Chapter 13

Micronutrients in Energy and

Amino Acid Metabolism
Outlines
• Water-Soluble Vitamin Overview
• Thiamin
• Riboflavin
• Niacin
• Pantothenic Acid
• Biotin
• Chromium (Cr)
• Vitamin B-6
• Folate
• Vitamin B-12
• Manganese (Mn)
• Molybdenum (Mo)
• Choline
• Iodine (I)
• Sulfur 2
Outlines
• Water-Soluble Vitamin Overview
• Thiamin
• Riboflavin
• Niacin
• Pantothenic Acid
• Biotin
• Chromium (Cr)
• Vitamin B-6
• Folate
• Vitamin B-12
• Manganese (Mn)
• Molybdenum (Mo)
• Choline
• Iodine (I)
• Sulfur 3
Cofactors: A Common Role of B-
Vitamins and Some Minerals
• Apoenzyme: inactive form of
enzyme
• Cofactor: combines with
apoenzyme to form holoenzyme
– co-enzymes: organic cofactor
• Utilized in energy conversion
• necessary for enzyme activity

• Holoenzyme: active form of enzyme

(i.e., apoenzyme + cofactor) 4
The Enzyme-Coenzyme Interaction

Inactive
enzyme
(apoenzyme)
+

Vitamin
coenzyme

Active
enzyme
(holoenzyme)

5
Vitamin B and their coenzyme form
B-Vitamins Coenzyme form 縮寫
Thiamin Thiamin pyrophosphate TPP
TPP

Riboflavin Flavin adenine dinucleotide FAD

FAD
FMN
Flavin mononucleotide FMN
Niacin Nicotinamide adenine dinucleotide NAD
NAD
NADP
Nicotinamide adenine dinucleotide NADP
phosphate
Pantothenic Coenzyme A CoA
CoA
acid
Vitamin B6 Pyridoxal phosphate PLP
PLP
Folic acid Tetrahydrofolic acid THFA
THFA
6
Vitamin B12 Methylcobalamin
7
8
General functions of vitamins
• Energy metabolism
– Thiamin
– Riboflavin
– Niacin
– Pantothenic Acid
– Biotin
• Blood Formation and Clotting
– Vitamin B-6
– Vitamin B-12
– Folate
– Vitamin K
9
Enrichment and Fortification of
Grains
•Grains
–Milling of grains removes germ胚芽 and husk殼,
which contain many vitamins, minerals and fibers
–important source of B vitamins

Starch rich 胚乳

10
Outlines
• Water-Soluble Vitamin Overview
• Thiamin
• Riboflavin
• Niacin
• Pantothenic Acid
• Biotin
• Chromium (Cr)
• Vitamin B-6
• Folate
• Vitamin B-12
• Manganese (Mn)
• Molybdenum (Mo)
• Choline
• Iodine (I)
• Sulfur 11
Thiamin 硫胺 維生素B1
• 易溶於水，因此
•Contains sulfur and nitrogen group 容易從食物中流
•Destroyed by alkaline and heat 失到水中
•Coenzyme: Thiamin pyrophosphate • 易受光、鹼、熱、
(TPP) 金屬離子的破壞，
是維生素中最不
穩定的一種

P~P
pyrophosphate

12
Thiamin 硫胺 維生素B1
•Foods
–Pork, sunflower seeds and legumes
•Needs and upper level
–RDA
• 1.2
1.2mg/day
mg/day men

• 1.11.1mg/day
mg/day women

–DV 1.5 mg/day

–Average North American intake is 1.2-2.0 mg/day
–No UL
13
14
Absorption, transport, storage
and excretion of thiamin
•Absorbed in the jejunum空腸 by a
carrier-mediated system
– by sodium-dependent active absorption
process
•Transported by RBC in the blood
•Poorly stored; small reserve in liver
and muscles
•Excess quickly excreted in the urine
15
Functions of Thiamin
• Coenzyme
thiaminpyrophosphate
– thiamin pyrophosphate (TPP)
(TPP)
• Required for carbohydrate, branched chain
amino acid (BCAA) reactions

