MANTERANDGATZ 1

VITAMINS

VITAMINS
Organic nutrients
Needed in small amounts only
Cannot be synthesized in the body. Except: VITAMIN D
No caloric value
Groups of vitamins:
o FAT SOLUBLE VITAMINS
Characteristic: Apolar/hydrophobic/non-polar
Requires: fat
Storage: Stored in the liver & adipose tissues
Can cause: toxicity since it is stored
Excretion: stool
o WATER SOLUBLE VITAMINS
Characteristic: Polar
Requires: lipoproteins
Storage: Not stored (Except: vitamin B12 which is stored in the liver)
Can cause: deficiency since it is not stored
Excretion: urine
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THIAMINE
Aka:
o anti-neuritic vitamin
o aneurin
Co-enzyme form: THIAMINE PYROPHOSPHATE (TPP)
Method of Detection: THIAMINE THIOCHROME (BLUE)
o Add postassium ferricyanide
o Intensity of blue color determines the amount of thiamine
Requirement daily intake:
o Thiamine intake = carbohydrate intake / caloric intake
o 0.5 mG OF THIAMINE PER 1000 CALORIES
o Increase in carbohydrate intake = increase thiamine requirement
o Increase in fat intake = decrease thiamine requirement
Functions:
o DECARBOXYLATION OF PYRUVATE
Via: pyruvate dehydrogenase complex
Cofactors needed: TPP, CoASH (vit b5), NAD, FAD
Deficiency of B1 will inhibit pyruvate dehydrogenase complex. Reaction will not proceed to
krebs cycle. So, less ATP will be produced.
o DECARBOXYLATION OF ALPHA-KETOGLUTARATE
Via: krebs cycle
Cofactor needed: TPP
Deficiency of B1 will inhibit the conversion of alpha-ketoglutarate to succinyl CoA. So, no ATP
will be formed
o TRANSKETOLASE REACTION
Via: HMP shunt
Enzyme that requires B1: transketolase (can be assayed to detect if B1 is present)
Reactant: pentose sugars (ribose & xylulose)
Transketolation reaction transfers 2 carbons from ribose to xylulose. Ribose will become
glyceraldehyde and xylulose will become 7 carbon sugar.
Deficiency of B1 will inhibit transketolation. So kung walang transketolation, ung ribose mo
hindi macoconvert, magaacumulate ngayon ung pentose sugars.
o METABOLISM OF NERVE TISSUES
Via: thiamine triphosphate (TTP)
Deficiency of B1 will impair metabolism of nerve tissues. So, a decrease in the metabolism of
nerve tissue can cause neurologic manifestation (simple prick sensation, numbness, paralysis)
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VITAMINS

Manifestation of Deficiency:
o SEVERE MUSCLE WEAKNESS
Rationale: pyruvate is not converted to acetyl-CoA which is needed for krebs cycle. So no krebs
cycle, there will be less ATP production.
Affects both: skeletal & cardiac muscle
o LACTIC ACIDOSIS
Rationale: since pyruvate is not converted to acety-CoA, pyruvate may undergo lactic acid
production.
o PENTOSEMIA / PENTOSURIA
Rationale: transketolation cannot take place. So, pentose sugars tends to accumulate
o NEUROLOGIC MANIFESTATION
Rationale: metabolism of nerve tissue is inhibited due to lack of thiamine triphosphate

Conditions that predisposes manifestation of deficiency:

o IF CALORIC INTAKE IS DEPENDENT FROM CARBOHYDRATES
Rationale: kung mas mataas ang carbohydrate intake, mas maraming thiamine ang kelangan.
So kung matakaw ka sa kain, nauubos ang thiamine present sa katawan. So it can contribute
to deficiency.
o ANTI-THIAMINE FACTORS FOUND IN RAW FOODS
Rationale: they contain thiaminase that destroys thiamine
o PREGNANCY AND LACTATION
Rationale: increase thiamine requirement during these periods
o HARD PHYSICAL LABORERS
Rationale: more active body requires an increase in caloric intake. Increase in caloric intake will
increase thiamine requirement.
o RETIREMENT AGE
Rationale: decrease in the capacity to absorb thiamine. So decrease in absorption of thiamine
requires increase thiamine intake to compensate for the decrease in absorption
o INCREASE BODY METABOLIC RATE
Rationale: increase metabolic states will increase thiamine requirement

Clinical significance of thiamine deficiency:

o BERI-BERI
Adult beri-beri
CHRONIC PERIPHERAL NEURITIS TYPE
o Dry type of adult beriberi (neurological)
o Most common
o Without cardiac failure
FULMINATING/PERNICIOUS/SHOSHIN BERIBERI TYPE
o Wet type of adult beriberi (cardiac involvement and pitting edema)
o Most fatal
o With cardiac failure
MIXED

