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MARI-ANN BENIGNO-BRINGAS, MD Assistant Professor Department of Biochemistry and Nutrition FEU-NRMF Institute of Medicine VITAMINS: Chemistry and Beyond

Vitamins: Biochemistry FEU-NRMF

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Page 1: Vitamins:  Biochemistry FEU-NRMF

MARI-ANN BENIGNO-BRINGAS, MD

Assistant Professor

Department of Biochemistry and Nutrition

FEU-NRMF Institute of Medicine

VITAMINS:Chemistry and Beyond

Page 2: Vitamins:  Biochemistry FEU-NRMF

VITAMINSDefinition I Function

Chemically unrelated organic

nutrients

Classified by their biological and

chemical activity and not by their

structure

Cannot be synthesized in

sufficient quantities

In natural food

Used in many chemical

reactions in the body

Unlike organic food, they do not enter into tissue

structures nor are they converted to

energy

Unlike hormones which are

endogenous, they are exogenous

Page 3: Vitamins:  Biochemistry FEU-NRMF

VITAMINSDefinition I Function

• What vitamins are not:

– Pep pills

– Substitute for carbohydrate, fats and proteins

– Not components of cell structures

Vitamins are diverse but act similar with hormones in regulating cellular metabolism

Page 4: Vitamins:  Biochemistry FEU-NRMF

VITAMINSCLASSIFICATION

Page 5: Vitamins:  Biochemistry FEU-NRMF

VITAMINSDefinition I Function

Characteristics FAT-SOLUBLE VITAMINS WATER-SOLUBLE VITAMINS

Polarity

Absorption

Storage

Transport

Deficiency- prone or not

Toxicity- prone or not

Excretion

Page 6: Vitamins:  Biochemistry FEU-NRMF

VITAMINSDefinition I Function

FAT-SOLUBLE VITAMINS WATER-SOLUBLE VITAMINS

Apolar or hydrophobic Polar

Require normal fat absorption Does not require normal fat absorption

Stored in the liver or adipose tissue No stable storage form (except vitamin B-12)

Transported in the blood by lipoproteins or specific binding proteins

Does not need protein transporters

Less prone to deficiency More prone to deficiency manifestations

Prone to toxicity Less prone to toxicity

Excreted thru feces Excreted mainly thru urine

Page 7: Vitamins:  Biochemistry FEU-NRMF
Page 8: Vitamins:  Biochemistry FEU-NRMF

THIAMINE B1Chemistry

Page 9: Vitamins:  Biochemistry FEU-NRMF

THIAMINE B1Chemistry

• Methylated pyrimidine ring bonded thru a methylene linkage to a thiazole ring

Page 10: Vitamins:  Biochemistry FEU-NRMF

THIAMINE B1Definition

• Anti-neuritic vitamin

• Anti-beriberi vitamin

• Anuerin

• Co-enzyme form:– Thiamine pyrophosphate (TPP)

– Thiamine co-carboxylase

– Thiamine diphosphate

Page 11: Vitamins:  Biochemistry FEU-NRMF

THIAMINE B1Definition

http://www.slideshare.net/namarta28/thiamine

Page 12: Vitamins:  Biochemistry FEU-NRMF

THIAMINE B1Properties

Page 13: Vitamins:  Biochemistry FEU-NRMF

THIAMINE B1Metabolic Role

• Energy-releasing

• Has a central role in carbohydrate metabolism

• Half-life is 9-18 days• Sources:

– Meat/fish

– Beans, Nuts, Yeast

– What flour, unpolished rice

– Liver, meat, eggs

Page 14: Vitamins:  Biochemistry FEU-NRMF

THIAMINE B1Metabolic Roles

• Co-enzyme in the decarboxylation of:

PyruvateAlpha-

ketoglutarate

Keto acids from branch-chain amino acids

Page 15: Vitamins:  Biochemistry FEU-NRMF

THIAMINE B1Metabolic Roles

• Co-enzyme in the transketolase reactions

– RBC transketolase in most commonly used in measuring thaimine status in the body

Page 16: Vitamins:  Biochemistry FEU-NRMF

THIAMINE B1Metabolic Roles

• Thiamine triphosphate (TTP)

nerve tissue metabolism and

conduction

Synthesis of neurotransmitters

(Ach)

Regulates nerve-impulse

transmission

Page 17: Vitamins:  Biochemistry FEU-NRMF

THIAMINE B1Metabolic Roles

Central role of thiamine diphosphate

w

Page 18: Vitamins:  Biochemistry FEU-NRMF

THIAMINE B1Metabolic Roles

Page 19: Vitamins:  Biochemistry FEU-NRMF

THIAMINE B1Metabolic Roles

Page 22: Vitamins:  Biochemistry FEU-NRMF

TPP

TPP

Page 23: Vitamins:  Biochemistry FEU-NRMF

THIAMINE B1Deficiency

May occur in the following conditions:

When the energy intake is mostly from

rice

Ingestion of foods containing anti-

thiamine factors.

