Hypoglycemia and Alcohol Intoxication
Alcohol (ethanol) consumption can induce hypoglycemia in individuals low in glucose stores. This is because the human body processes alcohol "preferentially" over the production of glucose. Since the central nervous system (CNS) relies predominantly on glucose for energy, a lack of glucose can lead to permanent brain damage and death.
(Notice the similarity of these molecules. Pyruvate, alanine, and lactate differ only on carbon-2, and ethanol is reduced acetaldehyde.)
Glucose Stores Can Be Exhausted Within 24 Hours When Not Replenished
The entire human body uses approximately 160g of glucose per day with the brain using about 120 of the 160g. The amount of glucose produced per day from glycogen is 190g and the glucose located in bodily fluids is about 20g per day. The total amount of glucose used in one day is almost as much as is produced by the body. So, if a fasting period of a day occurs, or if a period of acute physical exertion occurs, all the glucose available can be used up.
The response of the body to either of these occurences is to increase gluconeogenesis, the biosynthesis of glucose, mainly from the following: lactate produced from glycolysis in skeletal muscle and red blood cells, glycogenolysis in the liver (rate of glucose production is 300 times that of glycogen synthesis in the liver), alanine via the pyruvate-alanine cycle (a.k.a. The Cori-cycle), and other amino acids recieved via the diet or from the breakdown of muscle during starvation.
Because the rate of glycogenolysis in the liver is 300 times faster than glycogen biosynthesis, once the body has utilized its day's supply of glucose, hepatic glucose output becomes dependent on gluconeogenesis. And this is where the crux of the problem lies; alcohol blocks gluconeogenesis.
This means that those who fast or exercise before drinking are most likely to experience hypoglycemia. In particular, malnourished alcoholics are at high risk for this condition. Under these conditions amounts as low as .045 mg/dL can cause hypoglycemia. Embryonic tissue is also dependent on glucose. Hypoglycemia in embryonic tissue inhibits cellular proliferation, so pregnant women should avoid alcohol consumption.
Alcohol Metabolism and Its Effect on Gluconeogenesis
Alcohol is metabolized predominantly in the liver by alcohol dehydrogenase according to the following reaction:
EtOH + NAD+ -----> Acetaldehyde + NADH + H+
The most important thing to notice in this reaction is the production of NADH. The [NAD+]/[NADH] ratio in the cytosol of cells is a major regulatory mechanism. (The "[ ]" indicate concentration.) As the [NADH] increases, the ratio decreases.
The TCA Cycle
Acetyl-CoA production and, thus, the tricyclic acic cycle are inhibited. The [NAD+]/[NADH] ratio decrease inhibits pyruvate dehydrogenase activity and it helps to inhibit the Acetyl-CoA production by increasing the concentration of NADH on the right-hand side of the following equation:
Pyruvate + NAD+ + CoA-SH ----> Acetyl-CoA + NADH + CO2
(Please note that reactions in vivo usually proceed in one direction, but are usually reversible. The reactions have been written in their normal in vivo direction).
The excess NADH slows the TCA cycle, and the build-up of acetyl-CoA stimulates gluconeogenesis (i.e. the production of pyruvate). In addition the excess acetyl-Coa produces ketones which contribute to acidosis in the body.
The Role of NADH
The main effect, however, of the NADH increase and the pyruvate increase in the cytosol is noted by the reversal of the normal in vivo direction of the following reaction:
Lactate + NAD+ ------> Pyruvate + NADH + H+
Due to this lactic acid is produced and lactic acidosis can occur, although it is usually mild.
In addition, alanine from the muscle tissue is transported to the liver mitochondria where it is converted to pyruvate by alanine aminotransferase. In order, oxaloacetate and malate are derived from pyruvate in the mitochondria. The malate is transported out of the mitochondria into the cytosol where it is normally converted back to oxaloacetate from which it continues in gluconeogenesis. This reaction is:
Malate +NAD+ ----> Oxaloacetate + NADH
Notice that this reaction is also inhibited by the excess of NADH in the cytosol. This means that the primary paths for gluconeogenesis (diet, pyruvate, and alanine) are inhibited and that pyruvate is being produced in excess. The body is left with glycolysis for energy production and no glucose for maintenance of critical tissues.
Treatment is to simply administer glucose to the individual. This will completely alleviate the hypoglycemia; however, it will not correct damage to the CNS or embryonic tissue.