TCA/link reaction (pyruvate -> Acetyl CoA)

Explain what happens briefly in the Citric Acid Cycle. 

• Addition of Acetyl-coA to a 4C organic acid to form a 6C organic acid

• 6C -> 5C -> 4C, then the 4C compound is converted back to original 4C acid

• Involves removal of hydrogens to generate reduced coenzyme

• addition of OH and H groups by hydration of double bonds and decarboxylation

• 1 GTP is produced

none of the oxidation reactions in the TCA involve

molecular oxygen

in the TCA there is a net addition of oxygen, added as -

OH in water

the citric acid cycle occurs in the - of eukaryotes and is associated with the - in bacteria

mitochondria, cytoplasmic membrane

pyruvate is a product of - and can be converted to acetyl-CoA via -

glycolysis, oxidative decarboxylation

decarboxylation is -

irreversible

one glucose can produce - acetyl CoA molecules

two

three important sources of acetyl-CoA

1. decarboxylation of pyruvate from CHO, fatty acids, amino acids

2. breakdown of fatty acids

3. breakdown of leucine

the TCA cycle can metabolize the carbon skeletons of amino acids that are NOT broken down to acetyl-CoA by being converting them into - such as - (five things)

intermediates of the TCA cycle; pyruvate, α-ketoglutarate, succinyl-CoA, fumarate, or oxaloacetate

structure of oxaloacetate

structure of citrate

structure of isocitrate

structure of α-ketoglutarate

structure of cis-aconitate

structure of succinyl CoA

structure of succinate

structure of fumarate

structure of malate

order of acids in the TCA cycle

1. oxaloacetate

2. citrate

3. cis-aconitate

4. isocitrate

5. α-ketoglutarate

6. succinyl-CoA

7. succinate

8. fumarate

9. malate

oxaloacetate → citrate enzyme?

citrate synthase

citrate → cis-aconitate → isocitrate enzyme?

aconitase

isocitrate → α-ketoglutarate emzyme?

isocitrate dehydrogenase

α-ketoglutarate → succinyl CoA

α-ketoglutarate dehydrogenase complex

succinyl CoA → succinate enzyme?

succinyl CoA synthetase

succinate → fumarate enzyme?

succinate dehydrogenase

fumarate → malate enzyme?

fumarase

malate → oxaloacetate enzyme?

malase dehydrogenase

in the TCA cycle, which substrates are 6C?

citrate, cis-aconitate, isocitrate

in the cycle, which substrate is 5C?

alpha-ketogluterate

in the TCA cycle, which substrates are 4C?

succinyl-CoA, succinate, fumarate, malate, oxaloacetate

Which steps in the TCA cycle is there a loss of CO2?

1. isocitrate → alpha-ketogluterate

2. alpha-ketogluterate → succinyl-CoA

citrate synthase catalyzes the - of acetyl-CoA and oxaloacetate to form -. This reaction is - and highly exergonic

condensation, citrate, irreversible

aconitase converts citrate into - through a two-step reaction involving the intermediate -. This reaction facilitates the rearrangement of the - group for subsequent -

isocitrate, cis-aconitate, hydroxyl, oxidation

isocitrate dehydrogenase catalyzes the - and - of isocitrate to form -. This reaction also produces - and releases -

oxidation, decarboxylation, α-ketoglutarate, NADH, CO2

α-ketoglutarate dehydrogenase catalyzes the - of α-ketoglutarate to form -. This step generates - and releases -

oxidative decarboxylation, succinyl-CoA, NADH, CO2

succinyl-CoA synthetase converts succinyl-CoA into -, coupled with the production of -. This is the only - step in the cycle

succinate, GTP, substrate-level phosphorylation

succinate dehydrogenase catalyzes the - of succinate to -, producing -

oxidation, fumarate, FADH2

fumarase hydrates fumarate to form -

malate

malate dehydrogenase catalyzes the - of malate to regenerate -, producing - in the process

oxidation, oxaloacetate, NADH

in aerobic organisms the citric acid cycle can only function in aerobic tissue because the - must be regenerated by the -

reduced coenzymes, ETC

which steps in the TCA cycle are NADH and FADH2 formed?

isocitrate dehydrogenase, succinate dehydrogenase, malase dehydrogenase

which step in the TCA cycle is GTP formed?