Pregnancy and Lactation

Persons who do hard physical labor

Page 24: Vitamins:  Biochemistry FEU-NRMF

THIAMINE B1Deficiency

4 Types of Beriberi

Dry

(peripheral neuritis)

Wet (cardiac manifestations)

Cerebral

(Wernicke-Korsakoffsyndrome)

Infantile

Page 25: Vitamins:  Biochemistry FEU-NRMF

THIAMINE B1Deficiency

Dry Beriberi

Loss of appetite

Weight loss

Muscle-wasting

Peripheral neuritis with numbness

Tingling sensations in the lower legs and feet

Ataxic gait

Page 26: Vitamins:  Biochemistry FEU-NRMF
Page 27: Vitamins:  Biochemistry FEU-NRMF

THIAMINE B1Deficiency

Wet Beriberi

Vasodilatation, tachycardia, wide pulse pressure, sweating , warm skin

lactic acidosis

Heart Failure

Orthopnea Pulmonary and peripheral edema

Vaasodilatation

Shock

Page 28: Vitamins:  Biochemistry FEU-NRMF
Page 29: Vitamins:  Biochemistry FEU-NRMF

THIAMINE B1Deficiency

Cerebral Beriberi

Occurs in alcoholics who consume less food

Intelligence disturbance

Ataxia

Double vision

Nystagmus

Progresses to Wernicke-Korsakoff psychosis

Page 30: Vitamins:  Biochemistry FEU-NRMF

THIAMINE B1Deficiency

Soshin Beriberi

More rapid form of wet beriberi

Acute fulminant CV beriberi

Cyanosis of hands and feet, tachycardia, distended neck veins, anxiety

Rapid deterioration follows inability of heart muscle to satisfy body’s demands because of its own injury

Page 31: Vitamins:  Biochemistry FEU-NRMF

THIAMINE B1Deficiency

Page 32: Vitamins:  Biochemistry FEU-NRMF

THIAMINE B1Deficiency

Infantile Beriberi

Due to low thiamine content of breast milk

Anorexia

Trachycardia

Vomiting

Convulsions

Edema

Page 33: Vitamins:  Biochemistry FEU-NRMF

THIAMINE B1Deficiency

Beriberi

TYPE OF BERIBERI COMMON SYMPTOMS/FINDINGS

Neuropsychiatric Hallucinations, aggressive behavior, confusion, nystagmus, ataxia, ophthalmoplegia

Dry - Neurologic Numbness, muscle weakness, pain in the lower > uppper extremities (stocking-glove distribution) convulsions, exaggerated tendon reflexes

Wet - High output CVD Tachycardia, respiratory distress, leg edema, right ventricular dilation, lactic acidosis

Gastrointestinal Nausea, emesis, megajejunum, constipation, megacolon, atony

Source: Medscape Nat Rev Gastorenerol hepatol 2010 nature Publishing

Page 34: Vitamins:  Biochemistry FEU-NRMF

RIBOFLAVIN B2Definition I Function

• Synonyms :

– Vitamin B2, Vitamin G, Lactoflavin

• Chemistry:– Consists of heterocyclic isoalloxazine ring attached

to a sugar alcohol, robitol

Page 35: Vitamins:  Biochemistry FEU-NRMF

RIBOFLAVIN B2Definition I Function

• Co-enzyme forms:

– FMN Flavin mononucleotide

– FAD Flavin adenine dinucleotide

Page 36: Vitamins:  Biochemistry FEU-NRMF

RIBOFLAVIN B2Properties

• Colored, flourescent pigment

• Widely used as food additive

• Heat stable but decomposes in the presence of visible light

Page 37: Vitamins:  Biochemistry FEU-NRMF

RIBOFLAVIN B2Definition I Function

• RDA :

– Adults: 2.0 mg/day

– Children: 1.2 mg/day

– Pregnant/lactating: 2.0 mg/day

• Sources:

– Milk - 1 quart = 1.7 mg

Page 38: Vitamins:  Biochemistry FEU-NRMF

RIBOFLAVIN B2Physiologic Roles

• Act as prosthetic group of flavoproteins

• Act as co-enzyme for hydrogen transfer

Page 39: Vitamins:  Biochemistry FEU-NRMF

RIBOFLAVIN B2Metabolic Roles

• Flavoproteins:

