TCA cycle Flashcards
What is required for nucleic acid synthesis?
Requires a precursor from carbohydrate source (PIPP)
and a precursor from proteins
b-oxidation of fat yields _
b-oxidation of fat yields Acetyl-CoA
Apart from fats, what is another substance that yields Acetyl-Coa?
Some AA (e.g. Leucine, Threonine etc)
How can pyruvate be converted to Acetyl-CoA?
Oxidative decarboxylation by a large enzymatic complex- pyruvate dehydrogenase complex
Describe Oxidative decarboxylation
Purpose
Irreversible/reversible
Products
Converts pyruvate to Acetyl-CoA
It is irreversible
Makes NADH
Can mammals convert Acetyl-CoA to pyruvate?
No
Describe PDC
PDC – cluster of multiple copies of three enzymes
- Pyruvate dehydrogenase (E1), - Dihydrolipoyl transacetylase (E2)
- Dihydrolipoyl dehydrogenase (E3)s
Converts pyruvate to Acetyl-CoA
Steps of how pyruvate is turned into Acetyl-CoA
Step 1: pyruvate is taken up by a prosthetic arm - thiamine pyrophosphate (TPP) of pyruvate dehydrogenase (E1), undergoing decarboxylation to the hydroxyethyl derivative- carboxyl group is removed as CO2
Step 2: TPP moves and transfers hydroxyethyl group to another prosthetic arm on dihydrolipoyl transacetylase (E2) - lipoyllysyl. Attachment of the backbone of pyruvate turn lipoyllysine to an Acyl lipoyllysine which is attached to lysine amino acid on E2 enzyme.
Step 3: CoA group gets attached to pyruvate backbone to yield acetyl-CoA and the fully reduced (dithiol) form of the lipoyl arm which cannot accept the pyruvate arm coming in, so it has to be oxidized by removing hydrogens.
In step 4 dihydrolipoyl dehydrogenase (E3) promotes transfer of two hydrogen atoms from the reduced lipoyl arm of E2 to the FAD prosthetic group of E3, restoring the oxidized form of the lipoyllysyl group of E2.
In step 5 the reduced FADH2 of E3 transfers a hydride ion to NAD+, forming NADH. The enzyme complex is now ready for another catalytic cycle.
Once Acetyl CoA is available (from __, __), it can enter _
Once Acetyl CoA is available (from b-oxidation, AA metabolism), it can enter TCA cycle
Acetyl group of pyruvate is transferred to __
Acetyl group of pyruvate is transferred to CoA-SH
TCA: _ intermediates _ enzymes (steps) Acetyl-CoA donates _ carbons to _ carbon compound (oxaloacetate)
TCA: 9 intermediates 8 enzymes (steps) Acetyl-CoA donates 2 carbons to 4 carbon compound (oxaloacetate)
List the intermediates of TCA
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C - citrate I - isocitrate K - a-ketoglutarate S - succinyl CoA S - succinate F - fumarate M - malate O - oxaloacetate
List the enzymes for TCA
Can Anthony Drink Down Seven Drinks 'Fore Death C- Citrate synthase A- Aconitase D- Isocitrate dehydrogenase D-α-ketoglutarate dehydrogenase[edit] S- Succinyl coenzyme A synthetase DS- Succinate dehydrogenase F- Fumarase De- Malate dehydrogenase
In order for TCA to continue, __ has to interact with __
In order for TCA to continue, oxaloacetate has to interact with incoming Acetyl- CoA
How many dehydrogenases are there in TCA cycle?
4
How many irreversibel reactions are there in TCA cycle?
3
How does Acetyl-CoA enter the TCA?
Acetyl-CoA enters the TCA carrying 2 carbons which are donated to 4 carbon compound oxaloacetate which now enters the cycle as citrate
What does Acetyl-CoA contribute to in TCA?
Two carbon atoms of Acetyl-CoA are converted to CO2
Two carbons of Acetyl-CoA do not contribute to CO2 in the first pass!!!
2Co2 come from 3rd and 4th reaction catalyzed by isocitrate dehydrogenase and a-ketoglutarate dehydrogenase
Which step produces ATP in TCA
What’s special about it?
Succinyl-CoA synthetase converts succinyl-CoA to succinate
- It uses ATP as it is a synthetase when in converts succinate to succinyl-Co
In TCA in does an opposite reaction-> generates ATP or GTP
There are 2 isoforms of Succinyl-CoA synthetase- one generates GTP one generates ATP
Either of those can be a part of TCA cycle
Acetyl-CoA = _CO2 + _ NADH + _ FADH2 + _ ATP
Acetyl-CoA = 2 CO2 + 3 NADH + 1 FADH2 + 1 ATP
Amphibolic meaning
Both catabolic and anabolic
Anaplerotic meaning
replenishing reactions
Describe anaplerotic reactions
- Pyruvate to oxaloacetate +ADP +Pi in Liver, kidney. By pyruvate carboxylase
- Phosphoenolpyruvate to oxaloacetate in Heart, skeletal muscle. By PEP carboxylase
- Phosphoenolpyruvate to oxaloacetate by PEP carboxylase in Higher plants, yeast, bacteria
- Pyruvate to malate by malic enzyme. Widely distributed in eukaryotes and bacteria
Alternative reaction for oxaloacetate apart form TCA
Oxaloacetate-> PEP -> Gluconeogenesis
How do AA contribute to gluconeogenesis?
