vitamins and cofactors
TRANSCRIPT
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VITAMINS and COFACTORS
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WATER-SOLUBLE VITAMINS• B1• B2• B6• B12• C• Folate• Biotin• Niacin• CoA
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• Oxidative decarboxylation of a-keto acids
• Transketolase reaction
B1 -THIAMINE PYROPHOSPHATE
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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
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B2 - FLAVIN NUCLEOTIDES
They are derivatives of riboflavin or vitamin B2
• Flavin Mononucleotide (FMN)• Flavin Adenine Dinucleotide (FAD)
Riboflavin (B2)Riboflavin (B2)
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FMN - FLAVIN MONONUCLEOTIDE
• FMN• Riboflavin• Dehydrogenation of
two consecutive carbon atoms
• Dehydrogenation of NAD+ in Electron Transport Chain
Riboflavin (B2)FMN
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FAD - FLAVIN ADENINE DINUCLEOTIDE
• FAD• Riboflavin• Dehydrogenation
of two consecutive carbon atoms
AriboflavinosisRiboflavin (B2)FMNFAD
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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.
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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
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DISEASE:• Pernicious anemia• Megaloblastic anemia• Nerve demyelinization
B12 - ADENOSYL COBALAMINE
REACTIONS:• Metabolism of one carbon atom fragment• Isomerization of methylmalonyl-CoA
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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
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• 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
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SCURVY•Easily bruised skin
•Muscle fatigue
•Soft swollen gums
•Decreased wound healing
•Hemorrhaging
•Osteoporosis
•Anemia
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THF - TETRAHYDROFOLATE
• Transfer of one carbon atom fragment with different oxidation status
• Very important in the synthesis of nucleotides• DISEASE: Megaloblastic anemia
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COFACTORS FROM TETRAHYDROFOLATE
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BIOTIN• Biocitin• ATP dependent
carboxylation reactions• Transcarboxylation
DISEASE IS UNCOMMON
•Deficiency of biotinidase•Raw eggs (avidin)•Antibiotics
•Dermatitis•Loss of hair•Paralysis
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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
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NICOTINAMIDE ADENINE
DINUCLEOTIDE
• NAD+
• Oxidation of one carbon atom
• Feed the Electron Transport Chain
Hey, look at me!!!!
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NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE
• NADP+
• Oxidation of one carbon atom
• Most important source of reduction equivalent for synthesis
Hey, look at me!!!!
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COENZYME A• Transfer of acyl groups
Pantothenic acid
CoA-SH
• NO DISEASE
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FAT-SOLUBLE VITAMINS
• Vitamin A• Vitamin D• Vitamin E• Vitamin K
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VITAMIN A
b-Carotene
Retinol All-trans-retinal
11-cis-retinalRetinoic acid
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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
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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
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VITAMIN K
• Transfer of Hydrogen and electrons• g-carboxylation of glutamate in several blood
clotting factors (II, VII, IX, X)
• DISEASE: Bleeding
Phylloquinone
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Cofactors
• Coenzyme Q• Heme• Lipoamide• Adomet• Adocys• Minerals
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COENZYME QNO VITAMIN
• Carrier of Hydrogen and electrons in the Electron Transport Chain
• Connector of Complex I and II with Complex III
Ubiquinone
Ubihydroquinone
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HEME
HEME AND HEMINE
• CYTOCHROMES• Carrier of electron in
the Electron Transport Chain
• Detoxification of the organism
• CATALASES AND PEROXYDASES
• Detoxification of free radicals
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LIPOAMIDE• Oxidative decarboxylation of a-keto acid
Lipoic acid
Dihydrolipoic acid
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• Transfer of methyl groups
S-ADENOSYL METHIONINE
S-ADENOSYL METHIONINE
Adomet Adocys
S-ADENOSYL HOMOCYSTEINE
• No disease
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MINERALS
• Structural• Component of different important
substances• Cofactor• Nerve impulse• etc.
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COFACTORS OF TRANSFERASES
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BIOTIN• Biocitin• ATP dependent
carboxylation reactions• Transcarboxylation
DISEASE IS UNCOMMON
•Deficiency of biotinidase•Raw eggs (avidin)•Antibiotics
•Dermatitis•Loss of hair•Paralysis
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COENZYME A
• Transfer of acyl groupsPantothenic acid
CoA-SH
• NO DISEASE
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• Oxidative decarboxylation of α-keto acids
• Transketolase reaction
THIAMINE PYROPHOSPHATE
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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
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PYRIDOXAL AND PYRIDOXAMINE
PHOSPHATE
• Glycogenolysis• METABOLISM OF AMINO ACIDS
RacemizationTransaminationNon-oxidative deamination
• DISEASE: NeuritisIsoniazidPenicillamine
Pyridoxol
Pyridoxal
Pyridoxamine
Pyridoxal Phosphate
Pyridoxamine Phosphate
• Pyridoxine (Vit B6)
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TETRAHYDROFOLATE
• Transfer of one carbon atom fragment with different oxidation status
• Very important in the synthesis of nucleotides
• DISEASE: Megaloblastic anemia
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COFACTORS FROM TETRAHYDROFOLATE
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• Transfer of methyl groups
S-ADENOSYL METHIONINE
S-ADENOSYL METHIONINE
Adomet Adocys
S-ADENOSYL HOMOCYSTEINE
• No disease
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DISEASE
ADENOSYL COBALAMINE• Vitamin B12
•Adenosyl cobalamine• Metabolism of one atom carbon fragment• Isomerization of methylmalonyl-CoA
Pernicious anemia
Megaloblastic anemia
Nerve demyelination
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VITAMIN A
β-Carotene
Retinol All-trans-retinal
11-cis-retinalRetinoic acid
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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
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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
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VITAMIN K
• Transfer of Hydrogen and electrons• γ-carboxylation of glutamate in several blood
clotting factors (II, VII, IX, X)
• DISEASE: Bleeding
Phylloquinone
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MINERALS
• Structural• Component of different important
substances• Cofactor• Nerve impulse• etc.