– Enzymes involved in oxidation – reduction reactions

– FAD is required as coenzyme for:

Pyruvate dehydrogenase Carbohydrate breakdown

Succinate dehydrogenase Krebs cycle

Glycerol 3-phosphate dehydrogenase

Triglyceride synthesisphospholipid synthesis

Acyl-CoA dehydrogenase Fatty acid breakdown

Glutathione reductase Anti-oxidation

Page 40: Vitamins:  Biochemistry FEU-NRMF

RIBOFLAVIN B2Metabolic Roles

• Flavoproteins:

– Enzymes involved in oxidation – reduction reactions

– FMN is required for:

• L-amino acid oxidase

• Cytochrome C reductase

Page 41: Vitamins:  Biochemistry FEU-NRMF

REACTIONS WHERE FAD IS NEEDED AS COENZYME

Substrate Enzyme Product

Hypoxanthine + O2 + H2O Xanthine Oxidase Xanthine + H2O2

Xanthine + O2 + H2O Xanthine Oxidase Urate + H2O2

Succinate Succinate DH Fumarate

Glycerophosphate Glycerophosphate DH Dihydroxyacetone-PO4

Flavoproteins in electron transport chain

Glutathione reductase – for assaying riboflavin status

Part of pyruvate dehydrogenase and alpha-ketoglutaratedehydrogenase complexes

RIBOFLAVIN B2Metabolic Roles

Page 42: Vitamins:  Biochemistry FEU-NRMF

FAD

FAD

FAD

FAD

Page 43: Vitamins:  Biochemistry FEU-NRMF

• Causes:– Malnutrition

– Malabsorption

– Anorexia

– Chronic alcoholism

• Assay for Riboflavin status:

– Erythrocyte GSH reductase activity

RIBOFLAVIN B2Deficiency

Page 44: Vitamins:  Biochemistry FEU-NRMF

• Ariboflavinosis

• Manifestations:

– Epithelial changes in the oral cavity• Cheilosis or perleche – fissuring of lips

• Glossitis- Magenta tongue

– Corneal Vascularization

– Seborrheic Dermatitis

– Photophobia

RIBOFLAVIN B2Deficiency

Page 45: Vitamins:  Biochemistry FEU-NRMF

• Angular stomatitis

• A

RIBOFLAVIN B2Deficiency

Page 46: Vitamins:  Biochemistry FEU-NRMF

• Glossitis

RIBOFLAVIN B2Deficiency

Page 47: Vitamins:  Biochemistry FEU-NRMF

NIACIN B3Definition I Function

• Not strictly a vitamin

• SYNONYMS

– Vitamin B3, Nicotinic acid, PP factor

– Nicotinamide, niacinamide

• CO-ENZYME FORMS

– Oxidized = NAD and NADP

– Reduced= NADH AND NADPH

Page 49: Vitamins:  Biochemistry FEU-NRMF

NIACIN B3Definition I Function

• RDA:

– Adults: 16-20 mg/day

– Children: 9-16 mg/day

– Infants: 5-8 mg/day

Page 50: Vitamins:  Biochemistry FEU-NRMF

NIACIN B3Coenzymes

Page 51: Vitamins:  Biochemistry FEU-NRMF

NIACIN B3Coenzymes

Page 52: Vitamins:  Biochemistry FEU-NRMF

Examples of Reactions Utilizing NAD and NADP

Substrate Enzyme Product

Lactate Lactate DH

Pyruvate

MalateMalate DH

Oxaloacetate

HydroxybutyrateBeta-OH- butyrate DH

Acetoacetate

GlucoseGlucose DH

Gluconate

IsocitrateIsocitrate DH

Alpha-ketoglutarate

GlutamateGlutamate DH

Alpha-ketoglutarate + Ammonia

Page 53: Vitamins:  Biochemistry FEU-NRMF

NAD

NAD

NAD

NAD

NAD

NAD

NADNAD

NAD

Page 54: Vitamins:  Biochemistry FEU-NRMF

NIACIN B3Deficiency

• CLINICAL EFFECTS:

