The acetyl CoA formed from ethanol then enters the TCA cycle and is oxidized to

Question

The acetyl CoA formed from ethanol then enters the TCA cycle and is oxidized to CO2 and water as normal. Given this pathway and the pathways you know, please answer the following:

a. How many electrons pass through the mitochondrial electron transport chain per ethanol molecule oxidized?

b. How many protons are pumped in the process? Remember that not all electrons go through NADH, some enter the electron transfer chain via FADH2 in Complex II. Assume that the NADH produced during the oxidation of ethanol in the reactions above is directly available to the mitochondrial electron transport chain.

c. If you took the number of protons pumped per ethanol molecule calculated in part (b) above and made ATP via the mitochondrial ATP synthase , how many ATP molecules would be generated? The human mitochondrial ATP synthase has 10 C-subunits.

d. A more accurate estimate of the net number of ATP molecules made per ethanol molecule can be obtained by taking into account the total ATP used or created during the metabolism of ethanol (in the oxidation of ethanol to acetyl-CoA and in the TCA cycle). Base your estimate, as the book does for glucose and palmitic acid, on the number of FADH2 and NADH molecules generated during this process. Add or subtract any ATP made or used during the metabolism of ethanol. Assume 1.5 ATP’s made per FADH2 and 2.5 ATP’s per NADH.

Please show work for a-d. thanks.

Intermembrane space (p side) (2x) IV 2H* 4H+ QH2 Matrix (N side) 2H 2H+02 H20 Succinate Fumarate 2H+ 2e- NADH +H NAD

Explanation / Answer

We should approach step by step to answer the questions.

From One molecule of Ethanol ( 2C), we get One molecule of acetyl CoA ( 2C) that then enters the TCA cycle and is oxidized to 2 molecule of CO2 and water.

So we consider metabolism of 1 Acetyl CoA via TCA cycle and subsequently via ET chain for oxidative phosphorylation.

Using TCA cycle, we got 3 (NADH+H+) and 1 (FADH2) from 1 molecule of Acetyl CoA, to be passed on to ETC.

So we need to pass 2 X 3 + 2 = 8 electron through ETC to oxidize each ethanol molecule. [ 2e- for every NADH and 2e- for FADH2. ( Answer of Part a.)

Assume that the NADH produced during the oxidation of ethanol in the reactions above is directly available to the mitochondrial electron transport chain. So they are donating Electron to complex I of ETC.

The transfer of two electrons from each NADH through the respiratory chain to molecular oxygen, paired with four protons are pumped out by Complex I, four by Complex III, and two by Complex IV = 10 in total per NADH

So for 1 acetyl Coa generating from ethanol, we would get 10X3 = 30 proton pumped out of mitochondrial matrix, for 3 (NADH+H+).

As complex II is not pumping electron, we get only 6 H+ pumped out utilizing 2e- donated by FADH2.

So in total 30+6 = 36 protons are pumped in the process of oxidizing ethanol via ETC. ( Answer part b.)

The human mitochondrial ATP synthase has 10 C-subunits. We know that the rotation of the c ring lead to the synthesis of ATP via ATP synthase complex. Each 360-degree rotation leads to the synthesis and release of three molecules of ATP. if there are 10 c subunits in the ring, each ATP generated requires the transport of 10/3 = 3.33 protons, as each c ring is transporting back 1 H+ .

We get 36 H+ pumped out, to be transported back via ATP synthase complex. so the no. of ATP generated with it would be 36 x 3/10 = 10.8 ATP.

[ if we simplify that ATP generation requires the transport of 3.protons ( approx) , then the calculation would be 12 ATP generated via ETC oxidizing 1 molecule of Ethanol.] ( Answer of part c).

Now we need to count total ATP generation from ethanol.

1. Initial phase of Ethanol converted to Acetyl-CoA -- Generation of +2 ATP [ NADH generated in the process are in the microsome and outside mitochondria so not counted for ETC ]

2. Citric acid cycle (inside mitochondria)
2 molecules of adenosine triphosphate are formed from 2 molecules of succinyl CoA -- Generation of +2 ATP

3. Oxidative phosphorylation (inside mitochondria)

1 molecules of FADH2 formed in the citric acid cycle; each ------ Generation of +1.5 ATP
yields 1.5 molecules of ATP

3 molecules of NADH formed in the citric acid cycle; each ------ Generation of +7.5 ATP
yields 2.5 molecules of ATP

So, in total ( 2 + 2 + 1.5 + 7.5 ) = 13 ATP generated net from per ethanol molecule oxidized. ( Answer part d.)

Thanks for asking.

3 molecules of NADH are formed in the oxidation of 1 molecule of each of isocitrate, a-ketoglutarate, and malate 1 molecule of FADH2 are formed in the oxidation of 1 molecules of succinate

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