TCA Cycle (midterm) Flashcards
Only 10% of the energy contained in the glucose molecule is extracted by glycolysis. So approx 90% of the biologically available energy in the molecule remains in ____________
pyruvate
The TCA cycle oxidizes acetyl CoA to….
CO2 and H2O
The TCA cycle generates _______ ATP per pyruvate or ______ ATP per acetyl Co-A
15, 12
What enzyme is used to convert pyruvate into acetyl CoA? What is this reaction called?
pyruvate dehydrogenase (PDH)
Oxidative decarboxylation rxn
this rxn is known as pyruvate oxidation
it forms a CoA thioester
Where is PDH located?
in the mitochondria
What 5 coenzymes are required to convert pyruvate to acetyl CoA?
1) thiamine pyrophosphate
2) lipoate
3) CoA
4) FAD
5) NAD+
mnemonic: Tender loving care for Nancy
What is the only irreversible step in the human body?
pyruvate to acetyl CoA
What effect does alcohol have on glucose metabolism?
-chronic alcoholics tend to be hypoglycemic and suffer from lactoacidosis (bc pyruvate can only convert to lactate in this case)
-chronic alcoholics frequently have a thiamine deficiency, which leads to a non-functional PDH
-infusing glucose and thiamine corrects the hypoglycemia
-the intermediate acetaldehyde is extremely toxic
What 4 enzymes require these 5 coenzymes:
1) thiamine pyrophosphate
2) lipoate
3) CoA
4) FAD
5) NAD+
(Tender loving care for Nancy)
1) PDH
2) alpha KG DH (from TCA)
3) branch chain ketoacid DH (in the catabolism of branched chain AA) (if this is deficient= maple syrup urine disease)
those 3 enzymes are all located in mitochondrial matrix
4) transketolase (catalyzes the rxn of ribose 5 phosphate to other sugars in the PPP pathway and is located in the cytoplasm)
What are the other names for TCA cycle?
-cyclic acid cycle
-citric acid cycle
-citrate cycle
-krebs cycle
its called this bc citrate has 3 carboxyl groups
What is the substrate for the TCA cycle?
acetyl CoA
How many carbons is in acetyl CoA?
2C
In the TCA cycle, acetyl CoA undergoes a reaction with what enzyme to make citrate? What vitamin is required here?
citrate synthase
vitamin required is vit B5
How many carbons is citrate?
6C
In the TCA cycle, citrate undergoes a reaction with what enzyme to make isocitrate?
aconitase
How many carbons is isocitrate?
6C
In the TCA cycle, isocitrate undergoes an oxidative decarboxylation reaction with what enzyme to make alpha KG? What else is made here?
isocitrate DH (IDH)
NADH was made and released along with CO2
How many carbons is alpha KG?
5C
In the TCA cycle, alpha KG undergoes an oxidative decarboxylation reaction with what enzyme to make succinyl-CoA, NADH, and CO2? What does this enzyme require?
alpha KG DH
requires TLCFN coenzymes
note: NADH and CO2 was released
How many carbons is succinyl-CoA?
4C
In the TCA cycle, succinyl-CoA undergoes substrate level phosphorylation with what enzyme to make GTP and succinate?
succinyl-CoA synthetase or succinate thiokinase
How many carbons is succinate?
4C
In the TCA cycle, succinate undergoes a reaction with what enzyme to make fumarate and FADH2?
succinate DH (SDH)
Where is SDH located?
in the inner mitochondrial membrane
SDH is a part of TCA and ETC
How many carbons is fumarate?
4C
In the TCA cycle, fumarate undergoes a hydration reaction with what enzyme to make malate?
fumarase
How many carbons is malate?
4C
In the TCA cycle, malate undergoes a reaction with what enzyme to make OAA and NADH?
malate DH
How many carbons is OAA?
4C
In the TCA cycle, do we create OAA?
no its recycled
What is the net yield from acetyl CoA?
-2 CO2
-3 NADH are used to make 9 ATP
-1 FADH2 is used to make 2 ATP
-1 GTP
=total ATP is 12 (this is ONE TURN)
at this point 1 acetyl CoA is completely oxidized
note: the net yield for a molecule of pyruvate will be one more NADH which will make 15 ATP in total
Glycolysis generates 6 or 8 ATPs and 2 pyruvates. So, the net gain from the aerobic catabolism of glucose will be ______ ATPs
36/38 (this is with oxygen present and vitamin B1 present)
note: G > pyr> lactate makes 2 ATP per G, this is without oxygen and vitamin B1
Is any carbon dioxide produced in glycolysis? Where is carbon dioxide produced?
no, glycolysis only makes 2 ATP and 2 NADH in the cytoplasm
pyr to acetyl CoA makes 2 CO2 and 2 NADH in the mitochondria
TCA cycle makes 4 CO2 and 24 ATP with 2 turns
Acetyl CoA has 2C so it can make…
2 CO2 and 12 ATP
pyruvate has 3C so it can make….
3 CO2 and 15 ATP
glucose has 6C so it can make….
6 CO2 and 36-38 ATP
When citrate levels are high, it wont go through TCA, instead it will convert to….
FAs and then fat or cholesterol
When alpha KG levels are high, it will not continue through TCA. Instead it will be converted to….
AAs, most commonly glutamate
or can convert to purines
When there are high levels of succinyl- CoA, it will not continue through TCA. Instead it will make….
heme
Can malate change to glucose?
yes
Where there are high levels of OAA, it can be converted to….
