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Biochemistry
Vitamins
1. Water soluble vitamins
2. Fat soluble vitamins
Objectives:
To recognize vitamins by name
To understand their distribution in various food
sources
To understand their role in metabolism
To understand the signs and symptoms of
diseases resulting from deficiencies
Vitamins
A group of organic nutrients required in small
quantities for a variety of biochemical
functions and which , generally , cannot be
synthesized by body and must therefore be
supplied in the diet.
Water soluble vitamins
1. B-complex vitamins
a) B-vitamins in energy metabolism
Thiamine (B1)
Riboflavin (B2)
Niacin (B3)
Biotin
Pantothenic acid
b) B-vitamins in methyl group metabolism conversions
Folic acid
Cobalamin (B12)
c) B-vitamins in metabolic conversions
Pyridoxine (B6)
Pyridoxal
Pyridoxamine
2. Vitamin C
pyruvate dehydrogenase complex
O
O
OCoA
H3C
H3C
S
O
pyruvate
acetyl CoA
+
CO2
Champe and Harvey, p. 106
NH2
NH2
N
N
H3C
H
H
+
N+
N
S
H3 C
N
HO
N
thiamine pyrophosphate TPP O
-
NH2
O
H3C
O
P OO
OH
CH
N+
N
-
S
+
O
O
O
P O
O
thiamine (B1)
H3C
S
H3C
N
first step in pyruvate dehydrogenase complex
O
-
O
P O
O
O
P OO
CO2
Thiamine
Food sources and distribution:
Whole grain, meats, legumes (peas, beans and lentils)
Signs and symptoms of deficiency
Beri-beri:
severe deficiency
Primarily in areas where polished rice is primary food source
Symptoms include dry skin, irritability, disorderly thinking and
progressive paralysis
Wet beriberi-cardiovascular symptoms, cardiac failure
Infants: onset can be rapid, resulting in tachycardia and death
(look to nutritional status of mother)
Wernicke-Korsakoff syndrome:
Primarily associated with severe alcoholism.
Symptoms include apathy, loss of memory
Wandering eye movement
Toxicities, contraindications, and other notes
Only known use in treating deficiency
Commonly given to alcoholics in ER(emergency room)
Excess of any one B-vitamin can cause deficiency of others.
Rubin and Farber, Pathology - 2nd edition, p. 329
O
H3C
H3C
N
N
N
N
H
H
O
CH2
H3C
N
H3C
N
O
N
O
H3C
N
N
H
N
H
OH
OH
OH
OH
riboflavin (B2)
H
H3C
N
O
N
FADH2
CH2
OH
OH
OH
NH2
O
O
O
P
-
O
N
O
N
P
-
O
O
N
O
HO
N
OH
Flavin adenine dinucleotide FAD
O
Riboflavin
Food sources and distribution:
Milk, cheese, meat, leafy vegetables, breads, cereals
Signs and symptoms of deficiency
Sore throat, glossitis, cheilosis (red lips)
Anemia, neuropathy
Toxicities, contraindications and other notes
Only known use in treating deficiency
Excess intake can cause yellow urine
Excess can interfere with B1 & B6
Rubin and Farber, Pathology - 2nd edition, p. 331
H
O
H
NH2
ON
N
+
H
H
niacin (B3)
NADH
O
NH2
H- = H+ + 2e-
N+
O
O
O
O
P O-
N
OH
O
N+
O
P
NH2
OH
NH2
H
O
O
O
N
N
N
-
O
nicotinamide
HO
OH
nicotinamide adenine dinucleotide NAD+
niacin
Food sources and distribution:
Fish, meat, poultry, cereal, nuts
Tryptophan in diet can serve as alternative source
Signs and symptoms of deficiency
Pellagra (pella agra: rough skin)
3D’s: dermatitis, diarrhea, dementia
red, swollen tongue
observed in chronic alcoholics
symptoms reverse within 24H of administration
Toxicities, contraindications and other notes
Harnup’s disease: defective renal and intestinal transport of tryptophan
Fast growing tumors can exhaust tryptophan supply
Excess can cause high BP and uric acid, cardiac arrhythmias
Can lower cholesterol
Rubin and Farber, Pathology - 2nd edition, p. 330
O
HN
O
N H
CO2
O
C N
N H
-
O
Enzyme
S
biotin
Enzyme
S
biotin
Food sources and distribution:
Can be synthesized by intestinal bacteria
Found in most foods
Signs and symptoms of deficiency
Very rare, include dermatitis, muscle pain
Toxicities, contraindications, and notes
Chronic consumption of raw eggs can induce deficiency.
Chronic inflammatory bowel disease can cause deficiency.
