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 -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
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)
MANTERANDGATZ 2 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
o
Infantile beri-beri APHONIC TYPE o Manifests laryngeal paralysis PSUDOMENINGITIC TYPE o Convulsive seizures without fever CARDIALGIC TYPE o Baby manifests cyanosis
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
MANTERANDGATZ 3 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)
3D’s of pellagra:
MANTERANDGATZ 4 VITAMINS DERMATITIS Found only in: skin exposed to sun (except: FACE) Manifestation: Cassal’s necklace Gloves and stocking’s 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 o
BLACK TONGUE o This is seen in the tongue of animals that are deficient to niacin
Diseases with pellagra despite of adequate tryptophan: o HARTNUP’S 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
MANTERANDGATZ 5 VITAMINS o
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 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
MANTERANDGATZ 6 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 RBC’s 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
MANTERANDGATZ 7 VITAMINS o o o o
Aka: “double bladed drug” Folic acid antagonist Inhibits: dihydrofolate reductase 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: 5’DEOXYADENOSYLCOBALAMINE (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 o o o o
USED
of vitamin B12 deficiency: REMOVAL OF STOMACH DUE TO LACK OF INTRINSIC FACTOR REMOVAL OF LARGE PART OF SMALL INTESTINES INCREASE REQUIREMENT IN PREGNANCY CHRONIC DIETARY DEFICIENCY
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 -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
VITAMIN C
Aka: “ascorbic acid” Water soluble Most easily destroyed Synthesis via: GLUCURONIC ACID CYCLE takes place only in ANIMALS
MANTERANDGATZ 8 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