16
Functions of Thiamin
• Decarboxylation reactions
Decarboxylation reactions
– Pyruvate  acetyl CoA during the aerobic
metabolism of glucose
– -ketoglutarate  succinyl CoA during citric
acid cycle
– These reactions also require CoA (pantothenic
acid), NAD (niacin), and FAD (riboflavin)
• Coenzyme for transketolase
– Convert glucose to other sugars
– pentose phosphate pathway(PPP) that forms
DNA and RNA 17
Functions of Thiamin

Oxidative decarboxylation

18
Thiamin
• Deficiency
– Beriberi腳氣病
Beriberi腳氣病
• Dry beriberi
neurological
– Nervous and muscular system (neurological
symptoms only )
Peripheralneuropathy
– Peripheral neuropath 周邊神經病變
• Wet beriberi
– neurological symptoms
cardiovascular system
– affects cardiovascular system, leading to
congestive heart failure充血性心臟病
• Infantile beriberi
19
Thiamin
• Deficiency
– Wernicke-Korsakoff syndrome
• Cerebral beriberi
– Vision changes、Ataxia運動失調、Impaired mental

function
alcoholism
• Alcohol use；alcoholism

20
Outlines
• Water-Soluble Vitamin Overview
• Thiamin
• Riboflavin
• Niacin
• Pantothenic Acid
• Biotin
• Chromium (Cr)
• Vitamin B-6
• Folate
• Vitamin B-12
• Manganese (Mn)
• Molybdenum (Mo)
• Choline
• Iodine (I)
• Sulfur 21
Riboflavin核黃素 維生素B2
• Coenzymes:
–Flavin mononucleotide
(FMN)
FMN
–Flavin adenine dinucleotide
(FAD)
FAD
• Yellow color

22
Riboflavin核黃素
• Foods
–Milk,
Milk enriched grains, eggs and meat
• Needs and upper level
–RDA
1.3mg/day
• Men: 1.3 mg/day
• Women:1.11.1mg/day
mg/day
–DV: 1.7 mg/day
–Average North American intake is 1.5-2.1
mg/day
–No UL
• Sensitive to uv
uv radiation (sunlight)
sunlight
• Stored in paper, plastic containers 23
24
Absorption, transport, storage and
excretion
• Absorption
– Released from protein-bound form by HCl in
stomach
– active transport
in the small intestine
– facilitated diffusion
• Transport
– By a protein carriers
• storage
– Small amount stored in liver
• excretion
– excess excreted by urine 25
Functions of Riboflavin
• Coenzymes in oxidation-reduction
reactions
– flavin mononucleotide (FMN)
– flavin adenine dinucleotide (FAD)

26
Functions of Riboflavin
• Energy metabolism
– CAC
• Succinate  fumarate
• Enzyme: succinate dehydrogenase
• Coenzyme: FAD
– β-oxidation
• Fatty acid  acetyl CoA
• Enzyme: fatty acyl dehydrogenase
• Coenzyme: FAD
– FMN Shuttles H atoms to the electron
transport system
27
Functions of Riboflavin
• Activation of other B vitamin
– Tryptophan  niacin requires FAD
– Formation of PLP(B6 coenzyme) requires FMN
– Riboflavin participates in folate metabolism
• Antioxidant function
– Metabolism of oxidized glutathione
– GSSG + FADH2 → 2 GH + FAD (glutathione
reductase)

28
Deficiency of Riboflavin
• Ariboflavinosis核黃素缺乏症
• Occurs within 2 months, usually in
combination with other deficiencies
• Susceptible populations
– Alcohol abusers
– Long-term users of phenobarbitol
– Avoidance of milk products

