Flashcards in TCA Cycle Deck (87):
What is so special about the TCA cycle?
Major energy producing pathway in the body
Where does the TCA cycle occur?
In what form does food product reach the TCA cycle?
What is the general idea of the CA cycle?
Take Acetyl CoA and oxidize it to make carbon dioxide and water in order to make energy.
Where are all of the enzymes we need for the TCA cycle?
All the enzymes of the TCA cycle are in the mitochondrial matrix except succinate dehydrogenase, which is in the inner mitochondrial matrix
Acetyl CoA and ozaloacetate condense to form what?
What enzyme condenses acetyl-CoA and oxaloacetate to make citrate?
Citrate is isomerized to what?
What enzyme turns citrate to isocitrate?
Isocitrate is oxidized to what?
What two step process is involved in turning isocitrate to alpha ketoglutarate?
(CO2 is produced and the electrons are passed to NAD+ to form NADH and H+)
What enzyme turns isocitrate to alpha ketoglutarate?
What activates isocitrate dehydrogenase? Inhibits it?
This key regulatory enzyme of the TCA cycle is allosterically activated by ADP and inhibited by NADH
What happens to alpha ketoglutarate once it is made?
converted to succinyl-CoA
Alpha ketoglutarate to Succinyl-CoA is an example of what kind of reaction?
oxidative decarboxylation reaction
What enzyme turns alpha-ketoglutarate to succinyl CoA?
What cofactors are required for α-ketoglutarate dehydrogenase?
This enzyme requires five cofactors: thiamine pyrophosphate, lipoic acid, CoASH, FAD, and NAD+
What happens to succinyl CoA?
cleaved to succinate
How do we get energy from the succinyl CoA to succinate reaction?
Cleavage of the high-energy thioester bond of succinyl-CoA provides energy for the substrate-level phosphorylation of GDP to GTP
What enzyme cleaves succinyl CoA to succinate?
succinate thiokinase aka succinyl-CoA synthetase
What happens to succinate?
oxidized to fumarate
What electron carrier is involved at the step where sucinate becomes fumarate?
succinate transfers two hydrogens together with their electrons to FAD, which forms FADH2
What enzyme oxidizes succinate to fumarate?
Where does the succinate to fumarate rxn occur?
Inner mitochondrial membrane
What happens to fumarate?
Converted to malate
What enzyme turns fumarate to malate?
How does fumarase turn fumarate to malate?
Adds water across the double bond
What happens to malate?
Oxidized to regenerate oxaloacetate
What oxidizes malate to oxaloacetate?
What enzyme carrier is involved with the malate dehydrogenase rxn?
two hydrogens along with their electrons are passed to NAD+, producing NADH and H+
How much ATP per NADH?
How much ATP per FADH2
How much ATP per turn of the TCA cycle?
1 mole of acetyl CoA gives us 10 moles of ATP
What happens during fasting?
Intermediates of the TCA cycle are utilized in the fasting state in the liver for the production of glucose and in the fed state for the synthesis of fatty acids
What are anaplerotic reactions?
Anaplerotic reactions replenish intermediates of the TCA cycle as they are removed for the synthesis of glucose, fatty acids, amino acids, or other compounds
One of the most important anaplerotic reactions?
Carboxylation of pyruvate to oxaloacetate
What enzyme carboxylates pyruvate to oxaloacetate?
What cofactor does pyruvate carboxylase need?
What activates the enzyme pyruvate carboxylase besides its cofactor biotin?
Where is pyruvate carboxylase found?
What reactions do amino acids do to produce TCA intermediates?
What amino acids form glutamate?
Glutamine, proline, arginine and histidine
What amino acid forms aspartate?
What becomes oxaloacetate?
Name of the reaction type that turns aspartate to oxaloacetate
How is Succinyl CoA formed?
Propionyl-CoA gets converted to methylmalonyl-CoA and subsequently to Succinyl-CoA
Formation of propionyl CoA
You need Valine, isoleucine, methionine and threonine
What amino acids make fumarate?
Phenylalanine, tyrosine, and aspartate
What pathway slows down the TCA cycle?