H
O
OH
CH3
N
OH
-
O
CH3
O
pantothenic acid
H
O
OH
CH3
N
N
H
SH
O
NH2
O
O P OO
N
O P O-
N
CH3
O
N
O
acceptor site for acetyl group
coenzyme A: CoA
N
OH
OH
pantothenic (B5)
Food sources and distribution:
Ubiquitous
Easily destroyed by heating
Signs and symptoms of deficiency
Very rare
Neuromuscular degeneration
Toxicities, contraindications and other notes
Megadose can cause diarrhea and water retention
B-complex vitamins in energy metabolism and neuropathologies
Review
B-complex vitamins and energy metabolism:
Thiamine B1
TPP, pyruvate dehydrogenase
Riboflavin B2
FAD, FADH2
Niacin B3
NAD+, NADH
Pantothenic acid
coenzyme A
Biotin
decarboxylation reactions
(decarboxylase)
vitamin B6
OH
O
OH
OH
OH
OH
+
+
CH3
N
CH3
N
H
H
pyridoxine
pyridoxal
O
-
-
O
OH
OH
+
N
O
O
NH2
CH3
H
pyridoxamine
O
OH
+
N
CH3
H
pyridoxal phosphate
vitamin B6 - catalyzed reactions
R
O
-
O
O
-
O
O
H N
H
O
O-
-
N
O
-
OH
+
N
O
R
O
O
H
O
O-
O
+
CH3
H
pyridoxal phosphate
N
CH3
H
Schiff base
Transamination: oxaloacetate + glutamate --> aspartate + alpha ketoglutarate
Deamination: serine --> pyruvate
Decarboxylation: histidine --> histamine
Condensation: glycine + succinyl CoA --> gamma-aminolevulinic acid
Pyridoxine (B6)
Food sources and distribution:
Meat, whole-grain breads and cereals, vegetables
Signs and symptoms of deficiency
Skin lesions
Convulsive disorders resulting from low levels of GABA
Needed for NAD+ synthesis
Toxicities, contraindications and other notes
Excess can lead to sensory nerve destruction, loss of feeling in fingers, legs
Extra pyridoxine needed when using ISONAZIDE for treatment of TB
ISONAZIDE binds covalently to pyridoxal phosphate
Champe and Harvey, p. 250
O
S
NH2
O
H2N
sulfanilamide
6-methylpteridine
O
H
N
N
H2N
CH3
para-aminobenzoic acid, PABA
N
N
+
O
-
O
H2N
glutamate
+
NH2
O
O
O-
O
-
O
NH
HN 10
O
H
N
N
H 2N
5
N
N
CH2
O
O-
O
O-
folate, folic acid
O
NH
HN 10
O
H
H2N
N
O-
O
CH2
N
5
N
O
Ofolate, folic acid
N
O
NH
HN 10
O
H
N
5
N
H2N
N
N
H
O-
O
CH2
O
Odihydrofolate, DHF
H
O
NH
O
H
H2N
H
N
5
N
N
N
H
HN 10
H CH
2
H
O
O-
O
Otetrahydrofolate, THF
NH2
H
O
OH
O
serine
O-
O
NH
H
HN 10
O
H
N
5
H
N
O-
O
CH2
O-
tetrahydrofolate, THF
H2N
N
N
H
NH2
O
O
OH
H
H2C
-
glycine
O
N 10
O
H
N
5
H
N
H2N
N
N
H
O
NH
O-
O
CH2
-
O
10-hydroxymethyl-THF
O
- H2O
NH
H2C
O
H
N
5
N
H2N
N
N
H
N 10
CH2
O
O-
O
O5,10 methylene-THF
Stryer, Fig 29-16
Folic acid
Food sources and distribution:
Fresh green vegetables
Cooking can destroy folic acid
Signs and symptoms of deficiency
Hemolytic anemias
Toxicities, contraindications and other notes.
Critical for pregnant women
Megadose can interfere with Zinc absorption.
May interfere with antiepileptic meds (phenobarbitol)
Rubin E, Pathology, p1379
Goodman Gilman, A. The Pharmacological Basis of Therapeutics, p.1245
Champe and Harvey, p. 327
Methyl loading of methionine
O
O
NH
O
H
H2C
N10
N
5
CH2
N
H2N
N
N
H
O-
O
-
O
5,10 methylene-THF
O
NH
H 3C
O
H
N
5
N
H 2N
N
N
H
HN10
CH2
O
methylcobalamin from
vitamin B12
O-
O
O-
5-methyl-THF
NH2
O
S
Ohomocysteine
H
NH2
O
S
Omethionine
CH3
Cobalamin (B12)
Food sources and distribution:
Synthesized only by microorganisms
Deficiency usually results from absorption problem, not availability
Signs and symptoms of deficiency:
Pernicious anemia
Megaloblastic anemia
Neurologic dysfunction
Can result in abnormal fatty acid accumulation in membranes
Toxicities, contraindications and other notes
Substantial stores of B12 are found in the body.
