Transcript overview, inorgs, trace nutrients

Section 10: Nutrients and their
functions
• B vitamins
02/03/06
B Vitamins
• The water soluble B-complex vitamins and several related nonvitamins are carriers in group transfer reactions.
Entity Transferred
electron (H’)
electron (H’)
electron (H’)
electron
aldehyde
acyl group
acyl group, electron
alkyl group
carbon dioxide
amino group
methyl, methylene,
or formyl group
1
Coenzyme
NAD, NADP
FMN, FAD
coenzyme Q
heme derivatives
thiamine pyrophosphate
coenzyme A
lipoyl (-enzyme)
coenzyme B12
biotin (-enzyme)
pyridoxal phophate
tetrahydrofolate
Vitamin
niacin (nicotinamide)
riboflavin (B2)
thiamine (B1)
pantothenic acid
B12 (cobalamine)
biotin
pyridoxine (B6)
folic acid (folate)
Overview of B Vitamin Deficiency
• Early studies of beriberi and pellagra focused on something
present in starch that caused the diseases. Later it was
learned that the symptoms were due to something missing.
• The B-complex vitamins are missing in refined foods (white
bread, white rice), which have had the metabolically active
portions of the whole grain removed.
• These vitamins are cofactors for a large number of reaction
schemes that derive energy from food and produce essential
biosynthetic intermediates and products.
• The symptoms of deficiencies are not unique, and it is difficult
to assign a given symptom to a particular missing vitamin.
• Currently, refined foods typically have the B-complex vitamins
added back, and deficiencies are seen only among those
with the most impoverished diets.
2
O
Niacin
O
O
NH 2
O
O
O
P O CH2
N+
H
HO
OH
N+
H
Niacin
• RDA = 15 & 19 mg (F&M).
O
NH 2
• The vitamin niacin is
N
converted to nicotinamide and
N
incorporated into electron
N
N
carriers for catabolic and
O
O P O CH2
anabolic metabolism.
H
O
• Deficiency, when its precursor
OR
HO
tryptophan is also low, leads
NAD+ (R=H) & NADP+ (R=PO3=)
to pellagra (dermatitis,
stomatitis, glossitis).
3
O
Riboflavin
O
H3C
N
H3C
N
H3C
N
NH
O
HC OH
O
HC OH
HC OH
HC OH
HC OH
H2C
HC OH
N
H2C
N
O
O
O P O
N
O
P O CH 2
O
FAD
4
N
H2C
NH
H2C
O
H3C
H
HO
OR
OH
Riboflavin
N
N
• RDA = 1.3 & 1.7 mg (F&M).
• Incorporated into electron
carriers (free and proteinbound).
• Deficiency leads to
cheilosis.
Coenzyme Q
O
H 3C O
CH 3
H 3C O
(
CH 3
)10
O
Coenzyme Q (oxidized form)
• Not a vitamin.
• An electron carrier in the
mitochondrial inner membrane.
5
H
CH3
Heme Derivatives
S
H3C
CH3
H3C
O
O
• Hemes are not vitamins.
• They have roles as
electron carriers and
O
oxygen carriers.
O
6
N
N Fe N
N
S
CH3
Thiamine
NH2
+
N
N
• RDA = 1.1 & 1.5 mg (F&M).
H3 C
N
• The vitamin thiamine is
pyrophosphorylated to make a coenzyme
for several aldehyde transfer reactions in
carbohydrate metabolism.
• Deficiency causes beriberi (light-sensitive
weak eyes, purple tongue).
+
N
N
N
H3C
S
O
CH2 CH2 O
P
O
Thiamine pyrophosphate
7
O
O
CH2 CH2 OH
Thiamine
reactive carbon
NH2
H3C
H3 C
S
P
O
O
Pantothenic Acid
O OH CH3
O
C CH2 CH2 N C CH
O
H
C CH2 OH
CH3
Pantothenic Acid
• Safe and adequate daily dietary intake = 4 - 7 mg.
