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Transcript
Chapter 9
The Water-Soluble Vitamins
2009 Cengage-Wadsworth
General Characteristics of
Vitamins
• Organic compounds with
regulatory functions
– Essential in the diet
• Water-soluble & fat-soluble
handled differently in the body
• DRIs estimate needed intakes
– RDAs, AIs, ULs, & EARs
2009 Cengage-Wadsworth
Vitamin C (Ascorbic Acid)
• Sources
– Fruits & vegetables
• Digestion, absorption, transport, &
storage
–
–
–
–
–
No digestion required
Absorption by SVCT1 & SVCT2
Oxidation prior to absorption
Absorption decreases with intake
Transported primarily in free form
2009 Cengage-Wadsworth
Vitamin C (Ascorbic Acid)
• Functions and mechanisms of
action
– Collagen synthesis
– Carnitine synthesis
– Tyrosine synthesis & catabolism
– Neurotransmitter synthesis
• Norepinephrine
• Serotonin
• Other neurotransmitters & hormones
2009 Cengage-Wadsworth
Vitamin C (Ascorbic Acid)
– Microsomal metabolism
– Antioxidant activity
– Pro-oxidant activity
– Other functions
• Colds
• Cancer
• Cardiovascular disease
• Cataracts
2009 Cengage-Wadsworth
Vitamin C (Ascorbic Acid)
• Interactions with other nutrients
– Iron
– Copper
• Metabolism and excretion
– Excreted or oxidized to dehydroascorbate
• Recommended Dietary Allowance
– Men: 90 mg; women: 75 mg
– Pregnancy: 100 mg; lactation: 120 mg
– + 35 mg for smokers
2009 Cengage-Wadsworth
Vitamin C (Ascorbic Acid)
• Deficiency
– Scurvy
• Toxicity
– UL = 2 g
• Assessment of nutriture
– Plasma & serum concentrations
2009 Cengage-Wadsworth
Thiamin (Vitamin B1)
• Sources
– Meats, legumes, grains
• Digestion, absorption, transport, &
storage
– Antithiamin factors
– Absorption in jejunum, by diffusion or
carriers: ThTr1 & ThTr2
– Ethanol interferes
– Transported free, bound to albumin, or as
thiamine monophosphate (TMP)
2009 Cengage-Wadsworth
Thiamin (Vitamin B1)
• Functions and mechanisms of
action
– Coenzyme roles
• Energy transformation
• Synthesis of pentoses & NADPH
– Noncoenzyme roles: membrane &
nerve conduction
2009 Cengage-Wadsworth
Thiamin (Vitamin B1)
• Metabolism & excretion
– Excreted intact or catabolized
• Recommended Dietary Allowance
– Men: 1.2 mg; women: 1.1 mg
– Pregnancy: 1.4 mg; lactation: 1.5 mg
• Deficiency: beriberi
–
–
–
–
Dry beriberi
Wet beriberi
Acute beriberi
Wernicke-Korsakoff syndrome
2009 Cengage-Wadsworth
Thiamin (Vitamin B1)
• Toxicity
– Little danger with oral intake; no UL
• Assessment of nutriture
– Measuring erythrocyte transketolase
activity in whole blood
– Measuring thiamine in blood or urine
2009 Cengage-Wadsworth
Riboflavin (Vitamin B2)
• Sources
– Milk/dairy, eggs, meat, legumes
• Digestion, absorption, transport, &
storage
– Riboflavin as FAD, FMN & riboflavin
phosphate freed prior to absorption
– Absorbed by saturable, energydependent carrier mechanism in
proximal small intestine
2009 Cengage-Wadsworth
Riboflavin (Vitamin B2)
– Phosphorylated to FMN & then
dephosphorylated back to riboflavin
– Riboflavin transported to liver for
conversion to FMN & FAD
– Most flavins in systemic plasma are
riboflavin
2009 Cengage-Wadsworth
Riboflavin (Vitamin B2)
• Functions &
mechanisms of
action
– Flavoproteins
• Electron transport
chain
• Oxidative
decarboxylation of
pyruvate
• Succinate
dehydrogenase
• Acyl CoA
dehydrogenase
• Sphinganine oxidase
2009 Cengage-Wadsworth
• Xanthine oxidase
• Aldehyde oxidase
• Pyrodoxine
phosphate oxidase
• Active form of
folate
• Choline catabolism
• Monoamine
oxidase
• Glutathione
reductase
• Thioredoxin
reductase
Riboflavin (Vitamin B2)
• Metabolism & excretion
– Excreted primarily in urine; small
amount in feces
• Recommended Dietary Allowance
– Men: 1.3 mg; women 1.1 mg
– Pregnancy: 1.4 mg; lactation: 1.6 mg
2009 Cengage-Wadsworth
Riboflavin (Vitamin B2)
• Deficiency: ariboflavinosis
• Toxicity
– None reported; no UL
• Assessment of nutriture
– Measuring activity of erythrocyte
glutathione reductase
– Cellular & urinary concentrations
