Glycolysis & the TCA/Krebs Cycle

Question 1

What happens when mitochondrial fusion with ER tubules becomes more frequent than fission?

Answer 1

When fusion is more frequent, the mitochondria tend to become more elongated and interconnected, whereas a predominance of fission leads to the formation of more numerous and distinct mitochondria.

Question 2

What are cristae, and why are they important?

Answer 2

Cristae are a series of membranous sheets in the mitochondria. They contain a large amount of membrane surface, which houses the machinery needed for aerobic respiration and ATP formation.

Question 3

What is the composition of the mitochondrial matrix like?

Answer 3

The matrix has a gel-like consistency because of its high concentration (up to 500 mg/ml) of water-soluble proteins.

Question 4

Compare and contrast the structure of the inner and outer mitochondrial membranes.

Answer 4

The outer membrane is composed of approximately 50% lipid by weight and has a variety of enzymes. In contrast, the inner membrane contains over 100 different polypeptides and has a very high protein/lipid ratio. The inner membrane is devoid of cholesterol and rich in the phospholipid cardiolipin.

Question 5

What role does cardiolipin play?

Answer 5

Cardiolipin is important in facilitating the activity of several of the large protein complexes involved in electron transport and ATP synthesis.

Question 6

What are porins?

Answer 6

Porins are integral proteins that have a relatively large internal channel surrounded by a barrel of B strands.

Question 7

How does permeability differ between the inner and outer mitochondrial membranes?

Answer 7

When the porin channels are wide open, the outer membrane is freely permeable to ATP, NAD, and coenzyme A. In contrast, the inner mitochondrial membrane is highly impermeable; virtually all molecules and ions require special membrane transporters to gain entrance to the matrix.

Question 8

How do organisms such as yeast make NAD+?

Answer 8

Pyruvate is decarboxylated to acetaldehyde and carbon dioxide. Acetaldehyde is then reduced to ethanol, regenerating NAD+ in the process (and generating alcohol).

Question 9

What is the goal of fermentation (why is it necessary)?

Answer 9

The goal of fermentation is to allow the process of glycolysis to continue without oxygen. It oxidizes NADH in order to make NAD+ because for glycolysis to occur, the cell needs a constant supply of NAD+. Fermentation enables these conditions.

Question 10

Why is fermentation a sort of last-ditch process?

Answer 10

Fermentation is incredibly inefficient. More than 90% of energy in the glucose molecule is lost when a waste product such as lactic acid is made.

Question 11

What happens to the process of glycolysis if there is a shortage of NAD+?

Answer 11

When all of the NAD+ is reduced to NADH, glycolysis halts for lack of an electron acceptor, and ATP production ceases. To allow ATP production (for example, in a muscle during vigorous exercise), a short-cut reduces pyruvate to lactate, regenerating NAD+ for glycolysis.

Question 12

Why does the body have to use alternative sources of energy production during exercise?

Answer 12

Muscles in use increase ATP hydrolysis 100-fold over cells at rest. Therefore, the ATP stores for muscles are only available for 2-5 seconds of vigorous exercise. Because this is not long, the cells turn to sources such as creatine phosphate to supply the needed ATP.

Question 13

Distinguish between slow-twitch and fast-twitch muscle fibers.

Answer 13

Slow-twitch fibers aerobically produce ATP and work for a sustained period of activity. Fast-twitch fibers act with sudden force and produce ATP via anaerobic glycolysis. They work much faster, but with much more inefficiency as well.

Question 14

Describe the inefficiency of glycolysis.

Answer 14

Only about 2-3% of the energy stored in a molecule of glucose ends up in high-energy phosphate bond storage. There is a little more energy stored in NADH at the end, but that NADH is only accessible through oxygen in an aerobic environment. 90% of the energy lost is found in pyruvate.

Question 15

What are the three enzymes that can act upon pyruvate?

Answer 15

1. Pyruvate decarboxylase + alcohol dehydrogenase.
2. Lactate dehydrogenase
3. Pyruvate dehydrogenase

Question 16

In what conditions do the enzymes pyruvate decarboxylase + alcohol dehydrogenase act upon pyruvate?

Answer 16

In the absence of oxygen in a non-animal cell. It may happen during fermentation in yeast cells. This process produces ethanol as a toxic waste product.

Question 17

Under what condition does lactate dehydrogenase act upon pyruvate?

