Breakdown by carnosinase

This page summarises the enzymes. The full discussion of what they mean for oral dosing is at Carnosinase and absorption.

Two enzymes

• Serum carnosinase (CN1, gene CNDP1) circulates in blood. It is a zinc-dependent enzyme of the M20 metalloprotease family. In humans it is made in the brain and reaches the blood through cerebrospinal fluid (Separations 2023 review).
• Tissue carnosinase (CN2, gene CNDP2) works inside cells and is a non-specific dipeptidase (Bellia 2014).

Humans are unusual

Serum CN1 is found in humans and other higher primates. Most other mammals, including rats and mice, have no serum CN1. The golden hamster is the exception among common laboratory animals. This is why rodent supplementation studies do not carry over cleanly to people: oral carnosine reaches rodent tissues intact and reaches human tissues largely as beta-alanine and histidine (Separations 2023 review).

Variation between people

Serum CN1 activity varies widely. Drivers include a repeat polymorphism in the CNDP1 gene, the amount of enzyme in serum, and age. Low CN1 activity has been linked to a lower risk of diabetic kidney disease, which is why the gene appears in kidney research. See Kidney.

Getting around the enzyme

Researchers have made carnosinase-resistant forms (carnosinol, D-carnosine), prodrugs and a CN1 inhibitor called carnostatine (Separations 2023 review). N-acetylcarnosine resists the enzyme better than carnosine. Anserine, with a methyl group on the ring, is broken down more slowly.