Flashcards in TCA eBook Deck (30):
Starting product for the TCA cycle
Acetyl CoA (made after aerobic glycolysis end - which produces pyruvate and then a linker reaction converted pyruvate to acetyl CoA)
Under conditions of immediate need for ATP, what is the destiny of acetyl CoA?
Acetyl CoA formation ....
an irreversible reaction
Function of acetyl CoA
(1) connection between glycolysis and the TCA cycle
(2) substrate for fatty acid and cholesterol biosynthesis
Describe process of pyruvate to acetyl CoA
Pyruvate in the cytoplasm is transported into the mitochondria and is converted to the two-carbon acetyl CoA by the pyruvate dehydrogenase complex in an irreversible reaction that produces NADH and release the first free CO2
Describe pyruvate dehydrogenase complex
Three enzymatic activites - a decarboxylase, transacetylase, and a dehydrogenase. It employs 5 co-fasters - thiamine pyrophosphate, FAD, NAD, CoA and lipoic acid
After conversion of pyruvate to acetyl CoA, s acetyl CoA destined for TCA cycle?
While the pyruvate → acetyl CoA step does not commit acetyl CoA to the TCA cycle, it does decide the fate of pyruvate.
Negative regulation of pyruvate dehydrogenase?
acetyl CoA and high levels of NADH; ATP, acetyl CoA and NADH collaborate on inhibtion of pyruvate dehydrogenase by a second method as well - stimulates phorphorylation of dehydrogenase which inhibits it (covalent inhibition of pruvate dehydrogenase omplex)
What prevents the phosphorylation of pyruvate dehydrogenase (prevent its inactivation)?
High concentrations of CoA, NAD+, or pyruvate; inhibit this kinase, allowing a competing phosphatase to reactive the dehydrogenase
When does the TCA cycle begin?
Begins with the conversion of acetyl CoA and oxaloacetate to citrate and free CoA
What does citrate synthase do?
Citrate synthase is the initial enzyme of the. tricarboxylic acid (TCA) cycle. The enzyme catalyzes. the reaction between acetyl coenzyme A (acetyl CoA) and oxaloacetic acid to form citric acid.
What else can acetyl CoA be used for?
Fatty acid or cholesterol synthesis
Allosteric inhibition of Citrate sythase?
ATP, NADH, succinyl CoA
Fate of citrate?
Citrate is then isomerized to isocitrate by the enzyme aconitase in a reversible reaction.
Fate of isocitrate?
Isocitrate dehydrogenase converts isocitrate to α-ketoglutarate, with the production of one CO2 and the reduction of NAD to NADH.
Fate of α-ketoglutarate?
α-ketoglutarate is then converted into succinyl
CoA by the α-ketoglutarate dehydrogenase complex.
Co-factor requirement for α-ketoglutarate dehydrogenase complex?
Substrate level phosphorylation
The conversion of succinyl CoA to succinate is the site for another substrate level hosphorylation, this time with the production of GTP (which can later be used to convert ADP to
ATP via the enzyme nucleotide diphosphate kinase).
What are the three enzymes that regulate flux through the TCA cycle?
Citrate synthase, isocitrate dehydrogenase, and alpha-ketoglutaratedehydrogenase
Principal players "recycling" NAD and FAD?
O2, Pi and the ratio of ADP (and Pi) to ATP
Effects of high concentrations of citrate?
will shut down glycolysis; instead, metabolize fatty acids via beta-oxidation (the cleavange of fatty acids into acetyl CoA) ; conserve glucose for brain
Effects of high concentrations of citrate in the liver?
In liver, citrate is unable to shut down glycolysis since it allosteric activation of PFK-1 by fructose-2,6 bisphosphate when insulin is signaling is much stronger than the allosteric inhibition by citrate.
This allows liver to store excess glucose as fatty acids to be used under fast state.
One mechanism for pyruvate dehydrogenase complex deficiency
X-linked mutation of the E1 subunit of the PDC. Normally, thiamin binds to the E1 subunit of PDC. In this mutation, thiamin affinity to the enzyme is reduced.
Sign/symptoms of pyruvate dehydrogenase complex deficiency?
Lactic acidosis (pyruvate shunted to lactate), neurological syptoms (hypotonai, seizures, lethargy, mental deficiencies, etc.) from decreased energy
Treatment for pyruvate dehydrogenase complex deficiency?
most treatments are not successful.
(1) Thiamine supplementation
(2) ketogenic diet - alternative to glucose for energy for brain
Why is arsenic so dangerous?
Arseni interferes with the E2 subunit of dehydrogenase enzymes resulting in a clnical picture similar to PDC deficiency with patients showing signs of lactic acidosis and neurological impairent.
Classical indication of arenic poisoning?
Garlic-scented breath from oxidized arsenic
Consequences of a vitamin B1 deficiency?
Vit. B1 - essential for dehydrogenase enzymes (PDC, alpha-ketoglutarate dehydrogenase complex and branched-chain alpha keto acid dehydrogenase) ; deficiency leads to impaired carbohydrate, lipid and amino acid metabolism. B1 deficiency is typically seen in alcoholic
Signs and symptoms of a vitamin B1 deficiency
Wet beriberi and dry beriberi