Pellagra “rough skin” – 3D’s– Dermatitis –skin exposed to sunlight

• Casal’s necklace

• Gloves and stockings lesions

– Diarrhea

– Dementia

– Stomatitis, magenta tongue

– Severe cases, GIT hemorrhagic

* ineffective repair and regeneration of epithelial cells

Page 55: Vitamins:  Biochemistry FEU-NRMF

NIACIN B3Deficiency

Dermatitis of Pellagra

Casal’s Necklace

Page 56: Vitamins:  Biochemistry FEU-NRMF

NIACIN B3Deficiency

Dermatitis of Pellagra

Gloves and stocking appearance

Page 57: Vitamins:  Biochemistry FEU-NRMF

NIACIN B3Excess

Toxicity

• 1-6 grams ( hyperlipidemia)

• Dilatation of blood vessels

• Flushing

• Skin irritation

• Liver damage

Page 58: Vitamins:  Biochemistry FEU-NRMF

PYRIDOXINE B6Definition I Function

• FUNCTION

– Precursor of pyridoxal phosphate

– Coenzyme for several enzymes for AMINO ACID METABOLISM

• DEFICIENCY

– Intake of Isoniazid

Page 59: Vitamins:  Biochemistry FEU-NRMF

PYRIDOXINE B6Definition I Function

• SYNONYMS:– Amino acid metabolism vitamin

– Rat anti-dermatitis factor

– Adermin

– Rat anti-pellagra factor

– Vitamin H

– Rat acrodyna factor

• CO-ENZYME FORMS:

– Pyridoxal phosphate and pyridoxinaminephosphate

– Major excretory product: 4-Pyridoxic acid

Page 60: Vitamins:  Biochemistry FEU-NRMF

PYRIDOXINE B6Definition I Function

• Sources:– Whole grain & legumes

– Poultry & Fish

– Potatoes

– Organ meats

– Eggs

• RDA:– Adults: 2.2 mg/day

– Children: 1.2 mg/day

– Infants: 3.0 mg/day

Page 61: Vitamins:  Biochemistry FEU-NRMF

PYRIDOXINE B6Food Sources

• RDA: Roughly proportional to the protein content of the diet

– 0.02 mg/g of protein intake

– 1.5-2.0 mg/day for normal adult

– Increased during pregnancy and lactation

Page 62: Vitamins:  Biochemistry FEU-NRMF

PYRIDOXINE B6Definition I Function

Page 63: Vitamins:  Biochemistry FEU-NRMF

PYRIDOXINE B6Definition I Function

Page 64: Vitamins:  Biochemistry FEU-NRMF

PYRIDOXINE B6Definition I Function

• Physiological importance:

– Amino acid metabolism

– Synthesis of ceramide

– Synthesis of the neurotransmitters

serotonin, dopamine, epinephrine,

norepinephrine & GABA.

– Synthesis of the histamine.

– Synthesis of porphyrins

– Glycogenolysis - phosphorylase

Page 65: Vitamins:  Biochemistry FEU-NRMF

PYRIDOXINE B6Definition I Function

• Co-enzyme in protein metabolism– Decarboxylation

– Conversion of 3-hydroxykynurenine to 3-OH-anthranilic acid

– Conversion of Tryptophan to serotonin

– Deamination – serine and threonine

– Transamination – acts as an amino group carrier

Page 66: Vitamins:  Biochemistry FEU-NRMF

PYRIDOXINE B6Definition I Function

Page 67: Vitamins:  Biochemistry FEU-NRMF

PYRIDOXINE B6Definition I Function

• Co-enzyme in protein metabolism– Trans-sulfuration

• transfer of sulfur from methionine to serine to form cysteine

– Conversion of cysteine to pyruvate

• via cysteine desulfhydrase

– Interconversion of glycine and serine

– Decarboxylation of alpha-amino-beta-ketoadipic acid to delta-aminolevulinic acid

Page 68: Vitamins:  Biochemistry FEU-NRMF

PYRIDOXINE B6Definition I Function

• Co-enzyme in carbohydrate and fat metabolism

– Conversion of Linoleic to Arachidonic acid

– Cofactor in the activity of phosphorylase

– Cofactor in the metabolism of unsaturated fatty acids and cholesterol

– Synthesis of sphingolipids necessary for myelin formation

Page 69: Vitamins:  Biochemistry FEU-NRMF

PYRIDOXINE B6Definition I Function

• Enzymes :

Amino transferases amino acid breakdown

Glycogen phosphorylase glycogen breakdown

Serine dehydratase feeding serine's breakdown product to gluconeogenesis

Aminolevulinic acid synthase

porphyrin synthesis

Page 70: Vitamins:  Biochemistry FEU-NRMF

PYRIDOXINE B6Definition I Function

• Essential for the maintenance of the integrity of :

