THIAMINE

Occurrence• Thiamine occurs in the outer

coats (Aluerone) of the seedsof many plants including thecereal grains-

Whole wheat flour

Unpolished hand poundrice

• Yeast is also a very goodsource

• In animal tissues it occursprimarily as the coenzymethiamine pyrophosphate orcocarboxylase.

Conversion of Thiamine to TPP

Thiamine is then converted to its active co-enzymeform, TPP or Cocarboxylase, by addition of twophosphate groups, with the help of ATP.

Catalysed by Thiamine pyrophosphotransferase.

Absorption & Metabolism

• Most absorption of thiamine occurs in jejunum and ileum of the small intestine.

• If consumed in small quantity- thiamine absorbed by sodium dependent active transport mechanism.

• If consumed in large quantity- absorption carried out by passive diffusion.

• TPP within food must be dephosphorylated to thiamine before it can be absorbed by humans. Except in RBCs, where TPP can cross its cell membrane.

• About 80% of thiamine in the body is in the form of TPP.

• Half of the body’s thiamine is in the muscle tissues.

• The body contains no specific storage site for thiamine.

• Thiamine is excreted from the body in the form of thiamine acetic acid and as various other metabolites produced by its degradation.

Biochemical Role of TPP

• TPP is needed for the oxidative decarboxylation ofpyruvate (pyruvic acid) to form the acetyl coenzyme Athat enters the TCA cycle.

• It is also used for the decarboxylation of α –ketogluterate to succinyl coA and CO2 within the TCAcycle.

(Pyruvic acid and α – ketogluterate accumulate inthose with thiamine deficiency)

• It is a co-enzyme of the enzyme transketolase which isrequired for the metabolism of glucose via the hexosemonophosphate shunt (HMP) pathway.

(HMP pathway is the only way by which the body canproduce the ribose and deoxy ribose sugars needed for thesynthesis of ribonucleic acid and deoxy ribonucleic acid)

• Thiamine is involved in the transmission of highfrequency impulses across nerve synapses, the junctionsbetween neighboring nerve cells, across which the signalsare carried by chemical neurotransmitters.

• Thiamine is also known to be involved in the conversionof the amino acid tryptophan to the vitamin Niacin andin the metabolism of the branched- chain amino acidsleucine, isoleucin and valine.

Glucose is incompletely metabolised &pyruvic and lactic acids accumulates inthe tissues and body fluids.

Inability to use glucose efficiently.

Dilates peripheral blood vessels. Ifvasodilatation is extreme, fluid leaks outof the capillaries, producing edema.

High cardiac output- myocardium overworked.

Edema of legs, trunk and face are the mainfeatures. Palpitation, breathlessness anddistended neck is also observed.

Nutritional background issame as wet beriberi.

Degeneration anddemyelination of both sensoryand motor nerves, resulting insevere wasting of muscles.

Symptoms include numbnessin legs, irritability, vagueuneasiness, disorderlythinking and nausea.

It often presents acutelyin alcoholics. Butsometimes seen inpeople with persistentvomiting.

The patient seems quiteconfused. The most valuablesigns are- bilateral,symmetrical opthalmoplegia-paralysis of eye muscles, jerkyrepetition movement of eyeballs.

If left untreated, psychosis isobserved. May also lead todeath.

Occurs in infants between 2and 5 months of age.

Beriberi occurs more often inbreast fed because a lactatingmother’s intake of thiaminemay be too low.

The affected baby developscyanosis, accumulation ofCO2 or lack of O2 in the bloodvessels - skin turns blue,tachycardia is observed.

Recommended Daily Allowance of Thiamine -

NIACIN

Occurrence • Niacin are widely distributed

in plant and animal tissues.

• Meat products are anexcellent source of thevitamin.

• The coenzyme forms of thevitamin are the nicotinamidenucleotide coenzymes;namely, Nicotinamideadenine dinucleotide(NAD+) and Nicotinamideadenine dinucleotidephosphate (NADP+).

Absorption & Metabolism

• Niacin is readily absorbed from the stomach and thesmall intestine.

• It is converted into the coenzymes NAD and NADP withinthe cells and limited stores of these coenzymes are held inthe kidney, liver and brain.

• Any excess niacin is excreted in urine in the forms ofmethyl nicotinamide and methyl carboxamido –pyridone.

Niacin & Tryptophan interrelationship

• About 97% molecules of tryptophan are metabolised inthe major pathway. About 3% molecules are diverted at thelevel of 3- hydroxy anthranilic acid, to form NAD+ .

• The enzyme, Quinolinate phosphoribosyl transferase(QPRT) is the rate- limiting step.

• About 60 mg of tryptophan will be equivalent to 1 mg ofnicotinic acid.

Biochemical role of Niacin

• Its major biochemical role is to form part of thecoenzymes NAD and NADP.

• These coenzymes are required by many of the keypathways of metabolism with NAD being primarilyinvolved in catabolic reactions and NADP functionsmainly in anabolic reactions.

• NAD and NADP act in a large number of reversibleoxidation reduction reactions.

• NAD and NADP participate in more than 200 enzymereactions.

NAD+ dependent enzymes

Lactate dehydrogenase (lactate pyruvate)

Glyceraldehyde-3-phosphate dehydrogenase (glyceraldehyde-3-phosphate 1,3-bisphosphoglycerate)

Pyruvate dehydrogenase (pyruvate acetyl CoA)

Alpha keto glutarate dehydrogenase ( alpha keto gluteratesuccinyl CoA)

Glutamate dehydrogenase (Glutamate alpha ketoglutarate)

Niacin Deficiency

It is an Italian word, meaning “rough skin”.The symptoms are-

Dermatitis: in early stages, bright rederythema occurs, especially in the feet,ankles and face. Increased pigmentationaround neck is known as Casal’s necklace.

Diarrhea: It may be mild or severe withblood and mucus. This may lead to weightloss. Nausea and vomiting may also bepresent.

Dementia: It is frequently seen in chroniccases. Irritability, inability to concentrateand poor memory are more common in mildcases.

Recommended Daily Allowance of Niacin-

References

• Nutrition Science (fourth revised edition) ▫ B. Srilakshmi

• Textbook of Biochemistry for Medical Students▫ D.M. Vasudevan▫ Srikumari S.

• Outlines of biochemistry (5th edition) ▫ Eric E. Conn▫ Paul k. Stumpf▫ G. Bruening▫ Roy H. Doi