succinyl synthetase

BeriBeri?

a disease caused by - deficiency and it was a serious health problem in the far east because - has a low content of -

thiamine, white rice, thiamine

thiamine pyrophosphate TPP is a prosthetic group of 3 important enzymes

1. pyruvate dehydrogenase

2. α-ketoglutarate dehydrogenase complex

3. transketolase

the function of lipoamide prosthetic group

hold pool of acetyl groups and transfers between enzyme subunits in pyruvate dehydrogenase complex

what are some biosynthetic precursors which are derived from the citric acid intermediates? (remember at least three)

1. citrate → fatty acids, sterols

2. alpha-ketogluterate → glutamate → other AA, purines

3. succinyl CoA → heme, chlorophyll

4. malate → pyruvate

5. oxaloacetate → PEP, aspartate →other AA, purines, pyrmidines

two AA and the citric acid intermediates from which they are immediately derived from

alpha-ketogluterate → glutamate

oxaloacetate → aspartate

- can be fed into the citric acid cycle to form cycle intermedaites

carbon chains of amino acids

what happens in glyoxylate cycle?

• allows production of glucose from acetyl-CoA

• bypasses the decarboxylation steps in citric acid cycle

• involves addition of a second acetyl CoA

• the net affect is the production of a new 4C succinate with each turn of the cycle

What are the two enzymes that form the bypass between isocitrate and malate. 

1. malate synthase

2. isocitrate lyase

briefly describe the reaction used to form acetyl-CoA from acetate

• synthesize AcCoA from acetate and CoA by an ATP-dependent reaction using acetyl CoA synthetase aka AMP

the main fate of succinate produced by glyoxylate cycle?

ultimately becomes oxaloacetate used for gluconeogenesis and other uses

Briefly describe the role of isocitrate as the branch point between the citric acid cycle and the glyoxylate cycle (what are the two possible reactions)

1. isocitrate dehydrogenase of TCA→ α-ketoglutarate

2. isocitrate lyase of glyoxylate cycle→ succinate and glyoxylate

availability of isocitrate and the competing enzymes determine which way the pathway will proceed

The - level influences the choice between the pathways

if energy is low, isocitrate → -

if energy is high, isocitrate → - → -

ATP/ADP

alpha-ketogluterate

glyoxylate + succinate, gluconeogenesis

citric acid cycle is regulated to provide the correct balance between - needs and - needs

energy, precursor

the enzyme that is regulated to control the amount of acetyl-CoA produced from pyruvate is

pyruvate dehydrogenase complex

inhibition of pyruvate dehydrogenase complex by - inactivates PDH complex

PDKinase phosphorylation

PDH complex becomes inactive when a specific - residue of pyruvate dehydrogenase is -

serine, phosphorylated

high ratios of (three) can enhance phosphorylation of a specific serine residue, resulting in - of PDH complex

acetyl CoA/CoA, NADH/NAD+, and ATP/ADP; inactivation

phosphorylation of specific serine residue on PDH complex is inhibited by - or -

pyruvate, analogues

PDH complex becomes active again when a specific - hydrolyzes the P

dephosphorylation is enhanced by an increase in - and -

phosphatase

Ca++, insulin

the three main enzymes that are regulated to control the rate of citric acid cycle?

1. citrate synthase

2. isocitrate dehydrogenase

3. alpha-ketogluterate dehydrogenase

- is an inhibitor of citrate synthase

ATP

(three) are mutually cooperative stimulators of isocitrate dehydrogenase

NAD+, Mg++, and ADP

(two) are inhibitors of isocitrate dehydrogenase

ATP and NADH

(three) are inhibitors of alpha-ketogluterate dehydrogenase

succinyl CoA, NADH, and high energy charge

it is possible for the two sides of the TCA cycle to run in opposite directions by

???

the rate of citrate synthase can be regulated with concentration of (two)

high levels of - will promote citrate synthase activity

high levels of - will inhibit citrate synthase activity

substrate and product

oxaloacetate

citrate

any - reaction will overcome the regulation of citrate synthase as they will increase supply of -

anaplerotic, TCA cycle intermediates

it is logical for the TCA cycle to be inhibited by ATP because when ATP levels are -, there is no need for continued -

high, ATP production