– Neuronal tissues

– Production of anti-bodies

– Bone development

Page 71: Vitamins:  Biochemistry FEU-NRMF

PLP

PLP

PLP

PLP

Page 72: Vitamins:  Biochemistry FEU-NRMF

PYRIDOXINE B6Deficiency

• Clinical features:

– Epileptiform seizures in infants

– Pellagra-like skin lesions

– GIT involvement- distention, vomiting , diarrhea

– Anemia- hypochromic and microcytic

– Acrodynia – in rats

Page 73: Vitamins:  Biochemistry FEU-NRMF

PYRIDOXINE B6Biochemistry

• Important biochemical finding in Vitamin B6 deficiency:– Increased excretion of urinary oxalates

– Mechanism:

decreased conversion of glycine glyoxalate broken down to oxalic acid increased possibility of forming oxalate stones

• Most widely used assessment method: – Activation of erythrocyte aminotransferases by pyridoxal phosphate

added invitro, expressed as activation coefficient.

Page 75: Vitamins:  Biochemistry FEU-NRMF

PANTOTHENIC ACIDFunction

• FUNCTION

– Component of Coenzyme A

• RDA:

– Adults: 5-10 mg/day

– Children: 4-5 mg/day

– Infants: 1-2 mg/day

Page 76: Vitamins:  Biochemistry FEU-NRMF

PANTOTHENIC ACIDFunction

Substrate Enzyme Product

Pyruvate + CoASHPyruvate DH complex

Acetyl CoA

α-ketoglutarate- CoASHAlpha-KG DH complex

Succinyl CoA

Fattyl acid + CoASHThiokinase

Acetyl-CoA

Ketoacyl CoA + CoASHThiolase

Acyl CoA + Acetyl CoA

Detoxification of benzoic acid

Synthesis of bile salts

Page 77: Vitamins:  Biochemistry FEU-NRMF

PANTOTHENIC ACIDFunction

• As Acetyl CoA

Combines with oxaloacetic acid to form citric acid –

first step in the Kreb’s cycle

Combines with choline to form acetylcholine

Combines with sulfonamide drugs to facilitate their

excretion

Precursor of cholesterol / steroid

hormones

Activation of some amino acids :

valine, leucine and isoleucine

Essential function in lipid metabolism

Page 78: Vitamins:  Biochemistry FEU-NRMF

PANTOTHENIC ACIDFunction

• As Succiny CoA

– Involved in heme biosynthesis

• As Acyl Carrier Protein

– Involved in fatty acid biosynthesis

– Extra-mitochondrial lipogenesis

Page 79: Vitamins:  Biochemistry FEU-NRMF

Acetyl CoA

Page 80: Vitamins:  Biochemistry FEU-NRMF

PANTOTHENIC ACIDDeficiency

• Rare because:– Very widespread in natural foods

– Most symptoms are vague and mimic those of other B vitamin deficiencies

Page 81: Vitamins:  Biochemistry FEU-NRMF

BIOTIN B7Definition

• SYNONYMS:

– Vitamin B7; anti-egg white injury factor

• CHARACTERISTICS:

– Widely distributed in natural foods

– From synthesis of bacteria - deficiency is caused by defects in utilization and not dietary

– Long-term antibiotic treatment or excessive consumption of raw egg

Page 82: Vitamins:  Biochemistry FEU-NRMF

BIOTIN B7Definition

• AVIDIN – a protein in raw egg white which combines very tightly with biotin, preventing its absorption

Page 83: Vitamins:  Biochemistry FEU-NRMF

BIOTIN B7Function

• FUNCTION

– Coenzymes for carboxylation reactions

– Carrier of activated carbon dioxide

• FOOD SOURCES

– Almost all foods, liver, milk, egg yolk

– 400 µg/day

• DEFICIENCY

– Uncommon

– Raw egg avidin prevents absorption of Biotin

Page 84: Vitamins:  Biochemistry FEU-NRMF

BIOTIN B7

Page 85: Vitamins:  Biochemistry FEU-NRMF

CARBOXYLATION REACTIONS:

BIOTIN B7Function

Substrate Enzyme Product

Acetyl CoAacetyl CoA

carboxylase

Malonyl CoA

Propionyl CoAPropionyl CoAcarboxylase

MethylmalonylCoA

Pyruvatepyruvate

carboxylase

Oxaloacetic acid

Page 86: Vitamins:  Biochemistry FEU-NRMF

Biotin

Biotin

Page 87: Vitamins:  Biochemistry FEU-NRMF

• Man (rare)– Fine scaly skin desquamation

– Anorexia

– Nausea

– Lassitude

– Muscle pains

– Depression/hallucination

– Alopecia

– Graying of hair

BIOTIN B7Deficiency

Page 88: Vitamins:  Biochemistry FEU-NRMF

BIOTIN B7Deficiency

In rats

- “spectacle-eyed” appearance

- “Kangaroo posture”

