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- affect nervous system, in people with excessive consumption of alcohol affect heart and
nervous system and
- deficiency consumption of high carbohydrate low in thiamin (outbreak mulai saat
diperkenalkan rice yang dipolished loss thiamin)
Note: asal tau aja hull, bran, endosperm
- Thiamin structure:

Thiamin diphosphate

- Stability of thiamin:
Unstable to light (bread product walaupun contain significant amount of thiamin,
bisa kehilangan thiamin karna terpapar sunlight saat di display)
Destroyed by sulphites produk kentang yang diblanch by immersion in sulphite
solution almost no thiamin remains
Destroyed by polyphenols tannic acid in tea, betel nuts associated with
thiamin deficiency
Fermented raw fish depleted in thiamin activity of enzyme thiaminase that cleave
the vitamin

Absorption and Metabolism of Thiamin

- most dietary thiamin present as phosphates readily hydrolysed by intestinal
phosphatase FREE THIAMIN readily absorbed in duodenum and proximal jejunum
transferred to portal circulation (as FREE THIAMIN or THIAMIN MONOPHOSPHATE)
- export from mucosal cell active transport (inhibited by alcohol) the reason why
alcoholics are susceptible to thiamin deficiency
- Tissue take up both free thiamin and thiamin monophosphate phosphorylation
thiamin diphosphate (active coenzyme) and thiamin triphosphate
- Excretion some free thiamin excreted in urine, significant amount may lose in sweat;
most urinary excreation as thiochrome (result of non-enzymic cyclisation) as well as variety
of products of side chain oxidation and ring cleavage

Metabolic Funtions of Thiamin

- central role in energy yielding metabolism (esp. metabolism of cacrbohydrate)
- Thiamin diphosphatase / Thiamin pyrophosphate:
coenzyme for three multi-enzyme complexes catalyze oxidative decarboxylation
of substrate linked to reduction of enzyme-bound lipoamide and reduction of NAD +
to NADH: (intinya semuanya enzyme dehydrogenase)
Pyruvate dehydrogenase in carbohydrate metabolism
Alfa-ketoglutarate dehydrogenase in citric acid cycle
Branched-chain keto-acid dehydrogenase involved in metabolism of leucine,
isoleucine and valine
coenzyme for transketolase pentose phosphate pathway of carbohydrate
- Thiamin triphosphate nerve conduction as phosphate donor of phosphorylation of nerve
membrane sodium transport channel
- Little storage of thiamin in body

Thiamin Deficiency
- three distinct syndrome :
chronic peripheral neuritis, beriberi may or may not be associated with heart
failure and oedema (peripheral neuritis tuh yang kayak otot lemah, kejang2 segala, hubungan ke
acute pernicious (fulminating) beriberi (shoshin beriberi) heart failure and
metabolic abnormalities predominate, little evidence of peripheral neuritis (masalah
jantung ama edema, tapi ga kejang keram dsb)
Wernickes encelopathy with Korsakoffs psychosis thiamin-responsive condition
associated especially with abuse of narcotic and alcohol
- Role of thiamin diphosphate as coenzyme of pyruvate dehydrogenase deficiency
caused inability to convert pyruvate to acetyl CoA impaired entry of pyruvate into citric
acid cycle in high carbo diet, caused accumulation of pyruvate and lactate in plasma
life threatening lactic acidosis