Could take years to develop deficiency.
Caution with patients who have had GI(gastro-intestinal) surgery.
Rubin and Farber, p. 1020
Vitamin C
Food sources and distribution:
Citrus fruits, potatoes
Signs and symptoms of deficiency:
Scurvy results from deficiency in collagen hydroxylation
Results in spongy gums, loose teeth and bleeding under the skin
Toxicities and contraindications:
Can cause oxidation, particularly in presence of free metals
Can be toxic with hemodialysis patients, iron storage diseases
Ascorbate is metabolized to oxalate which can form insoluble precipitates with Ca++
Result in low Ca++, kidney stones, heart deposits.
Vitamin C and collagen synthesis
OH
O
O
OH
HO
OH
vitamin C: ascorbic acid
sugar attachment site
OH
H
N
H
N
N
O
O
proline
H
N
H
N
N
O
O
hydroxyproline
Rubin and Farber, Pathology - 2nd edition, p. 333
Vitamin C and hydroxyl radical formation
2
O2
+ 2H
+
superoxide dismutase
H2O2 + O2
hydrogen peroxide
superoxide
catalase
2 H2O2
2 H2O + O2
Fenton reaction
H2O2 + Fe2+
HO


Fe3+ + HO
ascorbic acid
DNA damage
lipid peroxidation
-
+ HO
Review:
Diseases associated/resulting from deficiencies in water soluble vitamins:
BeriBeri: Vit B1
Wernicke-Korsakoff syndrome: Vit B1
Pellagra: Vit B3
Pernicious anemia: B12
Megaloblastic anemia: B12
Scurvy: Vit C
Fat-soluble vitamins
Vitamin A
Vitamin D
Vitamin E
Vitamin K
Vitamin A
Food sources and distribution:
Low fat dairy products, deep yellow, orange vegetables
Function: Vitamin A(retinol) is the precursor of retinel, the lightsensitive group in rhodopsin and other visual pigments.
Signs and symptoms of deficiency:
Night blindness, dry eyes and skin
Slow growth in children
Lowered resistance to infection
Toxicities and contraindications:
Overdose can result in dry skin, headache
Can result in birth defects in pregnant women
Can cause liver damage
Vitamin A derivatives (isotretinoin, accutane) can cause
birth defects and has been associated with suicide.
H3C
CH3
CH3
CH3
H3C
CH3
CH3
CH3
CH3
-carotene
CH3
CH3
CH3
CH2OH
CH3
CH3
all-trans-retinol
CH3
Rubin and Farber, Pathology - 2nd edition, p. 328
http://www.cnn.com/2002/US/01/08/plane.suicide.mother/index.html
Goodman and Gilman, The Pharmacological Basis of Therapeutics, p. 1599
Vitamin D
Food sources and distribution:
Egg yolks, fortified milk, fish oil, sun exposure
Function: A metabolite of vitamin D is a hormone that
regulates the metabolism of calcium and phosphorus.
Signs and symptoms of deficiency:
Rickets in children
Osteomalacia (osteoporosis) in adults
Toxicities and contraindications:
The most toxic of vitamins in excess
Calcium deposits in heart, hypertension, high cholesterol
Fragile bones
Vitamin D
7-dehydrocholesterol
HO
UV light
kidney hydroxylation
activated by parathyroid
hormone when Ca++ is low
25
OH
HO
1
liver hydroxylation
HO
1,25 dihydroxy cholecalciferol (vitamin D3)
(acts as a hormone-transcription factor activating expression
of Ca++-binding proteins in intestine and bone)
Robbins, Pathologic Basis of Disease – 5th Edition, p. 1221
Vitamin E
Food sources and distribution:
Poultry, seafood, seeds, nuts, whole wheat
Function: Reacts with and neutralizes reactive oxygen species
such as hydroxyl , radicals before they can oxidize unsaturated
membrane lipids, damaging cell structure(antioxidant)
Signs and symptoms of deficiency:
very rare , Unknown in humans, in animal may cause
infertility
Toxicities and contraindications:
Excessive bleeding, reduced sexual function
vitamin E
CH3
H3C
O
CH3
H3C
HO
CH3
-tocopherol
Vitamin K
Food sources and distribution:
Made by intestinal bacteria
Spinach, leafy vegetables, oats, bran, potatoes
Function: required for normal blood clotting(blood
coagulation)
Signs and symptoms of deficiency:
Excess bleeding, bleeding gums
Toxicities and contraindications:
Jaundice in infants
vitamin K
O
O
-
O
menaquinone (vitamin K2)
Ca++
O-
O
O
N
H
required for the carboxylation of glutamate to -carboxyglutamate
allows proteins to bind calcium
important in blood clotting
newborn infants usually get a vitamin K shot
O