- retarded growth

- loss of hair

- loss of muscular control

Page 89: Vitamins:  Biochemistry FEU-NRMF

FOLIC ACID B9Facts

• SYNONYMS:

– Vit B9, Folate, Folacin, PGA (Pteroylglutamic acid)• FUNCTION

– One-Carbon metabolism– Essential in biosynthesis of thymidine, AA, and

purine

Page 90: Vitamins:  Biochemistry FEU-NRMF

FOLIC ACID B9Facts

• FOOD SOURCES– Green leafy vegetables, liver, lima beans, whole

grain cereals• DEFICIENCY

– Growth failure – Megaloblastic anemia– Neural tube defects

Page 91: Vitamins:  Biochemistry FEU-NRMF

FOLIC ACID B9Structure

Page 92: Vitamins:  Biochemistry FEU-NRMF

FOLIC ACID B9Structure

For transfer and utilization of the single carbon moiety.

Page 93: Vitamins:  Biochemistry FEU-NRMF

FOLIC ACID B9Functions

– Carrier of one-carbon group moieties.

Form Formula Name

Most reduced CH3 Methyl

Intermediate CH2 Methylene

Most oxidized CHO Formyl

CHNH Formimino

CH= methenyl

Page 94: Vitamins:  Biochemistry FEU-NRMF

FOLIC ACID B9Forms

Form Decription

N5-methyl- THFA Most prevalent form transported in the blood

N5, N10-methylene THFA Provides methyl group in the formation of thymidylate for DNA synthesis and erythrocyte formation

N10 formy; THFA Provides C atom that becomes C2 of purinenucleus

N5-formimino THFA Histidine catabolism

N10-hydroyxymethyl THFA Thymine synthesis

Page 95: Vitamins:  Biochemistry FEU-NRMF

FOLIC ACID B9Function

Page 96: Vitamins:  Biochemistry FEU-NRMF

FOLIC ACID B9Function

400 ug folate supplement

Page 97: Vitamins:  Biochemistry FEU-NRMF

FOLIC ACID B9Deficiency

Blood Cell Macrocytic Anemia- impaired production

Blood Cell Microcytic Anemia

Results when RBC are unable

to divide…

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Page 99: Vitamins:  Biochemistry FEU-NRMF

THFA

THFATHFA

Page 100: Vitamins:  Biochemistry FEU-NRMF

VITAMIN B12Definition

• SYNONYMS:

– Antipernicious anemia vitamin

– Cobalamin

– Extrinsic Factor of Castle

– Erythrocyte Maturation Factor

• CHEMISTRY:

Page 101: Vitamins:  Biochemistry FEU-NRMF

VITAMIN B12Chemistry

• Consists of:

1. Corrin ring system - central portion of the molecule: similar to a porphyrin ring

2. 5,6-dimethylbenzimidazole riboside

3. Aminopropanolol

4. Propionic acid

5. Cobalt-occupies the center of the corrin ring system

1

5

43

2

Page 102: Vitamins:  Biochemistry FEU-NRMF

VITAMIN B12Function

• FUNCTION– Synthesis of methionine

– Isomerization of methylmalonyl CoA

Page 103: Vitamins:  Biochemistry FEU-NRMF

VITAMIN B12Function

– Involved in the rearrangement of methylmalonyl CoA to succinyl CoA by methylmalonyl CoA isomerase

• Involved in the transfer of a methyl group from methylTHFA to homocysteine to form methionine .

Page 104: Vitamins:  Biochemistry FEU-NRMF

B-12

B-12B-12

Page 105: Vitamins:  Biochemistry FEU-NRMF

VITAMIN B12Sources І Deficiency

• FOOD SOURCES– Synthesized by microorganisms in the bacterial flora

– Liver, whole milk, eggs

– oysters, fresh shrimp, pork, chicken

• RDA– Children: 2ug/day

– Adults 3 ug/day

– Pregnancy and lactation: 4 ug/day

• DEFICIENCY– Abnormal fatty acid synthesis

– Cell membrane defects/Neurological abnormalities

– Pernicious anemia

Page 106: Vitamins:  Biochemistry FEU-NRMF

VITAMIN B12Forms

Forms Content

Cobalamin Without cyanide

Cyanocobalamin with cyanide group

Hydroxocobalamin with hydroxyl group, more active in enzyme systems; retained longer in the body

Methylcobalamin major form in the plasma

5’-deoxyadenosylcobalamin

readily binds to plasma-binding proteins

Page 107: Vitamins:  Biochemistry FEU-NRMF

VITAMIN B12Deficiency

• Causes:

– Chronic dietary deficiency of vitamin B-12.