Oxaloacetate is the one that ultimately enters the gluconeogenic pathway. This is how AA can contribute to gluconeogenesis
Oxaloacetate can also be used for synthesis of AA - can be taken out
In TCA, enzymes of __ reactions are regulated. Name them
In TCA, enzymes of irreversible reactions are regulated:
citrate synthase, isocitrate dehydrogenase and α-ketoglutarate dehydrogenase
How’s PDH of TCA regulated?
PDH is phosphorylated on E1
enzyme – inactivated
How are the irreversible reaction of TCA regulated?
By allosterically regulating th enzymes
Citrate synthase- + effector: ADP; - effector: ATP, NADH,
Citrate, Succinyl CoA
isocitrate DH: + effector: ADP; - effector: ATP, NADH
α-ketogluterate DH: - effector: ATP, NADH, Succinyl CoA
Intermediates of the TCA cycle serve as precursors for _
Intermediates of the TCA cycle serve as precursors for biosynthesis of biomolecules
Anabolic reaction of oxaloacetate
Oxaloacetate is another α-keto acid and its transamination leads to aspartate and other amino acid biosynthesis.
Oxaloacetate is also the precursor of purines and
pyrimidines via aspartate
Anabolic reaction of citrate
Fatty acids and sterols are synthesized from citrate
Anabolic reaction of succinyl CoA
Porphyrins and heme are synthesized from succinyl CoA
Anabolic reaction of α-ketoglutarate
Many aminoacids are synthesized starting with
transamination of α-ketoglutarate
Anaplerotic reaction of oxaloacetate
It is replenished from pyruvate by the gluconeogenic enzyme pyruvate carboxylase:
Pyruvate + CO2 + ATP + H2O -> Oxaloacetate + ADP + Pi
Which ion activates TCA?
Ca2+
Do FAs contribute to gluconeogenesis?
Acetyl-CoA cannot be converted to Pyruvate
Odd number FA metabolism ultimately produces a 3 carbon compound-> succinate
C14-tracer experiments show flow of carbon from FA to glucose
When there’s accumulation of Acetyl-CoA-> ketogenesis takes place
Acetone is expired through breath , but…
- Acetone loss through breath accounted for 2-30%
- 60% ended up in glucose v - Acetone can be converted to glucose through 2 intermediates- thus acetone can contribute to gluconeogenesis
Acetone is a ketone body made of acetyl-coA
Acetyl- CoA come from fatty acids-> fatty acids contribute to glucose
What is coenzyme Q? WHat does it do?
One of electron carriers which is called ubiquinone or ubiquinol, depending on it’s oxidation state
It is a mobile electron carrier- moves in the intermembrane space of mitochondria
As it is mobile it picks up electrons from complex I and II. Brings it to complex III
Ubiquinone is _
Ubiquinol is _
Ubiquinone is fully oxidized so it doesn’t’ have hydrogen ions
Ubiquinol is fully reduced
Name electron carriers
Heme/Cytochrome C
Iron sulfur centers
Ubiquinone (Q) is the point of entry for electrons derived from ___
Ubiquinone (Q) is the point of entry for electrons derived from reactions in the cytosol, from fatty acid oxidation, and from succinate oxidation (in the citric acid cycle).
How do electrons from NADH get to ubiquinone?
Electrons from NADH pass through a Fe-S centers (in Complex I) and then to ubiquinone-> ubiquinol .
How do electrons from succinate get to ubiquinone?
Complex II is succinate dehydrogenase - converts succinate to fumarate. Electrons from succinate pass through a flavoprotein with the cofactor FAD and several Fe-S centers which then give it to ubiquinone-> ubiquinol
How do electrons from G3P get to ubiquinone?
Glycerol 3-phosphate donates electrons to a flavoprotein (glycerol 3-phosphate dehydrogenase) on the outer face of the inner mitochondrial membrane, from which they pass to Q.
How do electrons from Acetyl-CoA get to ubiquinone?
Acyl-CoA dehydrogenase (the first enzyme of b-oxidation) generates FADH2 which can donates its electrons to ubiquinone-> ubiquinol
Which electron transport chain complex is the biggest/ Why?
Complex I
Coated by 43 different genes coming from both nuclear genome and mitochondrial genome
Describe the passage of electrons through complex I
NADH along with hydrogen provides 2 electrons to complex I that ultimately go to ubiquinone-> ubiquinol
In the process this complex also expels 4 hydrogens out into the intermembrane space-accumulation of hydrogens
2 Hydrogens go to ubiquinone-
2 hydrogens go to intermembrane space
What is the other name for complex I
NADH : ubiquinone oxidoreductase
What is the reaction formula for complex I
NADH+Q+5H+N =NAD+ +QH2 +4H+P
Describe complex II
Function
Parts
It is actually “Succinate dehydrogenase”
- Converts Succinate to Fumerate (FADH2) v FAD acts as a co-factor
- Several Fe-S centers are also present through which electrons are carried to be eventually given to ubiquinone-> ubiquinol
- Reduces Q (Ubiquinone) to QH2 (Ubiquinol)
- No H+ moves out across the membrane
Oben big difference between complex I and II
there are no additional hydrogens being thrown out in complex II
