Absorption of vitamins, iron and calcium

Vitamin B12 (cobalamin) takes a multistep route. Pepsin and acid release it from food proteins. In the stomach it binds haptocorrin (R-binder) from saliva, which protects it from acid. In the duodenum, pancreatic proteases digest the haptocorrin, and B12 transfers to intrinsic factor (IF) from parietal cells. The IF–B12 complex resists digestion and binds the cubilin–amnionless receptor (cubam) in the terminal ileum, where it is endocytosed. B12 leaves the enterocyte on transcobalamin II. The liver stores about 2–5 mg, enough for several years at a requirement of about 2.4 µg a day, so deficiency develops slowly.

Iron is absorbed mainly in the duodenum. Non-haem Fe³⁺ is reduced to Fe²⁺ by duodenal cytochrome b (Dcytb); acid and vitamin C help this step. Fe²⁺ enters with H⁺ through DMT1. Haem iron is taken up separately (HCP1) and is absorbed more efficiently. Inside the cell, iron is either stored as ferritin, and lost when the cell is shed, or exported through basolateral ferroportin. Hephaestin re-oxidises it to Fe³⁺ for binding to transferrin. Hepcidin, from the liver, binds ferroportin and causes it to be degraded. This is the master regulator: hepcidin falls in iron deficiency and rises in inflammation and iron overload. Only about 1–2 mg of iron is absorbed each day, which matches losses, because the body has no regulated excretory route for iron.

Calcium is absorbed by two routes. Active transcellular uptake in the duodenum uses apical TRPV6 channels, the intracellular carrier calbindin-D9k, and basolateral PMCA1b and NCX1 pumps. It is upregulated by calcitriol (1,25-(OH)₂D). Passive paracellular uptake occurs along the whole small intestine and is quantitatively large in the jejunum and ileum. Phytate, oxalate and fat malabsorption (calcium soaps) reduce absorption.

Folate polyglutamates are cleaved to monoglutamates by brush-border folate conjugase and absorbed in the jejunum by the proton-coupled folate transporter. Most other water-soluble vitamins have specific carriers in the proximal small intestine. Fat-soluble vitamins (A, D, E, K) depend on micelles and chylomicrons.