Liberty University
Biochemistry
BCHM 551
Discussion Board Forum Week 2
In this week's discussion board, you are expected to extensively research and write a comprehensive
essay on the following question;
1. Describe the role of ethanol in cellular energy supply, the metabolism of ethanol (alcohol), the
regulation of its metabolism and the disease conditions associated with its metabolism especially -
hypoglycemia, ketoacidosis, hepatic steatosis, Vitamin deficiency, and acetaldehyde toxicity (you should
feel free to discuss other diseases that are directly related to ethanol metabolism).
Ethanol is composed of molecules that are lipid and water soluble which makes it is easily absorbed
from the intestine. A small percentage of ingested ethanol enters the gastric mucosal cells of the upper
GI tract where it is metabolized. The rest of the ethanol molecules enters the blood. Out of molecules
entering the blood, 85 to 98% is metabolized in the liver, and only 2 to 10% is excreted through the
lungs or kidneys.1 Low amounts of ethanol acts as a carbon source of energy but high levels of ethanol
interfere with mitochondria which is the source of cellular energy. The reason why it acts as a source of
cellular energy is because it is a hydrocarbon. Consumption of alcohol leads to slowing down of
metabolism as it makes the kidneys work slower.
There are several enzymatic pathways that the body uses to metabolize ethanol. The main enzymatic
pathway of ethanol is through hepatic alcohol dehydrogenases which is the conversion of alcohol into
acetaldehyde by the enzyme alcohol dehydrogenase (ADH). Alcohol dehydrogenase exists as a family of
isoenzymes with varying specificity for chain length of the alcohol substrate. ADH is a NAD+-requiring
catalyst communicated at high fixations in hepatocytes.3 Acetaldehyde is then entered in the
mitochondria where it is oxidized into acetate derivation by mitochondrial acetaldehyde
dehydrogenase. A cytosolic acetaldehyde dehydrogenase is in charge of just a minor percentage of
acetaldehyde oxidation. NADH is produced by these reactions and is used to produce ATP through
oxidative phosphorylation. More than 80% of acetaldehyde oxidation in the human liver is catalyzed by
mitochondrial acetaldehyde dehydrogenase. Metabolism of acetate requires activation to acetyl CoA by
acetyl CoA synthetase. In the liver, the isoform of acetyl CoA synthetase is a cytosolic enzyme that
generates acetyl CoA for the cytosolic pathways of cholesterol and fatty acid synthesis.5 Acetate entry
into these pathways is under regulatory control by mechanisms involving cholesterol or insulin. Thus,
most of the acetate generated enters the blood. Most of the acetate enters the blood and is taken up by
skeletal muscles and other tissues, where it is activated to acetyl CoA and is oxidized in the citric acid
cycle.5
Another pathway for ethanol digestion is the microsomal ethanol oxidizing framework (MEOS) which
includes the cytochrome P450 compound CYP2E1 and requires NADPH. Ethanol and NADPH both donate
electrons in the reaction, which reduces O2 to 2H2O. The cytochrome P450 protein contains the binding
sites for O2 and the substrate and carries out the reaction. The enzymes are present in the endoplasmic
reticulum.
Approximately 10 to 20% of ingested ethanol is oxidized through the microsomal oxidizing system
(MEOS). This pathway is used more at people who consume high levels of alcohol because CYP2E1 has a
high Km for ethanol and is inducible by ethanol.
The third pathway includes a non-oxidative pathway catalyzed by unsaturated fat ethyl ester (FAEE)
synthase. This pathway happens fundamentally in the liver and pancreas which are very sensitive to
alcohol.4
Oxidation of ethanol also happen in peroxisomes by means of the movement of catalase. However, this
oxidation pathway requires the nearness of a hydrogen peroxide (H2O2) producing framework and
therefore has no significant part in alcohol oxidation under typical physiological conditions.2
There is a minimal regulation of alcohol metabolism under hormonal control like insulin and glucagon.
Thus, the liver is mainly responsible to oxidize alcohol to remove it from the body.
According to a recent research. humans with small body weight metabolize alcohol at faster rates than
humans with large body weight. These rate of alcohol metabolism correlate with the basal metabolic
rate for the body, indicating that the capacity to oxidize ethanol parallels the capacity to oxidize
nutrients. Alcohol-derived calories are produced at the expense of the metabolism of normal nutrients
since alcohol will be oxidized preferentially over other nutrients.
Several liver diseases can occur as a result of alcohol consumption which are common and can be fatal.
It has three forms: fatty liver, alcohol-induced hepatitis, and cirrhosis. Each may occur alone, or they
may be present in any combination. Alcohol affects liver where it becomes unable to release glucose
into the bloodstream causing hypoglycemia. Consuming too much alcohol can cause diabetes as a result
of ketoacidosis because the acid-base levels in body gets disturbed. Hepatic steatosis is another
condition caused by methanol metabolism deficiency. It happens as a result of alcohol affecting the liver
causing it to be dysfunctional. As a result, the liver become unable to metabolize fat. Alcohol causes a
defect in vitamin and muscle weakness. The liver breaks down excessive alcohol to form acetaldehyde
and causes cirrhosis, ulcers, and metabolic disorders.
Another condition caused by toxic effects of ethanol metabolism is hepatic cirrhosis and loss of liver
function. Liver injury is irreversible at the stage where hepatic cirrhosis develops. At the first stage, the
liver will be enlarged, full of fat, crossed with collagen fibers, and have nodules of regenerating
hepatocytes ballooning between the fibers. As the liver starts losing its function gradually, it becomes
shrunken. During the development of the disease, many of the normal metabolic functions of the liver
are lost. A decrease in the synthesis of blood proteins, including blood coagulation factors and serum
albumin, also occurs. The metabolism of amino groups into urea is decreased, resulting in the
accumulation of toxic levels of ammonia in the blood. Also, the excretion of the bilirubin, a product of
heme degradation, is eliminated, and bilirubin accumulates in the blood where it is deposited in many
tissues, including the skin and sclerae of the eyes.
References:
Wilson, D., & Matschinsky, F. (2020, February 19). Ethanol metabolism: The good, the bad, and the ugly.
Retrieved September 03, 2020, from
https://www.sciencedirect.com/science/article/pii/S0306987720300797
Cederbaum A. I. (2012). Alcohol metabolism. Clinics in liver disease, 16(4), 667–
685. https://doi.org/10.1016/j.cld.2012.08.002
Mezey E. Metabolic effects of alcohol. Fed Proc 1985;44:134–138.
Lieber CS. Medical disorders of alcoholism. New England J Med 1995;33:1058–1065.
Zakhari, S. (2009). Retrieved September 3, 2020, from Overview: How Is Alcohol Metabolized by the
Body?