- Role in energy-yielding metabolism

- Deficiency rarely fatal efficient conservation and recycling riboflavin in deficiency
- main dietary sources milk and dairy product, as well as eggs(?)
photolysis of riboflavin formation of lumiflavin (in alkaline solution) and
lumichrome (in acidic or neutral solution) biologically inactive
for example exposure of milk in glass bottle to sunlight: luiflavine and lumichrome
catalyze lipid oxidation (lipid peroxides) and methionine to methional
unpleasant flavor (sunlight flavor in milk)
Absorption and Metabolism of Riboflavin
- milk and eggs relatively large amount of free riboflavin
- most food :
riboflavin exist as flavin coenzymes bound to enzymes released when protein is
hydrolysed intestinal phosphatase hydrolysed coenzymes riboflavin absorbed in
upper part of small intestine (much of the absorbed riboflavin) is phosphorylated in
intestinal mucosa by flavokinase enters bloodstream as riboflavin phosphate
- uptake to tissue :
passive carrier-mediated transport of free riboflavin metabolic trapping by
phosphorylation to riboflavin phosphate onward metabolism to FAD
FAD (not protein bound) rapidly hydrolysed (by nucleotide pyrophosphate)
unbound riboflavin phosphate hydrolysed to free riboflavin (non-specific
phosphatase) diffuses out of the tissues into bloodstreeam
- Excretion:
Riboflavin and riboflavin phosphate that are not bound to protein plasma filtered
at the glomerulus
Renal tubular reabsorption saturated at normal plasma level
Active tubular secretion of vitamin
Urinary excretion after high dose 2 or 3 folds freater than glomerular filtration
- Storage and Conservation:
No significant storage surplus intake is excreted rapidly
Efficient conservation of tissue riboflavin in deficiency:
Only loss of riboflavin from tissues only small amount from the coenzymes
that is bound covalently to the enzyme
The coenzymes that is bound non-covalently are recycled when protein are

Metabolic Functions of the Flavin Coenzymes

- Role of flavin coenzymes:
electron carriers in various redox reactions central to all metabolic processes,
including mithochondrial electron transport chain
key enzymes in fatty acid and amino acid oxidation, citric acid cycle
- most flavoproteins:
have FAD as prosthetic group
have both FAD and riboflavin phosphate
some have other prosthetic group as well
- reoxidation of reduced flavin in oxygenases and mixed function oxidases by way of
formation of flavin radical and flavin hydroperoxide with intermediate generation of
superoxide and perhydroxyl radicals and hydrogen peroxide flavin oxidases make
significant contribution to total oxidative stress in body
Riboflavin Deficiency
- deficiency is not fatal, due to this reasons:
vitamin is widespread in food, most diets will provide adequate amount of vitamins
to permit maintenance of central metabolic pathways
efficient re-utilisation of riboflavin released by turnover of flavoproteins, with only
small amount is excreted or catabolised
- main metabolic effect of riboflavin deficiency lipid metabolism (lower metabolic rate in
lipid metabolism)
- deficiency characterized by:
angular stomatitis (lesions at corners of mouth)
cheilosis (lesions by margin of lips)
magenta tongue (desquamation of tongue red, dry, atrophic)
sebhorreic dermatitis


- not strictly vitamin can be synthesized from amino acid tryptophan, except when the
metabolism of tryptophan is deranged dietary niacin is important
- major dietary source of niacin meat
- structure:

- nicotinamide ring of NAD can be synthesized from the essential amino acid tryptophan
- 60 mg of tryptophan = 1 mg preformed niacin, this ratio may changed due to to hormonal
- calculation for niacin content of food mg preformed niacin + 1/60 mg tryptophan (ignore
preformed niacin in cereal)
- Niacin in cereals:
Bound as niacytin-nicotinoyl esters to polysaccharides, polypeptide, and
glycopeptides biologically unavailable
Up to 10% niacin in niacityn may be available for absorption due to hydrolysis
activity of gastric acid
Treatments with alkali (e.g CaOH for overnight) release nicotinic acid
Absorption and Metabolism of Niacin
Free Niacin
- dietary source meat
- niacin usually present in tissues (therefore in foods) as nicotinamide nucleotide coenzymes
- post mortem rapid hydrolysis of NAD(P) free nicotinamide
- nicotinic acid and nicotinamide absorbed from small intestine by sodium-dependent
saturable process
Nicotinamide Nucleotide Coenzymes
- synthesized from : niacin vitamers , quinolinic acid (intermediate in metabolism of
- In liver: oxidation of trypthophan considerably greater synthesis of NAD than required
catabolized nicotinic acid and nicotinamide taken up by other tissues for
synthesis of coenzymes
- Catabolism of NAD :
Catalyzed by four enzymes :
NAD glycohydrolase (release nicotinamide and ADP-ribose)
NAD pyrophosphatase (release nicotinamide mononucleotide)
Poly (ADP-ribose) polymerase
Activation ADP-ribosyltransferase and Poly (Poly-ribose) polymerase by toxin that
cause DNA damage considerable depletion of intracellular NAD(P) + provide
suicide mechanism (ensure that cells that suffer very severe damage, as result of
NAD(P) depletion, will die) impaired ATP synthesis
Administration of DNA-breaking carcinogen excretion large amounts of
nicotinamide metabolites and depletion of tissue NAD(P)
Chronic exposure to mycotoxins and carcinogens pellagra (when intake of
tryptophan and niacin are marginal)
- Excretion
no urinary excretion of nicotinic acid and nicotinamide in normal condition
both vitamers are actively reabsorbed from glomerulus
significant excretion intake is really high that the transporter is saturated

