Retinol forms retinoic acid via retinal

Area of Science:

• Biochemistry
• Enzymology
• Nutritional Science

Background:

• Hepatic cytosol possesses alcohol dehydrogenase (ADH) activity.
• Deermice strains exhibit variations in ADH activity, impacting retinol metabolism.

Purpose of the Study:

• To elucidate the enzymatic pathways involved in hepatic retinoic acid synthesis from retinol.
• To determine the role of alcohol dehydrogenase and other retinol dehydrogenases in this metabolic process.

Main Methods:

• Enzyme assays using hepatic cytosol and microsomes from normal (ADH+) and deficient (ADH-) deermice.
• Investigation of retinol conversion to retinoic acid under varying enzyme conditions.
• Isotopic dilution studies to confirm intermediate metabolites.

Main Results:

• Cytosolic ADH+ deermice convert retinol to retinoic acid, while ADH- deermice do not.
• Microsomes alone do not convert retinol to retinoic acid, but do when ADH- cytosol is added.
• Retinal is confirmed as an obligatory intermediate in retinoic acid formation.
• Microsomal retinol dehydrogenase can reduce retinal to retinol, impacting overall retinoic acid production.

Conclusions:

• Retinal is an essential intermediate in the hepatic conversion of retinol to retinoic acid.
• Both cytosolic and microsomal retinol dehydrogenases are critical enzymes in this pathway.
• The interplay between cytosolic and microsomal enzymes regulates retinoic acid biosynthesis.