Answer 17

In the absence of oxygen in animal cells.

Question 18

Under what condition does pyruvate dehydrogenase act upon pyruvate?

Answer 18

In the presence of oxygen with mitochondrial function.

Question 19

How does the cell react when oxygen levels are high?

Answer 19

When oxygen levels are high, the hypoxia-inducible transcription factor (HIF-1a) is hydroxylated, associated with the VHL complex, and degraded by the proteasome.

Question 20

How does the cell react when oxygen levels are low?

Answer 20

When oxygen levels are low, HIF-1a translocates to the nucleus to bind to a sequence of DNA called the hypoxia response element. The genes of interest are “upstream” from genes that are controlled in this fashion, so by binding, the transcription of those genes will happen, leading to the proteins that need to be made.

Question 21

Besides ATP production, what other functions of the cell are the mitochondria involved in?

Answer 21

Apoptosis (a programmed form of cell death), necroptosis (a programmed inflammatory cell death), innate immunity, Ca2+ ion storage/homeostasis, and signaling.

Question 22

Because of their diverse functions, mitochondria are associated with a large number of heritable diseases. Name some of them.

Answer 22

Neuropathy, myopathy (defects of the muscle), exercise intolerance, diabetes, and deafness. These mitochondrial diseases affect about 1 in 8500 people.

Question 23

What is all the carbon dioxide we exhale a result of?

Answer 23

Carbon dioxide comes from the oxidation of pyruvate within the mitochondria.

Question 24

Every glucose molecule that enters the cell undergoes glycolysis. How do the fates of the resulting pyruvate molecules diverge after that?

Answer 24

The fate of a pyruvate molecule depends on the oxygen available. Without oxygen, pyruvate is reduced by NADH to lactate (and NAD+ forms). With oxygen, pyruvate is transported into the mitochondrion and completely oxidized during the TCA cycle; lots of NADH and ATP are formed.

Question 25

Describe the reaction that produces the first carbon dioxide molecule.

Answer 25

Pyruvate is acted upon by the pyruvate dehydrogenase enzyme and oxidized to an acetyl group attached to a carrier named coenzyme A. This oxidation is paired with the reduction of NAD+.

Question 26

What are the allosteric inhibitors of pyruvate dehydrogenase?

Answer 26

Acetyl-CoA and NADH are the allosteric inhibitors of the giant multienzyme complex that is pyruvate dehydrogenase.

Question 27

Define coenzyme.

Answer 27

Any molecule necessary for a reaction but not consumed by that reaction.

Question 28

What is the first step of the TCA cycle?

Answer 28

Condensation of acetyl group (2C) with oxaloacetate (4C) to form citric acid (6C).

Question 29

Name an allosteric inhibitor of the TCA cycle.

Answer 29

ATP feeds back to citric synthase as an allosteric inhibitor of the cycle.

Question 30

After the first step of the TCA cycle, what happens next?

Answer 30

Four redox reactions occur in which a pair of electrons are transferred from substrate to a coenzyme (these are reduction reaction tradeoffs for oxidizing carbon). 3 of the reactions reduce NAD+ to NADH. 1 reduces FAD to FADH2.

Question 31

Why would a reduction from FAD to FADH2 be more favorable than a reduction from NAD+ to NADH?

Answer 31

A FAD reduction captures some of the lower-energy reactions when the cell was low on energy to minimize energy loss.

Question 32

What are the products of one TCA cycle?

Answer 32

3 NADH, 1 FADH, 1 GTP, and 2 CO2.

Question 33

Describe the fatty acid B-oxidation cycle.

Answer 33

In this cycle, fatty acids are broken into acetyl-CoA. In the “investment” stage of the cycle, ATP is converted to AMP (counts as the expenditure of two ATP). A redox reaction occurs that converts FAD into FADH2.

Question 34

Explain the statement: “All catabolic pathways converge on the TCA cycle.”

Answer 34

The B-oxidation of fatty acids generates acetyl-CoA. Amino acid degradation does the same, as does glycolysis (the breakdown of carbohydrates). Essentially all foods are converted into acetyl-CoA and fed into the TCA cycle. If a molecule is too oxidized to break down into acetyl-CoA, they are fed into the TCA cycle at another point.

Question 35

Name the products per molecule of glucose up through the citric acid cycle.

Answer 35

4 ATP
10 NADH
2 FADH2
6 CO2