VITAMINS and COFACTORS

WATER-SOLUBLE VITAMINS• B1• B2• B6• B12• C• Folate• Biotin• Niacin• CoA

• Oxidative decarboxylation of a-keto acids

• Transketolase reaction

B1 -THIAMINE PYROPHOSPHATE

B1 -THIAMINE PYROPHOSPHATEDEFICIENCY (BERIBERI)

EARLIEST SYMPTOMS• Constipation• Appetite suppression• Nausea• Mental depression• Peripheral neuropathy• Fatigue

CHRONIC DEFICIENCY• Severe neurological

symptoms• Ataxia• Mental confusion• Loss of eye coordination• Cardiomegaly• Cardiac failure• Musculature defects

WERNICKE-KORSAKOFF SYNDROME•Amnesia •Encephalopathy

B2 - FLAVIN NUCLEOTIDES

They are derivatives of riboflavin or vitamin B2

• Flavin Mononucleotide (FMN)• Flavin Adenine Dinucleotide (FAD)

Riboflavin (B2)Riboflavin (B2)

FMN - FLAVIN MONONUCLEOTIDE

• FMN• Riboflavin• Dehydrogenation of

two consecutive carbon atoms

• Dehydrogenation of NAD+ in Electron Transport Chain

Riboflavin (B2)FMN

FAD - FLAVIN ADENINE DINUCLEOTIDE

• FAD• Riboflavin• Dehydrogenation

of two consecutive carbon atoms

AriboflavinosisRiboflavin (B2)FMNFAD

B2 - ARIBOFLAVINOSIS•Glossitis•Seborrhea•Angular stomatitis•Cheilosis•Photophobia

•It is rare in USA and other developed countries due to the presence of adequate amounts of the vitamin in the diet.

•It is often seen in chronic alcoholics

•Riboflavin decomposes when exposed to visible light. This characteristic can lead to a deficiency in newborns treated for hyperbilirubinemia by phototherapy.

B6 - PYRIDOXAL AND PYRIDOXAMINE

PHOSPHATEREACTIONS:• Glycogenolysis• METABOLISM OF AMINO ACIDS

RacemizationTransaminationNon-oxidative deamination

DISEASE: • Neuritis• Isoniazid (to rx TB)• Penicillamine

Pyridoxol

Pyridoxal

Pyridoxamine

Pyridoxal Phosphate

Pyridoxamine Phosphate

DISEASE:• Pernicious anemia• Megaloblastic anemia• Nerve demyelinization

B12 - ADENOSYL COBALAMINE

REACTIONS:• Metabolism of one carbon atom fragment• Isomerization of methylmalonyl-CoA

Vitamin B12• Only water-soluble vitamin that can be stored (in

liver), enough for a 3 year supply• Intrinsic factor produced in stomach facilitates

transport from gut to blood• Deficiency of IF (can be autoimmune) can result

in B12 deficiency• Possible to get def. if vegetarian but rare• Elevated urine methylmalonate levels• Rx is B12 injections

• Synthesis of hydroxyproline and hydroxylysine in tropocollagen

• Catabolism of tyrosine, Synthesis of catecholamines (norepinephrine from dopamine)

• Synthesis of steroids• Antioxidant, facilitates absorption of Fe in intestines

VITAMIN C

SCURVY•Easily bruised skin

•Muscle fatigue

•Soft swollen gums

•Decreased wound healing

•Hemorrhaging

•Osteoporosis

•Anemia

THF - TETRAHYDROFOLATE

• Transfer of one carbon atom fragment with different oxidation status

• Very important in the synthesis of nucleotides• DISEASE: Megaloblastic anemia

COFACTORS FROM TETRAHYDROFOLATE

BIOTIN• Biocitin• ATP dependent

carboxylation reactions• Transcarboxylation

DISEASE IS UNCOMMON

•Deficiency of biotinidase•Raw eggs (avidin)•Antibiotics

•Dermatitis•Loss of hair•Paralysis

NIACIN (B3 or PP)

Nicotinic acid Nicotinamide

• NAD+ & NADP+

Hartnup diseaseCarcinoid syndromeIsoniazid

• Oxidation of one carbon atom

PELLAGRA• Glossitis• Dermatitis• Weight loss• Diarrhea• Depression• Dementia

Other Causes of Deficiency

NICOTINAMIDE ADENINE

DINUCLEOTIDE

• NAD+

• Oxidation of one carbon atom

• Feed the Electron Transport Chain

Hey, look at me!!!!

NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE

• NADP+

• Oxidation of one carbon atom

• Most important source of reduction equivalent for synthesis

Hey, look at me!!!!

COENZYME A• Transfer of acyl groups

Pantothenic acid

CoA-SH

• NO DISEASE

FAT-SOLUBLE VITAMINS

• Vitamin A• Vitamin D• Vitamin E• Vitamin K

VITAMIN A

b-Carotene

Retinol All-trans-retinal

11-cis-retinalRetinoic acid

VITAMIN AHormone????? • Interacting with genes:

• growth and differentiation• retinoic acid is involved in the earliest processes of embryogenesis including the differentiation of the three germ layers, organogenesis and limb development.