Infantile beri-beri
APHONIC TYPE
o Manifests laryngeal paralysis
PSUDOMENINGITIC TYPE
o Convulsive seizures without fever
CARDIALGIC TYPE
o Baby manifests cyanosis

o WERNICKES KORSAKOFF SYNDROME

Common in: chronic alcoholics
Rationale: Alcohol damages the lining of intestines. So decrease ang absorption ng thiamine.
Manifestation: mental retardation, ataxia, opthalmoplegia
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VITAMINS

RIBOFLAVIN
Aka:
o lactoflavin
o vitamine G
Co-enzyme form:
o FLAVINE ADENINE DINUCLEOTIDE (FAD)
o FLAVINE MONO NUCLEOTIDE (FMN)
Best source: MILK
Function:
o HYDROGEN TRANSFER REACTIOn (oxidation-reduction reaction)
Involvement of: isoalloxazine ring or flavine ring (active form of FAD and FMN)
o CONVERSION OF SUCCINATE TO FUMARATE
o DECARBOXYLATION OF PYRUVATE
o DECARBOXYLATION OF ALPHA-KETOGLUTARATE
o URIC ACID SYNTHESIS (hypoxanthine urate)
o GLYCONEOGENSIS (glycerophosphate dihydroxyacetone phosphate)
o HMP SHUNT (for Glutathione reductase to reduce glutathione to act as antioxidant)

Manifestation of deficiency:
o EPITHELIAL CHANGES IN ORAL CAVITY
Cheilosis or perleche (angular stomatitis)
Present in all B complex deficiency not only in B2 deficiency
Treatment is B complex
Magenta tongue (glossitis)
o CORNEAL VASCULARIZATION
o SEBORRHEIC DERMATITIS
o PHOTOPHOBIA

NIACIN
Aka: pellagra preventive factor
Co-enzyme form: NAD AND NADP
Synthesis:
o Precursor: TRYPTOPHAN
o Via: KYNURENINE-ANTHRANILATE PATHWAY
o Co-enzyme needed: VITAMIN B2 & B6
o TRYPTOPHAN LOAD TEST
Determines: B6 deficiency
Result: increase levels of xanthurenic acid
Explanation: if xanthurenic acid levels increases, B6 is deficient, then, no niacin production.
o Deficiency of B2 & B6 can manifest pellagra because tryptophan is not converted to niacin

Large doses can cause an increase production of HISTAMINE

Function:
o Co-enzyme for 3 enzymes of kreb cycle
MALATE DEHYDROGENASE
ALPHA-KETOGLUTARATE DEHYDROGENASE
ISOCITRATE DEHYDROGENASE
o Co-enzyme for GLUCONEOGENESIS (lactate pyruvate glucose)
o Co-enzyme for KETOGENESIS (hydroxybutyrate gluconate)
o Co-enzyme for GLUCORONIC ACID PATHWAY (glucose gluconate)
o Co-enzyme for OXIDATIVE DEAMINATION OF GLUTAMIC ACID (glutamate alpha ketoglutarate)

3Ds of pellagra:
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VITAMINS

o DERMATITIS
Found only in: skin exposed to sun (except: FACE)
Manifestation:
Cassals necklace
Gloves and stockings lesion
o DIARRHEA
o DEMENTIA
MAL DE LA ROSA
o Early lesion seen in the skin of pellagra
o Seen as red to pink colored lesion

BLACK TONGUE
o This is seen in the tongue of animals that are deficient to niacin

Diseases with pellagra despite of adequate tryptophan:

o HARTNUPS DISEASE
Deficiency of: tryptophan pyrrolase
o CARCINOID SYNDROME
Overproduction of: serotonin
Serotonin causes diversion away from NAD synthesis

PYRIDOXINE/PYRIDOXAL/PYRIDOXAMINE
Aka:
o amino acid metabolism vitamin
o rat acrodynia factor
o vitamin Harris
o anti-dermatitis vitamin
Co-enzyme form: PYRIDOXAL PHOSPHATE (PLP)
Functions:
o DECARBOXYLATION OF GLUTAMIC ACID TO GABA
GABA is a natural tranquilizer
o CONVERSION OF KYNURENINE TO ANTHRANILIC ACID
This reaction is needed for conversion of tryptophan to niacin
o CONVERSION OF HOMOCYSTEINE TO CYSTEINE
Homocysteine is corrosive to the lining of blood vessels (so dapat di sya magaacumulate.
How?)
Ways to prevent accumulation of homocysteine:
Vitamin B6 and cystathione synthetase
o Converts homocysteine to cysteine
Vitamin B9 and B12
o Converts homocysteine to methionine
o Co-enzyme in CARBOHYDRATE & FAT METABOLISM
Linoleic arachidonic reaction
Glycogenolysis (enhance activity of phosphorylase)
o Co-enzyme for TRANSAMINATION
o Co-enzyme for HEME SYNTHESIS (glycine delta-aminolevulinic acid)
o ENERGY PRODUCTION FROM AMINO ACID
o CONVERSION OF TRYPTOPHAN TO SEROTONIN