-AAs, most commonly aspartate
-glucose
-pyrimidines
T/F: the TCA cycle is an amphibolic pathway
true
When there are high levels of pyruvate, it can change to…
AAs or change back to glucose
What hormone removed phosphate to activate PDH?
insulin (so glucagon does the opposite)
this is covalent modification
What are the 5 allosteric activators for PDH?
increased:
-NAD+
-ADP
-CoA
-calcium
pyruvate
What are the 3 allosteric inhibitors of PDH?
increased:
-acetyl CoA
-NADH
-ATP
What is the major product of TCA cycle?
NADH because 3 NADH are created
How is the TCA cycle regulated?
ALLOSTERIC REGULATION ONLY
there is no hormone/covalent modification with TCA
T/F: the TCA cycle has NO diseases associated with it
true!!!
What are the 3 RLEs in TCA cycle?
1) citrate synthase
2) isocitrate DH (IDH)
3) alpha KG DH
What inhibits citrate synthase?
increased:
-NADH
-succinyl CoA
-citrate
-ATP
What inhibits IDH?
increased ATP and/or NADH
What inhibits alpha KG DH?
increased succinyl CoA and/or NADH
What activates citrate synthase?
increased ADP
What activates IDH?
increased ADP and/or calcium
What activates alpha KG DH?
increased calcium
What enzyme is the most regulated enzyme in TCA?
IDH
If a person keeps eating but TCA shuts down because of enough ATP, then the ATP will be used to make glycogen, and if theres still enough then it would activate….
PFK1
Is citrate a VIP molecule?
yes
When is the citrate shuttle used?
When TCA cycle slows down and theres still extra glucose to be used up
its used for anabolic pathways, specifically for converting citrate to FA or cholesterol
Where is the citrate shuttle located?
cytoplasm
What is the difference between malate and citrate shuttle in terms of fed/fasting state?
citrate shuttle is used in fed state
malate shuttle is used in fasted state
Citrate will get shuttled out of mitochondria when there is too much. It will break down into OAA and acetyl coa with which enzyme?
citrate lyase
Citrate will get shuttled out of mitochondria when there is too much. It will break down into OAA and acetyl CoA with citrate lyase. The acetyl CoA will be used to make malonyl CoA, whereas the OAA gets converted to malate. Malate is also a VIP molecule and can either be shuttled back into mitochondria and convert back to OAA to go through TCA when its needed, or malate can be converted to pyruvate with the help of what enzyme?
malic enzyme (this also makes NADPH)
Citrate will get shuttled out of mitochondria when there is too much. It will break down into OAA and acetyl CoA with citrate lyase. The acetyl CoA will be used to make malonyl CoA, whereas the OAA gets converted to malate. Malate is also a VIP molecule an can either be shuttled back into mitochondria and convert back to OAA to go through TCA when its needed, or malate can be converted to pyruvate with the help of malic enzyme (this also makes NADPH). Pyruvate is also a VIP and can be shuttled into mitochondria. Pyruvate can either convert to OAA or acetyl CoA depending on what is needed. What enzyme converts pyruvate to OAA?
pyruvate carboxylase
Anaplerotic reactions restock the TCA cycle, it usually involves the synthesis of _____________ to shuttle out of mitochondria in a fasting state
OAA or malate
Once malate moves out of the mitochondria, it never goes back because it will be used to make….
glucose (so after we’re fed, we have to restock TCA to make more malate)
In the liver and kidneys, pyruvate is converted to OAA with what enzyme?
pyruvate carboxylase
In the muscles, PEP is converted to OAA with what enzyme?
PEP CK
In all tissues, pyruvate is converted to malate with what enzyme?
malic enzyme
What enzymes are involved with pyruvate?
1) pyruvate kinase
2) pyruvate carboxylase
3) pyruvate DH
4) malic enzyme
5) lactate DH
6) PEPCK
Why can’t we make glucose from FAs but plants can?
because plants have glyoxylate shunt and we do not
Plants can make glucose from acetyl CoA since they have a mechanism that bypasses the reactions of the TCA cycle that causes CO2 to be lost
in plants, isocitrate gets broken down into glyoxylate and succinate with what enzyme?
isocitrate lyase
in plants, isocitrate gets broken down into glyoxylate and succinate with isocitrate lyase. The succinate will be transported out to eventually make OAA. But the glyoxylate will undergo a reaction with what enzyme to make malate?
malate synthase (this also makes CoA)
the new malate that was created can be converted to glucose
What enzymes do plants have that we do not?
isocitrate lyase and malate synthase
What 2 enzymes in the TCA cycle make NADH and CO2?
IDH and alpha KG DH
(malate DH makes NADH but not CO2)
What enzyme in TCA cycle can do substrate level phosphorylation?
succinyl CoA synthetase or succinate thiokinase
How many NADH are created per glucose?
10 NADH
2 in glycolysis
2 from PO
3 from TCA (6 with 2 rounds)
What enzymes make NADH in glycolysis?
GAP DH
What enzyme makes NADH in pyruvate oxidation?
PDH
How much ATP is made per glucose from glycolysis + TCA?
4 ATP
1 from phosphoglycerate kinase
1 from pyruvate kinase
2 GTP from succinate thiokinase (2 rounds)
How much FADH2 is made per glucose?
2 FADH2 (with 2 rounds of TCA with SDH)
What are the 5 VIP molecules we went over so far?
1) pyruvate
2) malate
3) citrate
4) aspartate
5) PEP
Midterm warning= she has a lot of vitamin questions on midterm so if you don’t know/remember them go back to very first deck and review!