Absorption, transport and metabolism of thiamin Domina Petric, MD

Absorption of thiamin I. February 25, 2019 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Two means of uptake Thiamin released by the action of phosphatase and pyrophosphatase in the upper small intestine is absorbed in two ways. At low luminal concentrations (<2 µM) the process is carrier-mediated. At higher concentrations (2.5 mg dose) passive diffusion also occurs. February 25, 2019 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Two means of uptake The active transport mechanism is greatest in the proximal regions of the small intestine. The cells of the intestinal mucosa have a thiamin pyrophosphokinase activity, with a Km about the same as that of the carrier-mediated absorption process. February 25, 2019 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Two means of uptake Most of the thiamin present in the intestinal mucosa is in phosphorylated form. Thiamin arriving on the serosal side of the intestine is largely in the free (nonphosphorylated) form. February 25, 2019 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Transport of thiamin II. February 25, 2019 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Thiamin bound to serum proteins Most of the thiamin in serum is bound to proteins, mostly albumin. About 90% of the total thiamin in blood (5-12 µg/dl) is in erythrocytes. February 25, 2019 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Cellular uptake Thiamin is taken up by cells of the blood and other tissues by active transport. Intracellular thiamin occurs predominantly (80%) in phosphorylated form, most of which is bound to proteins. Thiamin uptake and secretion is mediated mostly by a soluble thiamin transporter that is dependent on Na+ and a transcellular proton gradient. February 25, 2019 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Cellular uptake The transporter has been cloned and mapped to the human chromosome 1q24. The greatest amounts of the transporter have been found in skeletal muscle, heart and placenta. Low or non detectable amounts of transporter have been found in liver, kidney, brain and intestine. February 25, 2019 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Cellular uptake Mutations in the transporter gene are associated with the condition called thiamin-responsive megaloblastic anemia (TRMA). February 25, 2019 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Tissue distribution The adult human stores 25 to 30 mg thiamin, most of which is in skeletal muscle, heart, brain, liver and kidneys. Plasma, milk, and cerebrospinal fluid, and probably all extracellular fluids, contain free (unesterified) thiamin and thiamin monophosphate (TMP), which, unlike the more highly phosphorylated forms (thiamin diphosphate and thiamin triphosphate), appear capable of crossing cell membranes. February 25, 2019 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Tissue distribution In infants, blood thiamin levels decline after birth, owing initially to a decrease in free thiamin, followed by a decrease in phosphorylated forms. February 25, 2019 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Metabolism of thiamin III. February 25, 2019 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Thiamin is phosphorylated in the tissues by two enzymes: Thiamin pyrophosphokinase catalyzes the formation of TPP using ATP. TTP-ATP phosphoryltransferase catalyzes the formation of TTP from TPP and ATP. Thiamin diPhosPhate (TPP) Thiamin TriphosPhate (TTP) February 25, 2019 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Phosphorylation Each of these esters is catabolized by thiamin pyrophosphatase which yields the monophosphorylated product thiamin monophosphate (TMP). February 25, 2019 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Thiamin in excess of that which binds in tissues is rapidly excreted. Catabolism The turnover of thiamin varies between tissues, but it is generally high. Thiamin in excess of that which binds in tissues is rapidly excreted. With an estimated half-life of 10 to 20 days in humans, thiamin deficiency states can deplete tissue stores within a couple of weeks. February 25, 2019 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Catabolism Declines in tissue thiamin levels are thought to involve enhanced degradation of TPP-dependent enzymes in the absence of the vitamin. February 25, 2019 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Urinary excretion Thiamin is excreted in the urine, chiefly as free thiamin and thiamin monophosphate, but also in small amounts as the diphosphate ester and other metabolites. February 25, 2019 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Thiamin metabolites thiochrome thiamin disulfide thiamin acetic acid 2-methyl-4-amino-5-pyrimidine carboxylic acid 4-methylthiazole-5-acetic acid 2-methyl-4-aminopyrimidine-5-carboxylic acid 2-methyl-4-amino-5-hydroxymethylpyrimidine 5-(2-hydroxyethyl)-4-methylthiazole 3-(2′-methyl-4-amino-5′-pyrimidinylmethyl)-4 methylthiazole-5-acetic acid 2-methyl-4-amino-5-formylaminomethylpyrimidine February 25, 2019 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Literature Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. February 25, 2019