Synthesis of Nicotinamide Nucleotides from Tryptophan

- Dietary intake of tryptophan:
Small amount used for net new protein synthesis (e.g serotonin)
Small amount used for synthesis of 5-hydroxy tryptophan
Most metabolized by the oxidative pathway potentially available for NAD
- Liat kertas lain

Metabolic Functions of Niacin

- oxidation and reduction reactions as the functional nicotinamide part of the coenzymes
NAD+ involved as electron acceptor in energy-yielding metabolism, oxidized by
mitochondrial electron transport chain
NADPH major coenzyme in reductive synthesis reactions
Exception: pentose phosphate pathway of glucose metabolism reduction of
NADP+ to NADPH, source of half the NADPH required for fatty acid synthesis
- Source of ADP-ribose for:
Poly (ADP-ribose) polymerase

Pellagra Disease of Tryptophan and Niacin Deficiency

- Symptoms (3D):
Dermatitis photosensitive dermatitis (severe sunburn affecting body parts
exposed to sunlight)
Dementia due to reduced synthesis of neurotransmitter serotonin (synthesized
from serotonin)
- Untreated pellagra fatal
- Other factor may contributed:
Deficiency of riboflavin impaired activity of kynurenine hydroxylase
Deficiency of vitamin B6 impaired activity of kynureninase
The reasons above matters when the intake of tryptophan and niacin are marginally


- generic descriptor includes 6 vitamers :

alcohol pyridoxine (+ their 5-phosphates)
aldehyde pyridoxal (+ their 5-phosphates)
amine pyridoxine (+ their 5-phosphates)
- those vitamers are interconvertible, have equal biological activity converted inside the
body pyridoxal phosphate (metabolically active form)
- 4-pyridoxic acid biologically inactive end product of vitamin B6 metabolism
- foods heated pyridoxal and pyridoxal phosphate react with -amino groups of lysine
Schiff base vitamin B6 and lysine biologically unavailable
Absorption and Metabolism of Vitamin B6
- phosphorylated vitamins hydrolysed by alkaline phosphatase in intestinal mucosa
absorbed rapidly by diffusion phosphorylated pyridosine phosphate and
pyiridoxamine phosphate oxidized pyridoxal phosphate
- (much of) the ingested vitamin released into portal circulation as pyridoxal after
dephosphorylation at mucosal cell
- Tissue uptake:
Liver: enter liver by diffusion metabolic trapping (as phosphates)
Out from liver : pyiridoxal phosphate and some pyridoxal exported from the liver
bound to albumin, remaining free pyridoxal oxidized and excreted
Extrahepatic tissue: tissues take up pyridoxal and pyridoxal phosphate pyridoxal
phosphate hydrolysed (by extracellular alkaline phosphatase) pyridoxal, so can
cross membrane trapped by phosphorylation
80% total body vitamin B6 is pyridoxal phosphate in muscle associated with
glycogen phosphorylase