Gluconeogenesis, which uses intermediates of the TCAcycle
What happens to the TCA cycle as glucose is synthesized?
malate or oxaloacetate is removed from the TCA cycle and replenished by anaplerotic reactions
Pyruvate is formed by what compounds?
Lactate or alanine
What product of the TCA cycle is important for fatty acid synthesis?
What catalyzes the anaplerotic reactions that replenish the TCA cycle intermediates?
How can we get amino acids from glucose via the oxaloacetate pathway?
Glucose is converted to pyruvate, which forms oxaloacetate, which by transamination forms aspartate and, subsequently, asparagine
How can we get amino acids from glucose via the oxaloacetate and acetyl CoA pathway?
Glucose is converted to pyruvate, which forms both oxaloacetate and acetyl-CoA, which condense, forming citrate. Citrate forms isocitrate and then α-ketoglutarate, from which glutamate, glutamine, proline, and arginine are produced
What accelerates the ETC?
When ADP levels are high relative to ATP the reactions of the electron transport chain are accelerated.
What speeds up the TCA cycle?
NADH is rapidly oxidized by the ETC; consequently, the TCA cycle speeds up
What slows down the ETC?
When the concentration of ATP is high the electron transport chain slows down
What slows down the TCA cycle?
When the concentration of ATP is high the electron transport chain slows down, NADH builds up, and consequently the TCA cycle is inhibited
How, specifically, does the TCA cycle slow down (this is very involved, but think about the process)
NADH allosterically inhibits isocitrate dehydrogenase. Isocitrate accumulates, and because the aconitase equilibrium favors citrate, the concentration of citrate rises. Citrate inhibits citrate synthase, the first enzyme of the cycle.
What happens to oxaloacetate when NADH is high?
Oxaloacetate is converted to malate when NADH is high and, therefore, less substrate (OAA) is available for the citrate synthase reaction
What reactions are NAD used in?
isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, and malate dehydrogenase reactions
What is niacin important for?
Niacin is used for the synthesis of the nicotinamide portion of NAD
What is important for the production of FAD?
What is thiamine important for?
the synthesis of thiamine pyrophosphate
Importance of Pantothenate?
synthesis of CoASH
Effects of low Vitamin A
Night blindness and xerophthalmia
Effects of low Vitamin D
Inadequate bone mineralization, rickets in children
Effects of low Vitamin E
Reproductive failure, muscular dystrophy, neurologic abnormalities
Effects of low Vitamin K
Defective blood coagulation
Effects of low Vitamin C
Effects of low thiamine?
Effects of low riboflavin?
Oral-buccal cavity lesions
Effects of low niacin?
Pellagra (diarrhea, dermatitis, dementia, death)
Effects of low Vitamin B6
Convulsions, dermatitis, anemia
Effects of low Folate
Effects of low Vitamin B12?
Megaloblastic Anemia and neurological symptoms
Effects of low biotin
Anorexia, nausea, vomitis, glossitis, alopecia
Effects of low pantothenic acid
Listlessness, fatigue, burning feet syndrome
How do Carbons from glucose enter the TCA cycle?
In order for carbons from glucose to enter the TCA cycle, glucose is first converted to pyruvate by glycolysis, then pyruvate forms acetyl-CoA
How is acetyl CoA formed?
Pyruvate dehydrogenase catalyzes the oxidative decarboxylation of pyruvate, forming acetyl-CoA
Where is pyruvate dehydrogenase?
Pyruvate dehydrogenase, a multienzyme complex located exclusively in the mitochondrial matrix
What is similar between pyruvate dehydrogenase and alpha ketoglutarate?
They need the same 5 components
What is different between pyruvate dehydrogenase and alpha ketoglutarate?
In contrast to α-ketoglutarate dehydrogenase, a pyruvate dehydrogenase exists in a phosphorylated (inactive) form and a dephosphorylated (active) form
How is pyruvate decarboxylase deactivated?
CoASH and NAD+. Can also be inactivated by ADP
What activates the pyruvate decarboxylase?
The products of the pyruvate dehydrogenase reactions, acetyl-CoA and NADH. It is activated specifically by a phosphatase