Abnormal osteogenesis

• Synthesis of glycoproteins and mucopolysaccharides necessary for mucous production and normal growth regulation

Cofactor • Visual pigment

AVITAMINOSIS HYPERVITAMINOSISNight blindness

Follicular hyperkeratinosisSusceptibility to infection

Susceptibility to cancerAnemia

Keratinization of the cornea (xerophthalmia)

Bone pain

Hepatosplenomegaly

Nausea

Diarrhea

VITAMIN E

• Antioxidant agent• Detoxification of free radicals

a-Tocopherol

Vitamin E is a mixture of several related compounds known as tocopherols

Red blood cell fragilityNeurological disordersIncreased risk of certain cancers

DEFICIENCY

VITAMIN K

• Transfer of Hydrogen and electrons• g-carboxylation of glutamate in several blood

clotting factors (II, VII, IX, X)

• DISEASE: Bleeding

Phylloquinone

Cofactors

• Coenzyme Q• Heme• Lipoamide• Adomet• Adocys• Minerals

COENZYME QNO VITAMIN

• Carrier of Hydrogen and electrons in the Electron Transport Chain

• Connector of Complex I and II with Complex III

Ubiquinone

Ubihydroquinone

HEME

HEME AND HEMINE

• CYTOCHROMES• Carrier of electron in

the Electron Transport Chain

• Detoxification of the organism

• CATALASES AND PEROXYDASES

• Detoxification of free radicals

LIPOAMIDE• Oxidative decarboxylation of a-keto acid

Lipoic acid

Dihydrolipoic acid

• Transfer of methyl groups

S-ADENOSYL METHIONINE

S-ADENOSYL METHIONINE

Adomet Adocys

S-ADENOSYL HOMOCYSTEINE

• No disease

MINERALS

• Structural• Component of different important

substances• Cofactor• Nerve impulse• etc.

COFACTORS OF TRANSFERASES

BIOTIN• Biocitin• ATP dependent

carboxylation reactions• Transcarboxylation

DISEASE IS UNCOMMON

•Deficiency of biotinidase•Raw eggs (avidin)•Antibiotics

•Dermatitis•Loss of hair•Paralysis

COENZYME A

• Transfer of acyl groupsPantothenic acid

CoA-SH

• NO DISEASE

• Oxidative decarboxylation of α-keto acids

• Transketolase reaction

THIAMINE PYROPHOSPHATE

THIAMINE PYROPHOSPHATEDEFICIENCY (BERIBERI)

EARLIEST SYMPTOMS• Constipation• Appetite

suppression• Nausea• Mental depression• Peripheral

neuropathy• Fatigue

CHRONIC DEFICIENCY• Severe neurological

symptoms• Ataxia• Mental confusion• Loss of eye

coordination• Cardiomegaly• Cardiac failure• Musculature defects

WERNICKE-KORSAKOFF SYNDROME•Amnesia •Encephalopathy

PYRIDOXAL AND PYRIDOXAMINE

PHOSPHATE

• Glycogenolysis• METABOLISM OF AMINO ACIDS

RacemizationTransaminationNon-oxidative deamination

• DISEASE: NeuritisIsoniazidPenicillamine

Pyridoxol

Pyridoxal

Pyridoxamine

Pyridoxal Phosphate

Pyridoxamine Phosphate

• Pyridoxine (Vit B6)

TETRAHYDROFOLATE

• Transfer of one carbon atom fragment with different oxidation status

• Very important in the synthesis of nucleotides

• DISEASE: Megaloblastic anemia

COFACTORS FROM TETRAHYDROFOLATE

• Transfer of methyl groups

S-ADENOSYL METHIONINE

S-ADENOSYL METHIONINE

Adomet Adocys

S-ADENOSYL HOMOCYSTEINE

• No disease

DISEASE

ADENOSYL COBALAMINE• Vitamin B12

•Adenosyl cobalamine• Metabolism of one atom carbon fragment• Isomerization of methylmalonyl-CoA

Pernicious anemia

Megaloblastic anemia

Nerve demyelination

VITAMIN A

β-Carotene

Retinol All-trans-retinal

11-cis-retinalRetinoic acid

VITAMIN AHormone????? • Interacting with genes:

• growth and differentiation• retinoic acid is involved in the earliest processes of embryogenesis including the differentiation of the three germ layers, organogenesis and limb development.

Abnormal osteogenesis

• Synthesis of glycoproteins and mucopolysaccharides necessary for mucous production and normal growth regulation

Cofactor • Visual pigment

AVITAMINOSIS HYPERVITAMINOSISNight blindness

Follicular hyperkeratinosisSusceptibility to infection

Susceptibility to cancerAnemia

Keratinization of the cornea (xerophthalmia)

Bone pain

Hepatosplenomegaly

Nausea

Diarrhea

VITAMIN E

• Antioxidant agent• Detoxification of free radicals

α-Tocopherol

Vitamin E is a mixture of several related compounds known as tocopherols

Red blood cell fragilityNeurological disordersIncreased risk of certain cancers

DEFICIENCY

VITAMIN K

• Transfer of Hydrogen and electrons• γ-carboxylation of glutamate in several blood

clotting factors (II, VII, IX, X)

• DISEASE: Bleeding

Phylloquinone

MINERALS

• Structural• Component of different important

substances• Cofactor• Nerve impulse• etc.