2009 Cengage-Wadsworth
Niacin (Vitamin B3)
• Sources
– Fish, meats, grains, seeds, legumes
– Synthesis in liver from tryptophan
• Digestion, absorption, transport, &
storage
–
–
–
–
NAD & NADP hyrolyzed to free nicotinamide
Absorbed in small intestine & stomach
Absorbed mostly by passive diffusion
Transported primarily as nicotinamide, & as
nicotinic acid
2009 Cengage-Wadsworth
Niacin (Vitamin B3)
• Functions & mechanisms of action
– Coenzymes
• Oxidative reactions
• Reductive biosynthesis
• Folate metabolism
– Nonredox roles
• Donor of ADP-ribose for posttranslational
modification of proteins & formation of
cyclic ADP-ribose
2009 Cengage-Wadsworth
Niacin (Vitamin B3)
• Metabolism & excretion
– NAD/NADP degraded to nicotinamide
& ADP-ribose
– Nicotinamide methylated & oxidized
in liver to products excreted in urine
• Recommended Daily Allowance
– Men: 16 mg NE; women 14 mg NE
– Pregnancy: 18 mg NE; lactation: 17
mg NE
2009 Cengage-Wadsworth
Niacin (Vitamin B3)
• Deficiency: pellagra
• Toxicity
– Large doses used to treat
hypercholesterolemia
– Side effects with doses >1 g/day
– UL = 35 mg
• Assessment of nutriture
– Measuring urinary metabolites
– Erythrocyte NAC concentrations
– Ratio of NAD to NADP
2009 Cengage-Wadsworth
Pantothenic Acid
• Sources - virtually all foods
• Digestion, absorption, transport, &
storage
– CoA form hydrolyzed to free form
– Absorbed principally in jejunum by
passive diffusion
– Low concentrations - absorbed by Nadependent multivitamin transporter/
carrier (SMVT)
2009 Cengage-Wadsworth
Pantothenic Acid
– Transported in free form in blood
• Functions & mechanisms of action
– Component of CoA & 4’phophopantetheine
– Nutrient metabolism
– Prosthetic group for actyl carrier
protein (ACP) - FA synthesis
– Acetylation of proteins, sugars, drugs
2009 Cengage-Wadsworth
Pantothenic Acid
• Metabolism & excretion
– Excreted intact in urine, small
amounts in feces
• Adequate Intake
– Adults: 5 mg
– Pregnancy: 6 mg; lactation: 7 mg
2009 Cengage-Wadsworth
Pantothenic Acid
• Deficiency: burning feet syndrome
• Toxicity
– None reported
• Assessment of nutriture
– Blood concentrations
– Urinary pantothenate excretion
2009 Cengage-Wadsworth
Biotin
• Sources
– Widely distributed in foods
– Made by large intestinal bacteria
• Digestion, absorption, transport, &
storage
– Protein-bound: digestion by proteolytic
enzymes
– From food: absorbed primarily in jejunum,
followed by ileum
2009 Cengage-Wadsworth
Biotin
– From bacteria: absorbed in proximal
& midtransverse colon
– Absorption method
• Pharmacologic doses: passive diffusion
• Otherwise: SMVT
– Transported in free, unbound state
2009 Cengage-Wadsworth
Biotin
• Functions & mechanisms of action
– Coenzyme roles
•
•
•
•
Pyruvate carboxylase
Acetyl CoA carboxylase
Propionyl CoA carboxylase
-methylcrotonyl CoA carboxylase
– Non-coenzyme roles
• Cell proliferation, gene silencing, & DNA repair
• Gene expression & cell signaling
2009 Cengage-Wadsworth
Biotin
• Metabolism & excretion
– Biotin holocarboxylases catabolyzed
to biotin oligopeptides & then biocytin
– Biocytin degraded to lysine & biotin
– Metabolites excreted in urine
– Biotin from bacteria that is not
absorbed excreted in feces
2009 Cengage-Wadsworth
Biotin
• Adequate Intake
– Adults & pregnancy: 30 µg
– Lactation: 35 µg
• Deficiency
– Rare but serious
• Toxicity
– None reported
• Assessment of nutriture
– Urinary excretion is a sensitive indicator
2009 Cengage-Wadsworth
Folate
• Sources
– Mushrooms, green vegetables,
peanuts, legumes, lentils, fruits, liver
• Digestion, absorption, transport, &
storage
– Polyglutamate forms hydrolyzed to
monoglutamate form
– Absorbed with folate-binding proteins
2009 Cengage-Wadsworth
Folate
– Reduced to THF in enterocytes, then
metylated to 5-methyl THF or
formylated
– Transported in portal circulation as 5methyl THF
– Found as a monoglutamate in blood
2009 Cengage-Wadsworth
Folate
• Functions & mechanisms of action
– Amino acid metabolism
