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Organisms are algorithms - A case of alcohol biochemical pathway

Bio-tech

The famous historian Yuval Nora Halari mentioned "organisms are algorithms" in the main stage of the World Economic Forum in January 2018.[1]

In this article, I want to show that the algorithms exist commonly in software, hardware, and biology (your body) by showing a well-known biological algorithm as a model case. The case is about how alcohol is digested in your body.

My motivation is that I may apply tips for understanding algorithms that I learned in software to understanding algorithms in biology. When I understand the model case of the algorithm, then I am ready to understand other less-known but important biological algorithms. Then if I optimize my input parameters which are foods and environments, considering another input which is my genome, I can optimize my outputs which are my health conditions and my feeling which is one of the results of the health conditions.

Algorithms in software, hardware, and biology

Why do we recognize the common things in software, hardware, and biology? Because people who have been working in software and hardware can utilize their perspective to solve problems in biology. A person who was trained in the medical domain told me that it's difficult to understand biological algorithms because it is very complicated showing a picture of the algorithms in the body. We call biological algorithms biochemical pathways or metabolic pathways.

But the algorithms in hardware that is CAD files or electronic circuit of the hardware is complicated for people except some people working as hardware engineer. And software's source code is complicated for people except for some people working as software engineers in a big software.

As a person who is working on big open-source projects the Ruby language and OpenSSL projects, and seeing other people working for Linux kernel, I believe that there is a way to understand or deal with complicated and big algorithms in biology.

Recently I read the book The Hardware Hacker - Andrew Bunnie Huang[2]. The author is a great hardware hacker. And in the last chapter of the book, he explains his activities in biology. And he mentioned the gaps in recognizing what people feel complicated between not-trained people and trained people in the area of hardware and biology.

Biology - Alcohol biochemical (metabolism) pathway

Let me show you the details of the biological algorithm, again called the biochemical pathway using the example of the alcohol biochemical pathway.

So, this is the picture of the alcohol biochemical pathway.

Alcohol biochemical pathway

The yellow color box means the molecule. If you drink alcohol, the alcohol (ethanol = ethyl alcohol) is converted to acetaldehyde. The acetaldehyde is converted to acetate acetyl-CoA (coenzyme A).

The white color box means the enzyme. In each process between molecules, the enzyme is used as a catalyst to promote the conversion. But if the enzyme has a problem or is less produced for some reason, the conversion doesn't happen well. And the molecule as a source is accumulated in the body. And this causes a problem in the body such as health issues or bad feelings.

The blue color box means gene. There are genes encoding an enzyme. So if a gene has a problem or has variants from the standard gene, it can cause a problematic enzyme.

I introduce some scientific documents and papers.[3][4][5][6]

How I find the molecules and enzymes and genes

This may be a controversial way. But the idea is to get the answer by ChatGPT, or a biology domain-specific generative AIs like BioGPT or BioBert, then to do double-check the answer manually.

I was able to use the ChatGPT free version to get the answer as the alcohol biochemical pathway is well-known.

So, here are the questions I asked the ChatGPT. I double-checked. However, there are still missing parts.

Q1.

Can you show the biochemical pathway of the alcohol metabolism using chemical formula describing the used molecules and enzymes?

A2.

1. Ethanol → Acetaldehyde:
   Enzyme: Alcohol dehydrogenase (ADH)
   Reaction: Ethanol (C2H5OH) + NAD+ → Acetaldehyde (CH3CHO) + NADH + H+

2. Acetaldehyde → Acetate:
   Enzyme: Acetaldehyde dehydrogenase (ALDH)
   Reaction: Acetaldehyde (CH3CHO) + NAD+ + CoA-SH → Acetate (CH3COO-) + NADH + H+ + Acetyl-CoA

3. Acetate enters various metabolic pathways:
   a) Acetate → Acetyl-CoA:
      Enzyme: Acetyl-CoA synthetase or Acetate-CoA ligase
      Reaction: Acetate (CH3COO-) + ATP + CoA-SH → Acetyl-CoA + AMP + PPi

Q2.