• The vitamin is incorporated into coenzyme A and
acyl carrier protein of the fatty acid synthase
complex.
• No deficiencies known.
NH2
HS
N
H2C
CH2
O OH CH3
N
C CH2 CH2 N C CH C CH2 O
O
CH3
H
Coenzyme A
8
O
O
N
O
P O P O CH2
H
O
O
OH
HO
N
N
O
H
Lipoic Acid
O
S S
Lipoate
• Not a vitamin.
• Lipoic acid is covalently attached
to active sites by a peptide linkage
to a lysine.
• An acyl and e- carrier.
O
H
H
N H
N
S S
reactive
disulfide
9
O
Lipoamide
• RDA = 2 mg (F&M).
• Absent in plants.
• Required for methyl
transfers, DNA
synthesis, succinyl
CoA synthesis.
• Deficiency, almost
always due to
inadequate
production of a
glycoprotein (intrinsic
factor) in the stomach
lining, causes
pernicious anemia.
10
Cobalamin
5'-deoxyadenosine
H2N
O
O
H2N
H3 C
NH2
O
O
NH2
H3 C
H3 C
N
N
N
N
Co
O
CH3
CH3
N
CH3
CH3
dimethylbenzimidazole
Coenzyme B 12
NH2
O
O
Biotin
HN
• Safe and adequate daily dietary
intake = 30 - 100 mg (F&M).
• Required for CO2 transfers,
malonyl CoA synthesis,
oxaloacetate synthesis.
• Deficiency rare, although it can be
induced by high levels of avidin in
the diet, because avidin binds
biotin very tightly. O
NH
Biotin
O
S
O
reactive nitrogen
HN
NH
lysine side chain
HN
N
S
O
11
enzyme
O
OH
H2C
HO
Pyridoxine
H3C
O
HC
HO
O
N
• RDA = 1.6 & 2.0 mg (F&M).
• The vitamin, pyridoxine, is
O
oxidized and
P O phosphorylated.
O
• Required for various
reactions involving amino
groups.
pyridoxal phosphate
12
N
pyridoxine (vitamin B6)
Schiff base
formation
H 3C
OH
N
H2N
Folic Acid
N
N
O
O
N
HN
OH
O
NH
O
O
Folate
• RDA = 180 & 200 mg (F&M).
• Required for single carbon transfers, purine
biosynthesis.
• Deficiency leads to anemia.
N
H2N
NH
N
OH
O
O
NH
HN
NH
O
O
O
5
13
10
tetrahydrofolate (THF or H4F)
Choline
HO
CH2
CH2
+
N
H3C
choline
• Choline is not a vitamin or a carrier.
• It is a source methyl groups and is
recommended in the diet.
• It has lipotropic effects due to its role in
phospholipid metabolism.
14
CH3
CH3
Conversion of Pyruvate to Acetyl CoA
O
O
O
CH 3
pyruvate
O
HO
thiamine
pyrophosphate
(TPP)
O
-TPP
CH 3
CO2
--TPP
HO
CH 3
lipoamide
TPP
• Pyruvate dehydrogenase complex
O -lipoamide
catalyzes these reactions, which
require several vitamin-derived
CH 3
coenzymes. (section 6 lecture 4)
CoA
• Thiamine pyrophosphate is bound to
+
lipoamide
+
NAD
the active site by NCI’s.
+ NADH
• Covalently bound lipoamide is reduced
when acetyl group forms.
O S -CoA
• Coenzyme A is a substrate.
CH 3
• NAD+ is required to oxidize lipoamide
back to the disulfide state.
15
acetyl CoA
Oral Manifestations of Avitaminosis
DISEASE
CLINICAL SYMPTOMS
BIOCHEMICAL LESION
NUTRIENT
Rickets
enamel hypoplasia*
inadequate synthesis
of calcium binding
protein by intestinal cells
vitamin D
Beriberi
magenta tongue**,
angular cheilosis
impaired carbohydrate
metabolism; many
oxidative
decarboxylations
cannot occur
thiamine (B1)
Scurvy
loose teeth,
bluish-red
gingivitis,
bleeding at
gums
proper collagen
not made; other
hydroxylations
do not occur
ascorbate (C)
Pellagra
stomatitis,
glossitis**,
cheilosis
impaired carbohydrate
metabolism and electron
transport due to
reduced NAD+
niacin
16
Oral Manifestations, con’t.
