Thiamin -- Thiamin diphosphate (TDP)
Adequate Intake ?:
Oxidative decarboxylation of α-keto acids, interconversion of phosphoylated sugars, nervous system functions -- Beriberi = Nervous system and cardiac dysfunction. Major food sources = pork, sunflower seeds, legumes. RDA = 1.12mg
Thiamin is destroyed by prolonged heat.
Some heat is good as cooking can render
thiaminases inactive (such as those found in fish).
Cooking in water can leach out thiamin.
Polyhedroxyphenols such as tannic and caffeic
acids, found in tea and coffee, respectively, have
an oxyreductive effects on thiamine.
Other ATF (anti-thiamin factors) include
mycotoxins (mold) that can occur on some plant
foods such as nuts.
History & Discovery:
Beriberi(Sri Lankan for "weak weak") almost sank the navy in South-East Asia in the 19th century.
Dr Kanehiro suspected that thiamine deficiency was rampant in Japanese Navy due to a diet of white rice.
Christiaan Eijkman described the "anti-beri beri factor" of brown rice in scientific literature in 1887. Chickens fed military left-over rations of white rice: difficulty walking, swollen feet, enlarged heart. Similar syptoms as naval soldiers. Then, a new naval chef decided to ration the rations and Eijkman used a different rice in his experiment. The chickens fed brown rice all recovered within a few days, leading to a Nobel Prize in 1927.
Compound isolated in 1913 by chemist Casimir Funk and called thiamine.
Thiamin is present in phosphorylated form (95%) mainly as thiamin diphosphate (TDP) in animal products.
TDP -> Cleaved -> Thiamin -> THTR1(Enters enterocyte) or THTR2 -> Circulation
Thiamin transporter-1 (THTR1): higher abundance and higher capacity for thiamin transport
Thiamin transporter-2 (THTR2): higher specificity for thiamin.
Thiamin is present as free thiamin in plant products.
Jejunum is primary site of absorption.
Absorption and Storage:
Once inside cells, thiamine is phosphorylated to TDP.
Involved in carbohydrate metabolism through:
branched chain a-keto acid dehydrogenase
Link between glycolysis, the TCA cycle, and the pentose-phosphate pathway
Production of ATP, NADPH, and ribose-5-phosphate which are critical for generating cellular energy and downstream production of amino acids, nucleic acids, and fatty acids.
Transketolase connects the pentose phosphate pathway to glycolysis, feeding excess sugar phosphates into the main carbohydrate metabolic pathways.
Necessary for the production of NADPH (reducing agent usually providing hydrogens), especially in tissues actively engaged in biosyntheses, such as fatty acid synthesis and steroid synthesis by the liver and adrenal glands.
Thiamine is required for the production of ribose, RNA, DNA, nicotinamide adenine dinucleotide (NAD), and adenosine triphosphate (ATP).
Important for organs that rely on glucose for energy: neurons, cardiac myocytes, erythrocytes
Thiamin Diphosphate (TDP): 90%
Thiamin Monophosphate (TMP): 5%
Thiamin Triphosphate (TTP): 5%
Oxidative Decarboxylation of Pyruvate
Pyruvate reacts with TDP (TDP acts as a stabilizer) and is decarboxylated (removes a carboxyl group and releases CO2).
Hydroxyethyl-TDP is formed and transferred to lipoamide (active form of a-lipolic acid) forming acetyl lipoamide.
Acetyl lipoamide reacts with Coenzyme A (CoA), forming acetyl-CoA.
Acetyl-CoA eventually generates ATP through TCA cycle
Thiamin's involvement in Amino Acid Metabolism
Branched chain keto-acid dehydrogenase (BCKAD) uses TDP as its initial catalytic co-factor, eventually feeding into the TCA cycle. Turns isoleucine, leucine, and valine into ATP.
Alpha-ketoglutarate dehydrogenase turns a-ketoglutarate into Succinyl CoA using a TPP, Mg2+ as co-factors
In nerve cells, TTP (5% of total thiamin) is thought to play a role in active ion transport and provides phosphates for the phosphorylation of regulatory proteins involved in activating chloride transport.
Also involved in conversion of pyruvate to acetyl-CoA in the brain, serving as a precursor to acetylcholine and myelin.
Deficiency Diseases, Detection, Cures:
Nausea and vomiting and/or diarrhea
Changes in reflexes
Nervous system - general effects
Thiamin deficiency is rare nowadays as most people meet the RDA (about 95%).
Typical intake is 4.9 mg/day in the US.
Most deficiencies are seen in people who abuse alcohol known as Wernicke-Korsakoff Syndrome.
Prevents absorption of thiamine in small intestine and conversation of thiamin to thiamine diphosphate (TDP).
Also know as thiamine pyrophosphate (TPP).
No known upper level of toxicity--patients with Wernicke-Korsakoff Syndrome often treated with 100-200 mg a day (100 times the RDA).
B1 deficiency results in lesions in the brain; if left untreated irreversible damage occurs. Loss of memory and confusion.