The Mitochondria And Pdc Metabolism

Front 1

How can you determine the protonated form of a compound in given conditions?

Back 1

By comparing the pK of each acidic/basic groups with the pH of the medium.

Front 2

What characteristic structures of the mitochondria suggests its bacterial ancestry? (2)

Back 2

1: It has an inner and outer membrane

2: It has a circular DNA

Front 3

How many polypeptides are coded in the mitochondrial genome and what is how many are devoted to the electron transport chain

Back 3

13 polypeptides comes from the mitochondria and 11 are for the electron transport chain.

Front 4

Why most of the mitochondrial proteins are coded in the nucleus and synthesized in the cytoplasm and transported in the mitochondria?

Back 4

The mitochondria is the main producer of oxygen reactive species which highly damages DNA. Minimizing DNA content in the mitochondria will minimize alteration risks.

Front 5

How many types of Tim are in the mitochondria and what are their purpose?

Back 5

2 types: one to produce free floating proteins while the other is for inter membrane proteins?

Front 6

What compound inhibits mitochondrial protein synthesis and what is its mechanism?

Back 6

Chloramphenicol. It inhibits peptidyl transferase reactions in protein synthesis.

Front 7

What is the general given name for the mitochondrial outer membrane channel that allows protein transport in the mitochondria.

Back 7

It is usually referred as Tom. (Tom 40,70,20,22)

Front 8

What are three example of sources of acetyl coA?

Back 8

1: Pyruvate

2: Fatty acid

3: amino acid

Front 9

What is the primary function of the pyruvate dehydrogenase complex ?

Back 9

It catalyses the decarboxylation of pyruvate into acetyl coA.

Front 10

Where does pyruvate have to go to get affected by the pyruvate dehydrogenase complex and what transporter brings it there? What type of transporter is it ?

Back 10

It has to go to the mitochondria. the pyruvate translocase will bring it inside the mitochondria. It is a H+ symport.

Front 11

How does a symport work?

Back 11

It couples the transport of a molecule down its concentration gradient (exergonic) with a molecule up its concentration gradient (endergonic). This allows the unfavorable transport to happen.

Front 12

How is ADP and ATP transported in and out of the mitochondria?

Back 12

With the ADP/ATP antiport

Front 13

What is the proton gradient in the mitochondria ( inter membrane space vs inner space) and by what is it maintained?

Back 13

[H+] inter membrane space >> [H+] inner space.

This is maintained by the electron transport chain.

Front 14

What is the name of the most important proton transporter in the mitochondria?

Back 14

ATP synthase.

Front 15

What is the name of the E1 subunit of the Pyruvate dehydrogenase complex?

Back 15

Pyruvate dehydrogenase.

Front 16

What is the name of the E2 subunit of the Pyruvate dehydrogenase complex?

Back 16

Dihydrolipoyl transacetylase

Front 17

What is the name of the E3 subunit of the Pyruvate dehydrogenase complex?

Back 17

Dihydrolipoyl dehydrogenase.

Front 18

What are the two additional enzymes that control the Pyruvate dehydrogenase complex's activity?

Back 18

There is pyruvate dehydrogenase kinase and pyruvate dehydrogenase phosphotase.

Front 19

What are the four vitamins essential for the Pyruvate dehydrogenase complex?

Back 19

1: Thiamine

2: Panthotenic Acid

3: Riboflavin

4: Niacin

Front 20

What vitamin give rise to the cofactor coenzyme A?

Back 20

Panthotenic Acid.

Front 21

What can a deficiency in thiamine cause ?

Back 21

Beriberi syndrom ( loss of neural function).

Front 22

What system in the body is especially dependent on the Pyruvate dehydrogenase complex and for what reason?

Back 22

The central nervous system as brain tissue do not have reserves of glycogen ( poor at anaerobic respiration).

Front 23

What two organs consumes the biggest amount of glucose?

Back 23

The heart and the brain.

Front 24

What is the overall reaction mediated by the pyruvate dehydrogenase complex?

Back 24

pyruvate + CoA + NAD+ ---> Acetyl CoA + CO2 + NADH

Front 25

What are the advantages (3) of multienzyme complexes such as the pyruvate dehydrogenase complex?

Back 25

1: Coordinate control of the enzyme (inhibiting one enzyme will inhibit the complex)

2: Substrates travel distance is minimized between the enzymes.

3: Intermediates are channeled between successive sites. (related to above)

Front 26

how does the first enzymatic reaction of the Pyruvate dehydrogenase complex occur?

Back 26

Nucleophilic attack by TPP (from thiamine) on the carbonyl group of pyruvate which leads to removal of CO2 and a remaining 2 carbon molecule attached to TPP. this catalyzed by pyruvate dehydrogenase.

Front 27

What type of reaction occurs in E1? (2)

Back 27

1: Covalant catalysis

2: decarboxylation

Front 28

Why is the first enzymatic reaction of the Pyruvate dehydrogenase complex irreversible?

Back 28

Because the released CO2 as a gas escapes which renders the revers reaction impossible.

Front 29

What is the important component of dehydrolipoyl transacetylase in the second reaction of the Pyruvate dehydrogenase complex?