What are the genes that produce the enzyme: Alcohol dehydrogenase (ADH), Acetaldehyde dehydrogenase (ALDH), and Acetyl-CoA synthetase or Acetate-CoA ligase in the biochemical pathways above?

A2.

1. Alcohol dehydrogenase (ADH):
  The two primary genes associated with ADH in humans are ADH1 and ADH2. The ADH1 gene family includes ADH1A, ADH1B, and ADH1C, while the ADH2 gene is known as ADH4.

2. Acetaldehyde dehydrogenase (ALDH):
  The primary gene responsible for encoding the acetaldehyde dehydrogenase enzyme is ALDH2. Variants of this gene can affect the activity of ALDH and are linked to variations in alcohol metabolism rates and alcohol sensitivity.

3. Acetyl-CoA synthetase or Acetate-CoA ligase:
   The acetyl-CoA synthetase enzyme is encoded by the ACSS1 and ACSS2 genes in humans. These genes produce different isoforms of the enzyme involved in the conversion of acetate to acetyl-CoA.

My next actions

  • I plan to understand the alcohol biochemical (metabolism) pathway more by understanding missing parts.
  • I plan to apply this way to other biochemical pathways that I am more interested in.

References

  • [1] Will the Future Be Human? - Yuval Noah Harari - https://youtu.be/hL9uk4hKyg4?t=413 (6:53)
  • [2] The Hardware Hacker - Andrew Bunnie Huang
  • [3] LibreTexts Medicine - 9.2: Alcohol metabolism
  • [4] Zakhari S. Overview: how is alcohol metabolized by the body? Alcohol Res Health. 2006;29(4):245-54. PMID: 17718403; PMCID: PMC6527027. - link
  • [5] Jorgenson E, Thai KK, Hoffmann TJ, Sakoda LC, Kvale MN, Banda Y, Schaefer C, Risch N, Mertens J, Weisner C, Choquet H. Genetic contributors to variation in alcohol consumption vary by race/ethnicity in a large multi-ethnic genome-wide association study. Mol Psychiatry. 2017 Sep;22(9):1359-1367. doi: 10.1038/mp.2017.101. Epub 2017 May 9. PMID: 28485404; PMCID: PMC5568932. - link
  • [6] Evangelou E, Gao H, Chu C, Ntritsos G, Blakeley P, Butts AR, Pazoki R, Suzuki H, Koskeridis F, Yiorkas AM, Karaman I, Elliott J, Luo Q, Aeschbacher S, Bartz TM, Baumeister SE, Braund PS, Brown MR, Brody JA, Clarke TK, Dimou N, Faul JD, Homuth G, Jackson AU, Kentistou KA, Joshi PK, Lemaitre RN, Lind PA, Lyytikäinen LP, Mangino M, Milaneschi Y, Nelson CP, Nolte IM, Perälä MM, Polasek O, Porteous D, Ratliff SM, Smith JA, Stančáková A, Teumer A, Tuominen S, Thériault S, Vangipurapu J, Whitfield JB, Wood A, Yao J, Yu B, Zhao W, Arking DE, Auvinen J, Liu C, Männikkö M, Risch L, Rotter JI, Snieder H, Veijola J, Blakemore AI, Boehnke M, Campbell H, Conen D, Eriksson JG, Grabe HJ, Guo X, van der Harst P, Hartman CA, Hayward C, Heath AC, Jarvelin MR, Kähönen M, Kardia SLR, Kühne M, Kuusisto J, Laakso M, Lahti J, Lehtimäki T, McIntosh AM, Mohlke KL, Morrison AC, Martin NG, Oldehinkel AJ, Penninx BWJH, Psaty BM, Raitakari OT, Rudan I, Samani NJ, Scott LJ, Spector TD, Verweij N, Weir DR, Wilson JF, Levy D, Tzoulaki I, Bell JD, Matthews PM, Rothenfluh A, Desrivières S, Schumann G, Elliott P. New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders. Nat Hum Behav. 2019 Sep;3(9):950-961. doi: 10.1038/s41562-019-0653-z. Epub 2019 Jul 29. PMID: 31358974; PMCID: PMC7711277. - link