Lecture2-PYRUVATE METABOLISM&TCA CYCLE Flashcards
What is the primary role of mitochondria?
ATP production via aerobic respiration
Acetyl-coA is a common product in what?
catabolism of carbohydrates (glycolysis), amino acids and fatty acids (b-oxidation)
What type of pathway is the TCA cycle?
amphibolic pathway
What does it mean when the TCA cycle is amphibolic?
involving both catabolism (break down) and anabolism (synthesis) of molecules
What does it mean when the TCA cycle is amphibolic?
involving both catabolism (break down) and anabolism (synthesis) of molecules
What is the mitochondrial function?
-Tricarboxylic Acid Cycle
-beta-Oxidation of fatty acids
-Respiratory chain with ATP production through oxidative phosphorylation
What is the mitochondrial function?
-Tricarboxylic Acid Cycle
-beta-Oxidation of fatty acids
-Respiratory chain with ATP production through oxidative phosphorylation
what are the products of the TCA cycle?
NADH, FADH2 and GTP
What of the products of TCA cycle used for ?
used for ATP generation
what are the structures of the mitochondria?
outer membrane
inner membrane(cristae)
matrix
What is happening in the inner membrane (cristae)
oxidative phosphorylation
What is happening the matrix of the mitochondria?
PDH complex, TCA, Fatty acid B oxidation
Where is the PDH complex done?
matrix of the mitochondria
Where is the TCA cycle done?
Matrix of the mitochondria
Where does oxidative phosphorylation done?
Inner membrane of mitochondria
What are the metabolic fates of pyruvate?
Alanine (transmutation), oxaloacetate (Carboxylation), aceyl CoA(Oxidative decarboxylation) and Lactate (reduction)
Tell me about the pyruvate transport
A variety of different transport systems, such as symports and antiports, are present in the inner mitochondrial membrane
- pyruvate transport has a pyruvate symport or shuttle that diffuses pyruvate(-) and H(+) through the inner mitochronial membrane . Since they are opposite charges they do not affect the electron gradient
What does the Pyruvate dehydrogenase complex do?
oxidative decarboxylation of pyruvate
What is the first step of the PDH complex?
Pyruvate to hydroxyethyl with pyruvate dehydrogenase
What allows the lipoid acid prosthetic group to rotate?
Lipoid acid is joined by an amide link to a lysine residue of the transacetylase component of the enzyme complex
What is the product of the Dihydrolipidyl transacetylase
Acetyle CoA
What is the product of the dihydrolipoyl dehydrogenase
NADH and H+
What are the products of the PDH complex?
NADH and H+
Acetyl CoA
How do you deactivate the PDH complex?
Active PDH Kinase through phosphorylation of PDH
(high ATP, high acetyl coA)
How can you decrease the activity of pyruvate dehydrogenase (PDH) kinase?
Low ATP, Low acetyl CoA
How you can increase the activity of pyruvate dehydrogenase (PDH) kinase) ?
HIGH ATP, HIGH acetyl Co-A
How do you active the PDH Complex
dephosphrolation of PDH with pyruvate dehydrogenase phosphatase
How do you increase the activity of pyruvate dehydrogenase phosphatase
Increase Mg, Insulin
What are the sources of Acetyl CoA
Pyruvate, amino acids, fatty acids
What are the fates of acetyl CoA
Tricarboxylic acid cycle, ketone bodies, sterols and fatty acids
What are the fates of acetyl CoA
Tricarboxylic acid cycle, ketone bodies, sterols and fatty acids
what are high energy molecules in the TCA cycle
acetyl coA, and succinyl CoA
What three enzymes involve a lot of energy, exergonic?
Citrate synthase, isocitrate dehydrogenase and alpha ketaoglutarate dehydrogenase
What is the rate limiting enzyme in TCA cyle
Isocitrate dehydrogenase
-isocitrate to a ketoglutaurate
What is the first oxidation step in TCA cycle
NADH, H–> Isocitrate to oxalosuccinate with isocitrate dehydrogenase
Extra under oxalosuccinate: electron sink beta to carbon with COO to be removed
What is the second oxidation in TCA?
NADH, H –> a-ketoglutrate aKG to succinyl CoA with a ketoglutarate dehydrogenase
C is converted to COs2
What is the high energy molecule formed in TCA and what step?
GTP and succinyl CoA to succinate with succinyl CoA synthetase
what is the 3rd oxidation in TCA
FAHH2 –>Succinate to fumarate with succinate dehydrogenase
What the final oxidation in TCA?
NADH+H –> L-malate to oxaloacetate with malt dehydrogenase
Where do you regulate the TCA cycle?
The 3 TCA cycle exergonic steps:
-Citrate synthase
-Isocitrate dehydrogenase (catalyzes rate-limiting step)
-a-Ketoglutarate dehydrogenase
Where do you regulate the TCA cycle?
The 3 TCA cycle exergonic steps:
-Citrate synthase
-Isocitrate dehydrogenase (catalyzes rate-limiting step)
-a-Ketoglutarate dehydrogenase
What inhibits the TCA cycle?
ATP, NADH, succinyl-CoA
TCA is activated by what?
ADP and Ca++
ADP and CA+ does what to the TCA cycle?
activate it
What does ATP, NADH and succinyl-coA do to the TCA cycle?
inhibit it
The pyruvate dehydrogenase complex is controlled by what?
allosteric and covalent mechanisms
Oxaloactate from the TCA cycle goes where?
Amino acid synthesis
Malate from the TCA cycle goes where?
gluconeogenesis
succinyl coA from the TCA cycle goes where?
heme synthesis
alpha ketoglutarate from the TCA cycle goes where?
Amino acid synthesis
Citrate from the TCA cycle goes where?
fatty acid synthesis
There is a metabolic problem with the TCA cycle, what is it?
to run TCA cycle you need not only acetyl-CoA but also oxaloacetate
What is the solution of the metabolic problem of the TCA cycle?
Pyruvate carboxylase (+biotin) converts pyruvate to oxaloacetate
What from the TCA can be toxic?
accumulation of the TCA cycle intermediates (succinate, fumarate) or TCA cycle substrates (pyruvate)
an accumulation of TCA cycle intermediates (succinate, fumarate) or TCA cycle substrates (pyruvate) cause what?
particularly toxic to neurons and brain development (encephalopathies)
What is Pyruvate dehydrogenase deficiency ?
-leading to chronic lactic acidosis (increased serum levels for lactate, pyruvate, alanine).
-Children with this disease frequently exhibit severe neurological defects; resulting in death in many cases
- Dietary management may include ketogenic diet
What is the management of pyruvate dehydrogenase deficiency?
ketogenic diet (high-fat, adequate- protein, low-carbohydrate diet) with minimal carbohydrates.
What is fumarase deficiency?
-Rare autosomal recessive disease with severe neurological impairment.
-Urine contains abnormal amounts of fumarate and elevated levels of succinate and other TCA cycle intermediates.