– Poor absorption due to lack of intrinsic factor.• Presence of antibodies to the intrinsic factor in the gastric

juice.

• Lack of secretion of intrinsic factor (due to gastric mucosal cell atrophy or due to total gastrectomy.

• Extensive resection of the small intestines.

– Increased requirements as in pregnancy.

Page 108: Vitamins:  Biochemistry FEU-NRMF

VITAMIN B12Deficiency

• Clinical effects: “Pernicious Anemia”

• No healthy RBC

• Characterized by:

– Megaloblastic or macrocytic anemia.

– Lesions of the nervous system

– Mucosal atrophy and inflammation of the tongue (glossitis), mouth (stomatitis) and pharynx (pharyngitis)

Page 110: Vitamins:  Biochemistry FEU-NRMF
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ASCORBIC ACID Facts

• Anti-scorbutic vitamin

• Very sensitive to oxidation

• Rapidly destroyed by alkalies

• Freezing has no deleterious effect

• Strong reducing agent

• Drying vegetables usually results in loss of vitamin C.

• Pasteurizing milk destroys vitamin C

Page 112: Vitamins:  Biochemistry FEU-NRMF

ASCORBIC ACID Facts

• Sources:

– Citrus fruits

– Tomatoes

– Strawberries

– Green vegetables

– Guava fruit

– Green pepper

• RDA:

– Adults: 60 mg/day

– Children: 40 mg/day

Page 114: Vitamins:  Biochemistry FEU-NRMF

ASCORBIC ACID Facts

Page 115: Vitamins:  Biochemistry FEU-NRMF

ASCORBIC ACID Metabolic roles

Hydroxylation of Proline and

Lysine in collagen formation.

Hydroxylation of tryptophan Synthesis of

norephinephrine

Tyrosine metabolism

Hydroxylation of steroids in the adrenal cortex

Serves as a reductant of

ferric to ferrous ion

Involved in the conversion of folic acid to active THFA

Involved in the hydroxylation of cholesterol to

cholic acid

Acts as regulator of cholesterolmetabolism

Page 116: Vitamins:  Biochemistry FEU-NRMF

ASCORBIC ACID Function

• Major function of vitamin C– coenzyme in the formation of tissue collagen or intracellular cement

substance

Page 117: Vitamins:  Biochemistry FEU-NRMF

ASCORBIC ACID Function

• Major function of vitamin C– coenzyme in the formation of tissue collagen or intracellular cement

substance

Page 118: Vitamins:  Biochemistry FEU-NRMF

ASCORBIC ACID Deficiency

• Spongy gums

• Poor wound healing

Page 119: Vitamins:  Biochemistry FEU-NRMF

ASCORBIC ACID Deficiency

• Splinter hemorrhages in nails

• Petechial, subcutaneous hemorrhages

Page 120: Vitamins:  Biochemistry FEU-NRMF

ASCORBIC ACID Deficiency

• Scorbutic rosary beads -swelling at the ends of long bones

Page 121: Vitamins:  Biochemistry FEU-NRMF

FAT-SOLUBLE VITAMINSStructure

• Vitamin A retinol, B-carotenes

• Vitamin D cholecalciferol

• Vitamin K phylloquinones, menaquinones

• Vitamin E tocopherols

Page 122: Vitamins:  Biochemistry FEU-NRMF

VITAMIN A RetinolStructure

Β-carotene dioxygenase + bile Acids

Retinaldehyde reductase + NADH, NADPH

Page 123: Vitamins:  Biochemistry FEU-NRMF

VITAMIN A RetinolStructure

• Retinol and retinoic acid – act like steroid hormones

• Retinalehyde is a component of Rhodposin

• Retinoic acid participates in glycoprotein synthesis

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VITAMIN A RetinolFunction

• Provitamin - β carotene

• FUNCTION– Maintenance of reproduction

– Maintenance of vision

– Promotion of growth

– Gene expression

– Treatment of psoriasis, acne, cancers

• FOOD SOURCES– Liver, kidney, cream, butter, egg yolk

– Yellow and dark green vegetables

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VITAMIN A RetinolFunction

RAR and RXR form RAR/RXR heterodimers, which bind to regulatory regions of the chromosome called retinoic acid response elements (RARE). Binding of all-trans-RA and 9-cis-RA to RAR and RXR respectively allows the complex to regulate the rate of gene transcription.