• Histidine
• Serine & glycine
• Methionine
• Possible relationship with diseases
– Purine & pyrimidine synthesis/
nucleotide metabolism
• Other relationships with diseases
2009 Cengage-Wadsworth
Folate
• Interactions with other nutrients
– Vitamin B12
• Metabolism & excretion
– Excreted in urine & feces
• Recommended Dietary Allowance
– Adults: 400 µg DFE
– Pregnancy: 600 µg DFE; lactation
500 µg DFE
2009 Cengage-Wadsworth
Folate
• Deficiency: megaloblastic
macrocytic anemia
• Toxicity
– UL = 1 mg synthetic (non-natural)
• Assessment of nutriture
– Plasma, serum or RBC concentration
– N-formiminoglutamate excretion
– Deoxyuridine suppression test
2009 Cengage-Wadsworth
Vitamin B12 (Cobalamin)
• Sources - animal products
• Digestion, absorption, transport, &
storage
– In the stomach
• Released from proteins/polypeptides
• Binds to an R protein
2009 Cengage-Wadsworth
Vitamin B12 (Cobalamin)
– In the duodenum
• R protein hydrolyzed - free cobalamin
• Binds to intrinsic factor
– In the ileum
• Absorbed via binding with receptors
(cubilins)
• Binds to transcobalamin II for transport
– Enterohepatic circulation
2009 Cengage-Wadsworth
Vitamin B12 (Cobalamin)
– In blood, bound to 1 of 3 cobalamins
• TCII - main protein that carries newly
absorbed cobalamin in 1-1 ratio
• TCI & TCIII - exact functions unknown
– Can be stored & retained in the body
for long periods
2009 Cengage-Wadsworth
Vitamin B12 (Cobalamin)
• Functions & mechanisms of action
– Conversion of homocysteine to
methionine (methylcobalamin)
– Conversion of L-methylmalonyl CoA
to succinyl CoA (adenosylcobalamin)
• Metabolism & excretion
– 0.1%/day excreted in bile, bound to
R protein
2009 Cengage-Wadsworth
Vitamin B12 (Cobalamin)
• Recommended Dietary Allowance
– Adults: 2.4 µg
– Pregnancy: 2.6 µg; lactation: 2.8 µg
• Deficiency: megaloblastic
macrocytic anemia
– Also neuropathy
– Usually caused by inadequate
absorption
2009 Cengage-Wadsworth
Vitamin B12 (Cobalamin)
• Toxicity
– None observed
• Assessment of nutriture
– Serum concentrations
– Serum methylmalonyl CoA or
methylmalonic acid & homocysteine
– Doxyuridine supression test
– Schilling test
2009 Cengage-Wadsworth
Vitamin B6
• Sources
– Meats, whole grains, vegetables,
some fruits, nuts
• Digestion, absorption, transport, &
storage
– Dephosphorylated to PN, PL, or PM
– Primarily absorbed by passive
diffusion in jejunum
2009 Cengage-Wadsworth
Vitamin B6
– PN, PL & PM released into portal
blood
– Most converted to PLP in liver
– Most PLP transported bound to
albumin
– PL, PN, PM & PMP also found in blood
2009 Cengage-Wadsworth
Vitamin B6
• Functions &
mechanisms of
action
• Cleavage
• Racemization
• Other synthetic
reactions
• Glycogen
degradation
– Coenzymes
• Transmination
• Decarboxylation
• Transulfhydration &
desulhydration
• Dehydration (also
called elimination)
or deamination
– Noncoenzyme
role: steroid
hormone action
2009 Cengage-Wadsworth
Vitamin B6
• Metabolism & excretion
– 4-pyridoxic acid (PIC) - metabolite
– Excreted in urine
• Recommended Dietary Allowance
– Men 19-50: 1.3 mg; 51 & >: 1.7 mg
– Women 19-50: 1.3 mg; 51 & >: 1.5
mg
– Pregnancy: 1.9 mg; lactation: 2.0 mg
2009 Cengage-Wadsworth
Vitamin B6
• Deficiency
– Rare, but more likely in elderly,
alcoholics, people on certain drugs
• Toxicity
– Sensory & peripheral neuropathy
– UL = 100 mg
2009 Cengage-Wadsworth
Vitamin B6
• Assessment of nutriture
– Plasma PLP concentrations
– Xanthurenic acid excretion following
tryptophan loading
– Urinary B6 & 4-pyridoxic acid
– Erythrocyte transaminase activity
before & after adding B6
2009 Cengage-Wadsworth
Perspective 9
Genetics & Nutrition:
The Possible Effect on Human
Folate Needs & Risk to
Chronic Disease
2009 Cengage-Wadsworth
Genetics & Nutrition
• Introduction
• N5,N10 methylenetetrahydrofolate
reductase & its genetic variants
– Ethnic differences in genetic
variations in MTHFR
– MTHFR variations & risk to chronic
disease
• Summary
2009 Cengage-Wadsworth