC
What is the common currency for the TCA cycle?
acetyl CoA
PDH links _ to the citric acid cyle (TCA)
Glycolysis
What enzyme is used for the 1st step to catalyze condensation of: 4-carbon OAA to citrate?
Citrate synthase
The hydroxyl group on citrate is not in the proper location for oxidative decarboxylation. What enzyme and its mechanism to form isomerize citrate into isocitrate?
Enzyme aconitase via dehydration/hydration moves OH atoms (uses iron-sulfur cluster)
What is the rate limiting step in the TCA cycle?
Enzyme isocitrate dehydrogenase forms alpha-ketoglutarate
Rate limiting step in TCA cycle is the first of what?
First of 4 oxidation-reduction reactions
What is the unstable intermediate formed by oxidation-reduction of isoctirate
Oxalosuccinate (loses CO2 while bound to the enzyme isocitrate dehydrogenase)
What enzyme takes alpha-ketoglutarate and forms succinyl CoA
Alpha-ketoglutarate dehydrogenase
What is the mechanism of alpha-ketoglutarate dehydrogenase
Decarboxylate an alpha-ketoacid and creates a thioester linkage with CoA
Enzyme used for succinyl CoA into succinate
Succinyl CoA synthetase
Succinyl CoA synthetase is the only step that directly yields:
A high energy phospho-transfer compound (GTP, ATP)
Succinyl CoA synthetase yields 2 isozymic forms ie:
- In tissues that perform many anabolic reactions (liver) yields Succinate + CoA + GTP
- In skeletal and heart muscle that perform large amounts of cellular respiration yields Succinate + CoA + ATP
Enzyme used for Succinate to Fumarate
Succinate dehydrogenase
Succinate dehydrogenase catalyzes formation of fumarate while generating
FADH2 (high energy substance)
Succinate dehydrogenase is located in the _
Inner mitochondrial membrane directly associated with ETC Complex II
FADH2 is not released from succinate dehydrogenase but instead e-s are passed directly to _ in the ETC
Co-Q
What enzyme is used to catalyze Fumarate into malate
Fumarase via hydration of fumarate to form L-Malate
What enzyme catalyzes the final step of the TCA cycle: Malate into OAA
Malate dehydrogenase
Oxidation of malate has a positive _
Standard free energy
NADH inhibits _
PDH/C complex subunit E3
Phosphatases are also stimulated by _ which increases to initiate muscle contraction
Ca2+
Insulin can stimulate FA synthesis via
Activating phosphatases and increasing the conversion of pyruvate to acetyl CoA
What is the first regulation site in the TCA cycle?
Citrate synthase prevents the wasteful hydrolysis of acetyl CoA
What is the 2nd regulatory site in the TCA cycle?
Isocitrate dehydrogenase allosterically stimulated by ADP enhances enzyme affinity for substrate. NADH also inhibits by directly displacing NAD+
What is the 3rd control site in the TCA cycle?
Alpha-ketogluturate dehydroenase allosterically inhibited by its products: succinyl CoA and NADH
Control at isocitrate dehydrogenase leads to build up of citrate which can transport to the cytosol and signal _
Phosphofructokinase and halt glycolysis
Control of alpha-ketogluturate dehydrogenase leads to build up of alpha-ketogluturate that can be used for _
Synthesis of amino acids and purine bases
Why is the TCA cycle anaplerotic?
Uses and produces certain substrates; provides intermediates for replenishing TCA cycle
What are the 2 major anaplerotic reactions?
- Degradation of amino acids
2. Carboxylation of pyruvate
When energy needs are met, intermediates are used for _ and are replenished by formation of _
Used for biosynthesis of other molecules and replenished by formation of OAA from pyruvate
OAA biosynthesis into
Glucose
aspartate -> other amino acids, purines, and pyrimidines
Citrate biosynthesis into
Fatty acids and sterols
Alpha-ketoglutarate biosynthesis into
Glutamate -> other amino acids -> purines
Succinyl CoA biosynthesis into
Porphyrins, heme, chlorophyll
T/F: GTP biosynthesis from substrate level phosphorylation
True
T/F: TCA cycle oxidized 3-carbon units
False 2-carbon unites
Anaplerotic reactions are required during states of _
Low energy
T/F: PDH/C is regulated both allosterically and by phosphorylation
True
T/F: TCA cycle is a source of biosynthetic precursors
True
Pyruvate carboxylase is one of the most important anaplerotic enzymes bc
Forms OAA from pyruvate (C3->C4); formation of new bond requires ATP and cofactor biotin; activated by acetyl CoA
*distinct from PDC