Manifestation of B6 deficiency:
o CONVULSIVE SEIZURE
Rationale: decrease or no production of GABA
o PELLAGRA LIKE SYMPTOM
Rationale: kynurenine to anthranilic acid reaction did not take place. So no niacin production.
o HYPOCHROMIC MIRCOCYTIC TYPE OF ANEMIA
Rationale: decrease production of delta aminolevulinic acid
o CARDIOVASCULAR DISEASES
Rationale: accumulation of homocysteine that damages the lining of blood vessels.
o GIT MANIFESTATION (abdominal pain, diarrhea, vomiting)
Rationale: decrease production of serotonin
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VITAMINS

o FORMATION OF OXALATE STONES

Rationale: glyoxalate is converted to oxalic acid (dapat glyoxylate to glycine)
Vitamin C can also give this manifestation of oxalate stones when given in high doses
o ACRODYNIA IN RATS

PANTHOTHENIC ACID
Aka: everywhere vitamin
Essential component of: COENZYME A / COACETYLASE
Richest source: ROYAL JELLY IN BEEHIVES
Forms:
o ACETYL COA
Involved in the 1st reaction of krebs cycle
Acetyl CoA + oxaloacetate = citric acid
Involved in Cholesterol & steroid synthesis
Prevents atrophy of adrenal gland
o SUCCINYL COA
Involved in heme synthesis
Glycine + succinyl CoA = heme
o ACYL CARRIER PROTEIN
Involved in extramitochondrial lipogenesis for Synthesis of fatty acid

Manifestation of panthothenic acid deficiency:

o EASY FATIGABILITY + CARDIOVASCULAR DISTURBANCES + MENTAL DEPRESSION
Rationale: decrease formation of citric acid needed in the krebs cycle resulting to low ATP
production
o MICROCYTIC HYPOCHROMIC ANEMIA
Rationale: decrease heme synthesis due to lack of succinyl CoA
o DECREASE CHOLESTEROL BLOOD LEVEL
Rationale: decrease lipogenesis due to lack of acyl carrier protein

BIOTIN
Aka:
o vitamin B7
o Anti-egg white injury factor
Abundant in: EGG YOLK
Inhibitor: AVIDIN
Binding site of biotin in an enzyme: LYSINE (biotin + lysine = BIOCYTIN)
Function:
o CARBOXYLATION REACTION / CARBON DIOXIDE FIXATION
acetyl CoA malonyl CoA
pyruvic acid oxaloacetic acid (anaphlerotic reaction)
purine synthesis in carbon no. 6
formation of carbamoyl phosphate sythethase in urea cycle

manifestation of biotin deficiency:

o IN HUMANS:
alopecia
early graying of hair
mental depression and hallucination
o IN RATS:
spectacle-eyed appearance
kangaroo posture
alopecia
retarded growth
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VITAMINS

FOLIC ACID
co-enzyme form: TETRAHYDROFOLAIC ACID (THFA / FH4)
o activation of folic acid:
1st reduction step:
FOLIC ACID DIHYDROFOLIC ACID
Enzyme: dihydrofolate reductase
Reducing agent: NADPH
Co-enzyme: vitamin C

2nd reduction step:

DIHYDROFOLIC ACID TETRAHYDROFOLIC ACID
contains: GLUTAMIC ACID + PARAAMINOBENZOIC ACID
requirement daily: 400MG
active parts: N5 AND N10 (points where you add 1 methyl group)
most abundant form of folic acid: N5 METHYL FOLIC ACID
Forms of folic acid:
o N10 FORMYL THFA: provides C2 of purine ring
o N5 N10 METHENYL THFA: provides C8 of purine ring
o N10 HYDROXYMETHYL THFA: for thymine synthesis
o N5 FORMIMINO THFA: for histidine catabolism
Function:
o FOR SYNTHESIS OF PURINES AND PYRIMIDINES FOR DNA SYNTHESIS
o MATURATION OF RED BLOOD CELLS
o CONVERSION OF HISTIDINE TO GLUTAMIC ACID
product of histidine metabolism: urocanic acid
urocanic acid is converted to formimino glutamic acid (FIGLU)
FIGLU is converted to glutamic acid via folic acid
If folic acid is deficient, FIGLU will be excreted in the urine rather than converted to glutamic
acid
The presence of FIGLU in the urine is the basis of FIGLU EXCRETION TEST / HISTIDINE
LOAD TEST
Causes of folic acid deficiency:
o DIET
o INTESTINAL ABSORPTION
o EXCESSIVE DEMANDS OF TISSUES
o METABOLIC DERANGEMENTS
Manifestation of folic acid deficiency:
o MACROCYTIC MEGALOBLASTIC ANEMIA
Rationale: no DNA synthesis for maturation of RBCs due to lack of purine and pyrimidine
no NEUROLOGICAL SYMPTOMS
o PANCYTOPENIA
Definition: low count of RBC, WBC, Platelets
Can cause bleeding and infection
o GROWTH FAILURE
o ACHROMOTRICHIA IN RATS (absence of normal pigmentation)
Drugs that may interfere with folate metabolism:
o ANTICONVULSANTS (increases catabolism of folic acid)
o ORAL CONTRACEPTIVE & ESTROGEN

