1. How does alcohol enter the blood? 2. How do we build/become a tolerance?

Question

Thank you EtOHRx you are very informative. I thought for a minute I would be stuck with that little boy's answer.

Answer 1

Oops

Answer 2

Following ingestion, about 25% of the ethanol is rapidly absorbed through the stomach wall. At first, absorption is rapid but then the rate decreases even if gastric concentrations remain high. Absorption of alcohol through the small intestine is extremely rapid.

Elimination:

Ninety to 98% of the ingested drug is completely oxidized.  The small amounts that remain are excreted unchanged in the breath, urine and sweat.  Blood levels fall some 15 mg% per hour (about 7.5 - 8.5 grams/hour) regardless of initial alcohol conc.

The rate-limiting reaction:

CH3--CH2--OH + NAD+ ---> CH3--CHO + NADH + H+

ethanol acetaldehyde

This process occurs mainly in the liver:

The major hepatic enzyme catalyzing this reaction is ALCOHOL DEHYDROGENASE.

ADH properties:

- zinc dependent enzyme

- uses a coenzyme (NAD+)

- apparent Km (affinity) = 0.5 to 2.0mM

- broad spectrum of reactants

- can be inhibited by pyrazole

Note: ADH functions to oxidize the ethanol normally produced by the intestinal flora.

A couple of sites that are a bit better at explaining.

http://www.forcon.ca/learning/alcohol.ht...

http://www.chemcases.com/alcohol/alc-04....

[Lester and colleagues estimated that humans and most mammals produce about 12 to 40 grams of alcohol per day without even drinking!! ]

Tolerance

The acquired ability to consume large quantities of alcohol common in alcoholism results from adaptations in the CNS and increased capacity of elimination by liver enzymes.

More recently discovered was the hepatic microsomal system (found in the smooth ER or endoplasmic reticulum of liver cells). In particular, the membrane-bound cytochrome P-450 (Km of 8-9mM) is important.

In alcoholics, there is a marked induction of smooth ER in liver cells: