Introduction

Alcohols are organic compounds defined by the presence of one or more hydroxyl (-OH) groups attached to carbon atoms. This means that several types of alcohols exist—including methanol (wood alcohol) and isopropanol (rubbing alcohol)—these are hazardous and unsuitable for human consumption. In the context of alcoholic beverages, "alcohol" specifically refers to ethanol, the only type that is relatively safely metabolized by humans and responsible for the characteristic effects of drinking, and this safety is dependent on the quantity consumed, as well as individual genetic factors that will be discussed later in this post.

Few words (intro) + history about alcohol

Archaeological evidence shows that humans have been consuming alcoholic beverages for thousands of years, with the earliest known traces dating back to around 7000–6600 BC in ancient China. Today, alcohol is a regular part of life for more than half of the world’s population, integrated into cultural, social, and culinary traditions worldwide. However, ethanol entered the diet of our ancestors much earlier, approximately 10 million years ago, during a period when they were predominantly frugivores consuming naturally fermented fruits. This early exposure to ethanol likely played a significant role in developing specialized molecular mechanisms for as a result shaping the evolutionary adaptations that enable humans to metabolize alcohol today. However, the question is - why do we have a system responsible for alcohol metabolism in our genome if alcohol is toxic ajd not a necessary part of our diet ?

Metabolic pathways of ethanol metabolism and genetics

In humans, ethanol is primarily metabolized in the liver via two key enzymes: alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). When alcohol is consumed in moderation, ADH converts ethanol to acetaldehyde, which is then rapidly broken down by ALDH into acetate—a less toxic compound that can be further utilized for energy.

However, when alcohol intake exceeds the capacity of these enzymes, an alternative pathway called microsomal ethanol oxidizing system (MEOS), involving cytochrome P450 enzymes, becomes more active. This pathway is less efficient and generates more reactive oxygen species, contributing to cellular damage.

Notably, the brain lacks significant ALDH activity, so ethanol metabolism there relies more on catalase, an enzyme that can convert ethanol to acetaldehyde. This difference in enzyme distribution partly explains why acetaldehyde can accumulate in the brain, contributing to the neurological effects of alcohol.

image source

Like other metabolic pathways, the emergence of ADH (alcohol dehydrogenase) is thought to be a result of natural selection. Genetic variations that enhanced the ability to metabolize ethanol likely provided a survival advantage in environments where exposure to naturally fermented fruits was common. Over generations, these beneficial mutations became more prevalent, shaping the efficiency of alcohol metabolism in modern humans.

ADH-ALDH ARE THE MAIN genes/enzymes that are RESPONSIBLE FOR ETHANOL METABOLISM.

ADH1-3 liver

ALDH [...]

Typically, the evolution of metabolic pathways follows a stepwise sequence. For example, to convert Substrate 2 into Substrate 3 using enzyme Y, the organism must first possess a system (gene encoding enzyme X) that enables the transformation of Substrate 1 into Substrate 2.

Substrate 1 --(enzyme X)→ Substrate 2 --(enzyme Y)→ Substrate 3

However evidence suggests that ethanol metabolism evolved in the other way. Same as in an example case ethanol metabolism (to ethanoate) involves two steps:

Meaning that for ethanol to be converted into ethanoate, the organism must first have a system (gene encoding enzyme ADH) that enables the transformation of ethanol into acetaldehyde, and then a second system (gene encoding enzyme ALDH) to convert acetaldehyde into ethanoate.

Recent genetic studies indicate that the ALDH gene family predates the emergence of ADH by several million years. This suggests that the ability to metabolize acetaldehyde was established in our ancestors long before the evolution of efficient ethanol metabolism. As a result, when ADH variants enabling ethanol breakdown appeared, the necessary detoxification pathway for acetaldehyde was already present, reducing the risk of toxic accumulation and facilitating the adaptation to dietary ethanol.

But it is not the only one responsible for alcohol metabolism. There are other systems that are also involved in the process, including cytochrome P450 enzymes (CYP2E1) and catalase. These systems work together to metabolize alcohol and other substances in the body.

Role of ethanol throughout evolution

Their high polarity allows them to be rapidly absorbed into the human body via passive diffusion, beginning in the mouth and continuing throughout the digestive tract

No specialized transporters are required for this process.

ETC

This is a common misconception. The ability to metabolize alcohol is not necessarily an indication that it was vital for survival. In fact, the human body has developed mechanisms to metabolize various substances, including toxins, as a means of detoxification.

However - from an evolutionary perspective, the ability to metabolize alcohol may have provided some advantages in certain environments.

Helped to socialize and bond with others. Alcohol consumption has been associated with social bonding and group cohesion in many cultures. This may have provided an evolutionary advantage by fostering cooperation and social interactions among early humans.

The ability to metabolize alcohol is thought to have evolved (A LONG TIME AGO) as a response to the consumption of fermented fruits and other natural sources of alcohol in the environment.

[Study by](Dudley, R., 2014. The drunken monkey: why we drink and abuse alcohol. Univ of California Press.) (over X million years ago during the period of Frugivory), when traces of various spirits (sugar fermtation) were consumed together with rippened fruits by hunters-gatherers.

Is considered haram (arab) in muslim.

Various reasons for alcohol cosumption. Religion.

Nowadays the amout of ingested ethanol surpases this amount by X.

And if !(this) is true, then why do we have system responsible for alcohol metabolism in our genome?

However the

Populational differences

Asians - mutation in ALDH => (alcohol-related) cancer incidence is higher.

Possible explanation 1 - Hormesis

Possible explanation 2 -

Possible explanation 3

Coincidence because ALDH was already developed at the time Of ADH appearance.

While it may seem that theres no logic behind this, toxicological study suggests that acetaldehyde as a substance is more toxic than ethanol. This means that [...] of ADH wtihout developed ALDH would leave human ancestor organism with ethanol concetration is the blood.

1. At the moment of ADH appearance, metabolism of acetaldehyde was already developed.

Acetaldehyde is more toxic than ethanol!!!

1. Hormesis. Sources of aldehydes in humans organism. In this context ethanol may has served as an aditional source of aldehydes.

study