METHTOTREXATE
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VITAMINS

o Aka: double bladed drug

o Folic acid antagonist
o Inhibits: dihydrofolate reductase
o Decrease in folic acid reductase no activation of folic acid no purine and pyrimidine synthesis
no DNA

CYANOCOBALAMIN
Aka:
o anti pernicious anemia vitamin
o extrinsic factor of Castle
o erythrocyte maturation factor
ONLY VITAMIN NOT FOUND IN FRUITS AND VEGETABLES
INTRINSIC FACTOR: needed for absorption that is found in the stomach
Contains: CORRIN RING SYSTEM WITH COBALT IN THE CENTER (similar to porphyrin ring of heme)
Co-enzyme form: 5DEOXYADENOSYLCOBALAMINE (biological Grignard reagent/cobamide coenzyme)
Functions:
o INVOLVED IN METABOLISM OF ODD NUMBER FATTY ACID
o CONVERSION OF HOMOCYSTEINE TO METHIONINE
o CONVERSION OF RIBOSE TO DEOXYRIBOSE IF DNA IS TO BE FORMED
o MATURATION OF RBC
o PREVENTS TRAPPING OF FOLIC ACID IN ITS METHYL FORM
Hanggat ang methyl ay nakadikit sa folic acid, hindi sya pwede gumawa ng iba pang form ng
folic acid

Manifestation of vitamin B12 deficiency:

o PERNICIOUS ANEMIA
Macrocytic megaloblastic anemia
With NEUROLOGICAL SYMPTOMS (with degenerative lesions)

Causes of vitamin B12 deficiency:

o REMOVAL OF STOMACH DUE TO LACK OF INTRINSIC FACTOR
o REMOVAL OF LARGE PART OF SMALL INTESTINES
o INCREASE REQUIREMENT IN PREGNANCY
o CHRONIC DIETARY DEFICIENCY

USED TO TEST FOR LEVELS OF B COMPLEX VITAMINS:

B1: TRANSKETOLASE
B2: GLUTATHIONE REDUCTASE
B3: TRYPTHOPHAN LOAD TEST
B6: AMINO TRANSFERASES
B9: HISTIDINE LOAD TEST

ENERGY RELEASING VITAMINS:

B1, B2, B3, B6
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VITAMIN C
Aka: ascorbic acid
Water soluble
Most easily destroyed
Synthesis via: GLUCURONIC ACID CYCLE
takes place only in ANIMALS
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VITAMINS

enzyme involved: gulonolactone oxidase

product: keto-gulonolactone
catabolism:
o vitamin C oxalic acid
o increase vitamin C = increase oxalate concentration
o oxalate may precipitate to form oxalate stones
o factors that promotes formation of oxalate stones:
INCREASE VITAMIN C
DECREASE VITAMIN B6
o DILUTED URINE may prevent formation of oxalate stones

function:
o COLLAGEN SYNTHESIS
production of: hydroxyproline & hydroxylysine
importance of this formation: provides tensile strength of collagen
decrease in vitamin C can cause: rupture of blood vessels
o IRON ABSORPTION
Importance: converts ferric to ferrous
decrease in vitamin C can cause: iron deficiency anemia (nagiging sluggish and sleepy)
o ACTIVATION OF FOLIC ACID TO THFA
decrease vitamin C can cause: macrocytic anemia
o HYDROXYLATION OF CHOLESTEROL TO CHOLIC ACID
Importance: conversion of cholesterol to cholic acid
decrease vitamin C can cause: atherosclerosis
o ANTI-CANCER VITAMIN
Importance: prevents formation of nitrosamine (food coloring)
Decrease vitamin C can cause: carcinogenesis
o ENHANCES IMMUNE SYSTEM

Disease association with deficiency of vitamin C: SCURVY

o bleedinng gums and falling teeth
o Poor wound healing
o Inability to combat infection
o Impaired bone growth
o Roughening of skin
o Scorbutic rosary
swollen costochondrial junction
vitamin C deficiency only
if vitamin D is deficient it is called rachitic
rosary
RDA:
o 1000mg
o The higher the fat & protein content = the higher the vitamin C requirement