The Answer

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Figure 2: Flowchart of ethanol metabolism

When alcohol, in the form of ethanol, is consumed, the majority enters the systemic circulation where it can then be metabolized in the liver via the enzyme alcohol dehydrogenase (ADH). ADH, as well as cytochrome P450 (CYP2E1) and catalase to lesser extents, are responsible for the oxidation of ethanol, which removes around 90% of the ethanol absorbed in the body. ADH oxidizes ethanol to acetaldehyde, while reducing NAD+ to NADH, which is then oxidized to acetate by the enzyme aldehyde dehydrogenase (ALDH), reducing another equivalent of NAD+ to NADH. The acetate produced via ALDH in the liver is then transported to peripheral tissues where it is converted to Acetyl-CoA. Therefore, the carbon atoms entering the body in ethanol are ultimately incorporated into the same product as the breakdown pathways of proteins, carbohydrates, and fats (3).

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Figure 3: Alcohol dehydrogenase (ADH-1) is depicted above  (4). Located in the cytosol of the liver, ADH is a dimeric enzyme with a zinc center in both 40 kDa subunits, shown in red. There are 6 classes of ADH, but class 1 ADH forms (containing the genes ADH1, ADH2, and ADH3) are those that catalyze the oxidation of alcohol.

 

 

3 Comments

  1. I like how concise the ethanol metabolism explanation is. Great summary!
    – For Figure 3, it might be helpful to include in the caption what the green and red ADH domains represent. I’m assuming the red is the Zinc centers but it’s not explicitly stated.
    – Figure 4 is a little overwhelming. Could it be simplified at all? My suggestion would be highlighting the most important enzymes and intermediates in order to make the diagram easier to follow.

  2. I agree that I like how concise your “answer” page is!

    Figure 2 is good, and I like the simplified summary of ethanol metabolism. However, the way it is now, there is no distinction between enzymes and intermediates in the pathway. For example, ALDH is an enzyme that produces an intermediate, acetate, but I would have thought they were both intermediates. Perhaps you could show each intermediate structure (especially that of ethanol, which I think is important) and put the enzyme names beside each arrow. This would easier distinguish between the two. Showing the reductions of NAD+ to NADH may also be beneficial in this diagram.

    I agree with Ioana that Figure 4 is a bit overwhelming. Especially without much of a caption, I don’t think it adds very much to this overview page. I think it should either be simplified to show the most important aspects (and explained), or not included on this particular page.

  3. Nice and concise indeed!

    Perhaps touching on how cytochrome P450 and catalase differ from alcohol dehydrogenase would help clarify Figure 2 – maybe include why these alternate pathways exist (location?) and how their intermediates differ (if that information is even out there.)

    I also noticed that in your “Question” page, you asked why certain drugs can’t be taken with alcohol, while this page did not answer that. I do like that second part of your question – it’d be very interesting to learn – but if you think you have enough information already, then maybe you should get rid of that second question.

    I also agree with my partners in that highlighting some important compounds/intermediates in Figure 4 would help guide the reader’s eyes. Maybe highlighting a certain pathway of interest would help visually, though the only compounds you seem to focus on are ethanol, ADH and acetaldehyde, and this is more of a precursor pathway to a bunch of other pathways. Even so, a little highlighting of this precursor pathway might make it easier to see where the acetaldehyde and reducing power of ADH go.

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