DISEASE
CLINICAL SYMPTOMS
BIOCHEMICAL LESION
NUTRIENT
none named
stomatitis,
glossitis**,
cheilosis
Impaired carbohydrate
metabolism and electron
transport due to
reduced FAD
riboflavin (B2)
none named
stomatitis
impaired amino
acid metabolism
pyridoxine (B6)
Megaloblastic
anemia
(Sprue)
stomatitis,
glossitis**,
cheilosis
impaired DNA synthesis
due to reduced thymine
production
folate
Pernicious
anemia
glossitis
Impaired methyl group
transfers
vitamin B12
*Enamel hypoplasia is caused also by vitamin A deficiency during tooth development, or by chronic
renal failure-induced decrease in 1,25-dihydroxycholecalciferol production.
**It is often difficult to distinguish glossitis, magenta tongue (an archaic term) or red beefy tongue
as symptoms. Any one can indicate systemic problems due to iron deficiency or
multiavitaminosis.
17
Food Pyramid (USDA 1996)
•Heavy
reliance on
carbohydrates.
•Less than
30%
calories
from fats &
oils.
•Aims for
cardiovascular
health.
•Too many
servings?
18
Revised 1996
Revised Food Pyramid (USDA 2005)
Revised 1996
More fruits,
vegetables,
nuts,
seeds, and
legumes.
Less fat,
oil, sugar,
and meats.
Fats, oils, 2-3/wk !
Sweets, 5/week
Low-fat or
fat-free, 2-3
Revised 2005
For 2000 cal/day
Exercise ~30 min/day
Meat, poultry, fish, 2 or less
Nuts, seeds, legumes, 4-5
Whole
grains.
4-5
4-5
Exercise.
Whole grain
7-8
19
•Study indicates
reduced risks of
major chronic
diseases.
•Healthy eating
index (HEI)
evaluates
carbohydrates,
fats and oils.
•Very low in
animal fats and
refined starch.
•High in fish and
vegetable oils.
•Notice exercise
at base.
•From McCullogh
etal (2002) American
Journal of Clinical
Nutrition 76:1261.
20
Healthy Eating Pyramid
(alternative to USDA pyramid)
Fat and Heart Disease
Locale
Fat Calories
Percent of Total
Rate of Heart
Disease*
Japan
Eastern Finland
Crete
10
38
40
500
3,000
200
*Incidence of coronary heart disease per 10,000 men over ten year period.
What kind of fat is more important than percent
calories from fat.
Willett & Stampter (2002) Scientific American 288:64-71.
21
Fast Food Analysis
breakfast
MCDONALD'S
SAUSAGE MCMUFFIN
WITH EGG
Nutrient
Total
Rec.
%Rec
Calories
2676.02
2300
116.35%
Pro (g)
96.37
63
152.97%
Fat (g)
129.98
76.67
169.53%
lunch
BURGER KING
DOUBLE
CHEESEBURGER
lunch
MCDONALD'S LARGE
FRENCH FRIES
lunch
12 Oz CARBONATED
BEVERAGE-COLA
Carb (g)
333.64
dinner
3 slices medium PIZZA
HUT SUPREME PAN
PIZZA
Na (mg)
4290.17
2400
178.76%
Vit A (IU)
2084.55
5000
41.69%
dinner
16 Oz CARBONATED
BEVERAGE-COLA
Vit C (mg)
40.08
90
44.53%
Sat fat (g)
43.06
25.56
168.47%
Chol (mg)
394.34
300
131.45%
No snacks!
22
From http://nat.crgq.com/mainnat.html
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Extracellular Macromolecules:
Glycosaminoglycans; proteoglycans; mucins