Back 29

The lipoamide arm.

Front 30

What happens in the second reaction of the Pyruvate dehydrogenase complex?

Back 30

The hydroxyethyl group ( from pyruvate) is reduced to acetic acid and esterified by one of the lipoamide SH groups and creates a thioester bond.

Front 31

What is the name of the group between the lipoamide disulfide bond and the E2 polypetide backbone?

Back 31

The liposyllysyl arm.

Front 32

What happens in the third reaction of the Pyruvate dehydrogenase complex?

Back 32

The thioester bond is broken in order to transfer the acyl group ( from pyruvate) to CoA which yields acetyl-CoA.

Front 33

What are the 3 chemical transformation of pyruvate in the Pyruvate dehydrogenase complex?

Back 33

1: Decarboxylation

2: Oxidation of keto group to carboxyl (C2)

3: linkage through Thioester bond with CoA

Front 34

What type of reaction allows the regeneration of lipoamide in E2 by reacting with E3?

Back 34

A disulfide exchange reaction.

Front 35

How is lipoamide regenerated in E2?

Back 35

It reacts with the FAD of E3 which transfer the S-S bond back to E2 ( FAD has a S-S bond). FAD is inturn oxidize by NAD+ forming two NADHs and returning FAD to the S-S form.

Front 36

What two enzymes does Arsenic affect ?

Back 36

The Pyruvate dehydrogenase complex and the alphe-ketogluterate dehydrogenase.

Front 37

Where does Arsenite toxicity come from? ( explain the mechanism)

Back 37

Arsenite can form a bidentate adduct with the disulfide group of lipoamide, effectively blocking its action in the Pyruvate dehydrogenase complex and the alphe-ketogluterate dehydrogenase.

Front 38

Why is Arsenate so toxic in metabolism?

Back 38

It has an analogus structure to PO4-3, hence it competes in any reactions that involve phosphate.

Front 39

What enzyme is most affected by arsenate?

Back 39

Glyceraldehyde-3-phosphate dehydrogenase.

Front 40

What is the net energetic result of glycolysis when poisoned by arsenate (typically)

Back 40

There is no net production of ATP ( or minimal). You use 2 ATP in the reaction but Arsenate will stop the reaction chain at glyceraldehyde-3-phosphate dehydrogenase step which only allows the production of 1 NADH molecule that can lead to a production of either 3 or 2 ATP. Hence, it is non-productive.

Front 41

Channeling of the metabolic intermediates of an enzymatic complex give rise to two advantages: what are they?

Back 41

1: Side reactions are minimized

2: Protects unstable intermediates ( hence more efficient)

Front 42

What are the two main enzymes mediating the control of pyruvate metabolism ?

Back 42

Pyruvate dehydrogenase complex and lactate dehydrogenase.

Front 43

In a nut shell, what is the Warburg effect?

Back 43

Effect where cancer cells inactivate the pyruvate dehydrogenase complex through phosphorylation and forces the conversion of pyruvate to lactate ( anaerobic respiration).

Front 44

What are the two levels of control for pyruvate dehydrogenase complex?

Back 44

1: Product inhibition ( allosteric inhibition)

2: Covalent modification ( phosphorylation)

Front 45

What are the two products of the pyruvate dehydrogenase complex that inhibits it? How do these products inhibit the complex?

Back 45

Acetyl-CoA and NADH. In excess, they will drive E3 backwards, reducing both Lipoamide and FAD, preventing further enzymatic activity by these sub-units.

Front 46

Why is it crucial to have a high regulation of the pyruvate dehydrogenase complex?

Back 46

Because the reaction is irreversible and the eukaryotic cell cannot synthesize glucose from acetyl-CoA ( There is no turning back from this point on in the metabolic pathway).

Front 47

What allosterically activate pyruvate dehydrogenase kinase?

Back 47

NADH and Acetyl-CoA.

Front 48

What is the targeted sub-unit of the pyruvate dehydrogenase kinase?

Back 48

pyruvate dehydrogenase or E1.

Front 49

What is the consequence of a high energy charge on the pyruvate dehydrogenase complex?

Back 49

High energy charge induces allosteric and covalent inhibition of the complex.

Front 50

You find a cell that has a high concentration of m-pyruvate dehydrogenase. What are the most probable concentrations (high or low) of NADH, Acetyl-CoA ? In these circumstances, what would Acetyl-CoA be most likely used for?

Back 50

[NADH] and [Acetyl-CoA] must be very high since pyruvate dehydrogenase is phosphorylated. This means that the cell no longer requires large amounts of energy. Acetyl-CoA could be used for synthesizing fatty acids.

Front 51

What factors activates pyruvate dehydrogenase phosphatase? Give an example of a source for an increase in concentration in any of these factors.

Back 51

The enzyme is activated by Ca2+ and Md2+. An instance where you could see drastic changes in [Ca2+] is in muscle contraction.

Front 52

What factors (5) inhibit pyruvate dehydrogenase kinase?

Back 52

Ca2+, Mg2+, pyruvate, ADP and k+.

Hint 52

3 ions and 2 organic molecules