TCA eBook

Question 1

Starting product for the TCA cycle

Answer 1

Acetyl CoA (made after aerobic glycolysis end - which produces pyruvate and then a linker reaction converted pyruvate to acetyl CoA)

Question 2

Under conditions of immediate need for ATP, what is the destiny of acetyl CoA?

Answer 2

TCA cycle

Question 3

Acetyl CoA formation ….

Answer 3

an irreversible reaction

Question 4

Function of acetyl CoA

Answer 4

(1) connection between glycolysis and the TCA cycle

(2) substrate for fatty acid and cholesterol biosynthesis

Question 5

Describe process of pyruvate to acetyl CoA

Answer 5

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

Question 6

Describe pyruvate dehydrogenase complex

Answer 6

Three enzymatic activites - a decarboxylase, transacetylase, and a dehydrogenase. It employs 5 co-fasters - thiamine pyrophosphate, FAD, NAD, CoA and lipoic acid

Question 7

After conversion of pyruvate to acetyl CoA, s acetyl CoA destined for TCA cycle?

Answer 7

While the pyruvate → acetyl CoA step does not commit acetyl CoA to the TCA cycle, it does decide the fate of pyruvate.

Question 8

Negative regulation of pyruvate dehydrogenase?

Answer 8

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)

Question 9

What prevents the phosphorylation of pyruvate dehydrogenase (prevent its inactivation)?

Answer 9

High concentrations of CoA, NAD+, or pyruvate; inhibit this kinase, allowing a competing phosphatase to reactive the dehydrogenase

Question 10

When does the TCA cycle begin?

Answer 10

Begins with the conversion of acetyl CoA and oxaloacetate to citrate and free CoA

Question 11

What does citrate synthase do?

Answer 11

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.

Question 12

What else can acetyl CoA be used for?

Answer 12

Fatty acid or cholesterol synthesis

Question 13

Allosteric inhibition of Citrate sythase?

Answer 13

ATP, NADH, succinyl CoA

Question 14

Fate of citrate?

Answer 14

Citrate is then isomerized to isocitrate by the enzyme aconitase in a reversible reaction.

Question 15

Fate of isocitrate?

Answer 15

Isocitrate dehydrogenase converts isocitrate to α-ketoglutarate, with the production of one CO2 and the reduction of NAD to NADH.

Question 16

Fate of α-ketoglutarate?

Answer 16

α-ketoglutarate is then converted into succinyl

CoA by the α-ketoglutarate dehydrogenase complex.

Question 17

Co-factor requirement for α-ketoglutarate dehydrogenase complex?

Answer 17

CoA, NAD

Question 18

Substrate level phosphorylation

Answer 18

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).

Question 19

What are the three enzymes that regulate flux through the TCA cycle?

Answer 19

Citrate synthase, isocitrate dehydrogenase, and alpha-ketoglutaratedehydrogenase

Question 20

Principal players “recycling” NAD and FAD?

Answer 20

O2, Pi and the ratio of ADP (and Pi) to ATP

Question 21

Effects of high concentrations of citrate?

Answer 21

will shut down glycolysis; instead, metabolize fatty acids via beta-oxidation (the cleavange of fatty acids into acetyl CoA) ; conserve glucose for brain

Question 22

Effects of high concentrations of citrate in the liver?

Answer 22

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.

Question 23

One mechanism for pyruvate dehydrogenase complex deficiency

Answer 23

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.

Question 24

Sign/symptoms of pyruvate dehydrogenase complex deficiency?

Answer 24

Lactic acidosis (pyruvate shunted to lactate), neurological syptoms (hypotonai, seizures, lethargy, mental deficiencies, etc.) from decreased energy

Question 25

Treatment for pyruvate dehydrogenase complex deficiency?

Answer 25

most treatments are not successful.
Options:
(1) Thiamine supplementation
(2) ketogenic diet - alternative to glucose for energy for brain

Question 26

Why is arsenic so dangerous?

Answer 26

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.

Question 27

Classical indication of arenic poisoning?

Answer 27

Garlic-scented breath from oxidized arsenic

Question 28

Consequences of a vitamin B1 deficiency?

Answer 28

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

Question 29

Signs and symptoms of a vitamin B1 deficiency

Answer 29

Wet beriberi and dry beriberi

Question 30

Treatment of a vitamin B1 deficiency?

Answer 30

correction of underlying deficiency