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ACTION OF RETINOIDS

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VITAMIN D Facts

• FUNCTION

– 1,25-dihydrocholecalciferol- a steroid hormone

– Stimulates gene expression or repress gene transcription

– Regulates plasma levels of calcium and phosphorus

• FOOD SOURCES

– Liver, kidney, fatty fish, egg yolk

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VITAMIN D Action

Response to low

plasma calcium

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VITAMIN D Action

Response to low

plasma calcium

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VITAMIN D Deficiency

• DEFICIENCY– Rickets

– Osteomalacia(demineralization of bone)

• TOXICITY– Most toxic of all vitamins

– Deposition of calcium in organs and arteries, kidney stones

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VITAMIN K Function

• FUNCTION

– Post-translational modification of various blood clotting factors

– Phylloquinone (plants)

– Menaquinone (intestinal bacterial flora)

– Menadione

• FOOD SOURCES

– Cabbage, cauliflower, spinach, egg yolk, liver

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VITAMIN K Function

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VITAMIN K Function

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VITAMIN K Warfarin is a vitamin K antagonist that inhibits the recycling of vitamin K at two dithiol-dependent steps.

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VITAMIN E Function

• FUNCTION– -tocopherol

– Anti-oxidant

• FOOD SOURCES– Vegetable oils, liver, eggs

• DEFICIENCY– Heart disease

– Defective cell membranes

– Cataract formation

• TOXICITY– No toxicity at 300 mg/day

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VITAMINSDefinition I Function

VITAMIN FUNCTIONS DEFICIENCY DISEASE

A Retinol, β-carotene

Visual pigments in the retina; regulation of gene expression and cell differentiation;Antioxidant

Night blindness, xerophthalmia;keratinization of skin

D Calciferol Maintenance of calcium balance; enhances intestinal absorption of Ca++ and mobilized biomineral

Rickets = poor mineralization of bones;Osteomalacia = bone demineralization

E TocopherolsTocotrienols

Antioxidant, especially in cell membranes

Extremely rare - serious neurologic dysfunction

K PhylloquinoneMenaquinone

Coenzyme in formation of γ-carboxyglutamate in enzymes of blood clotting and bone matrix

Impaired blood clotting, hemorrhagic disease

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VITAMINSDefinition I Function

VITAMIN FUNCTIONS DEFICIENCY DISEASE

B1 Thiamin Coenzyme in pyruvate and α-ketoglutarate DH, and transketolase; poorly defined function in nerve conduction

Peripheral nerve damage (beriberi) or CNS lesions (Wernicke-Korsakoffsyndrome)

B2 Riboflavin Coenzyme in redox reactions; prosthetic group of flavoproteins

Lesions of corner of mouth, lips and tongue,seborrheic dermatitis

B3 Niacin Nicotinic acidNicotinamide

Coenzyme in redox reactions; functional part of NAD and NADP

Pellagra- photosensitivedermatitis, depressive psychosis

Energy-Releasing

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VITAMINSDefinition I Function

Energy-Releasing

VITAMIN FUNCTIONS DEFICIENCY DISEASE

Pantothenic Acid Functional part of CoA and acylcarrier protein: fatty acid synthesis and metabolism

H Biotin Coenzyme in carboxylationreactions in gluconeogenesisand fatty acid synthesis

Impaired fat and CHO metabolism, dermatitis

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VITAMINSDefinition I Function

VITAMIN FUNCTIONS DEFICIENCY DISEASE

Folic acid Coenzyme in transfer of one-carbon fragments

Megaloblastic anemia

B12 Cobalamin Coenzyme in transfer of one-carbon fragments and metabolism of folic acid

Pernicious anemia = megaloblastic anemiawith degeneration of the spinal cord

Hematopoeitic

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VITAMINSDefinition I Function

VITAMIN FUNCTIONS DEFICIENCY DISEASE

B6 PyridoxinePyridoxalPyridoxamine

Coenzyme in transamination & decarboxylation of AA and glycogen phosphorylase; role in steroid hormone action

Disorders of AA metabolism, convulsions

C Ascorbic Acid Coenzyme in hydroxylation of proline and lysine in collagen synthesis; antioxidant; enhances iron absorption

Scurvy- impaired wound healing, loss of dental cement, subcutaneous hemorrhage

Other functions

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VITAMINSDefinition I Function

• w

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