29
Deficiency of Riboflavin
• Symptoms
口腔炎
– Stomatitis: 口腔炎
– Glossitis: 舌炎
舌炎
口角炎
– angular cheilotis : 口角炎
– Seborrheic dermatitis: 脂溢性皮膚炎
脂溢性皮膚炎
– Eye disorder
– Throat disorder
– Nervous system disorder

30
Outlines
• Water-Soluble Vitamin Overview
• Thiamin
• Riboflavin
• Niacin
• Pantothenic Acid
• Biotin
• Chromium (Cr)
• Vitamin B-6
• Folate
• Vitamin B-12
• Manganese (Mn)
• Molybdenum (Mo)
• Choline
• Iodine (I)
• Sulfur 31
Niacin菸鹼酸 Vit B3
•自然界中以兩種形式存在
–Nicotinic acid (niacin)菸鹼酸
–Nicotinamide (niacinamide)菸鹼醯胺

32
Niacin菸鹼酸 Vit B3
• Coenzyme
– Nicotinamide adenine dinucleotide (NAD)
(NAD)

– Nicotinamide adenine dinucleotide

phosphate (NADP)
NADP

33
Niacin in foods
Heat stable；Little
• Heat stable cooking losses
• 又稱 PP PPfactor
factor (Pellagra癩皮病 prevent factor)
• Foods
tryptophan
–Available as niacin or synthesized from tryptophan
–Poultry家禽肉 , meat and fish
–RDA expressed as niacin equivalents
–人體內可由 色胺酸(tryptophan)
色胺酸(tryptophan) 合成，因此不易缺乏
60 mg
–60 mg tryptophan can be converted into 1 mg
1 mg
niacin (egg, milk)
–60 mg tryptophan =1 mg niacin ； 1 g of protein
= 10 mg tryptophan
–Estimate by dividing the total grams of
34
protein by 6
35
Niacin Needs
•RDA
16mg
–16 mg NE/day
NE/day for men
14mg
–14 mg NE/day
NE/day for women
–DV 20mg/day
–U.S. intake exceeds RDA
•upper level
–UL 35 mg/day applies only to supplements and
fortification
–Toxicity effects
• Flushing of skin: 皮膚發紅
• Itching
• Nausea, vomit 噁心，嘔吐
• Liver damage 36
Absorption, transport, storage
and excretion
• Readily absorbed from the stomach and
small intestine
• Absorption: active transport and passive
diffusion
– Bioavailability of niacin in low (30%) in some
grains, especially corn (bound to protein)
– Soaking corn in lime water石灰水 improves
bioavailability of niacin
• Transported from the liver to all of the
tissues where it is converted to coenzymes
37
• Excess excreted in urine
 Functions of Niacin
• Coenzyme (NADH and
NADPH) in oxidation-
reduction reactions
• Required for catabolism of
carbohydrate, fat and
protein
–Glycolysis
–Citric acid cycle
–Alcohol dehydogenase
• Anabolic reactions use
NADPH
–Fatty acid synthesis
38
• in at least 200 reactions
Niacin-Deficiency Diseases
• Pellagra 癩皮 (多發生於以玉米為主食的地區)
Pellagra癩皮病
–Only dietary deficiency disease to reach epidemic proportions
in the U.S.
–Occurs in 50-60 days
–Prevented with an adequate protein diet
–Consequences of deficiency (3D症狀，嚴重時會導致死亡4D)
• Diarrhea: 腹瀉
• Dementia: 失憶症
• Dermatitis: 皮膚炎
–Enrichment Act of 1941
–Susceptible populations
• Those who consume (untreated) corn as main staple主食
• Hartnup disease夏立氏疾病: tryptophan metobolism 異常
• Alcoholism 39
Pharmacologic Use of Niacin
• Pharmacological use
– Nicotinic Acid: 60 x RDA (1 - 2 g/d) can lowers
Triglycerides, increases HDL-C
– Slow/ reverse progression of atherosclerosis with
diet and exercise

40
Outlines
• Water-Soluble Vitamin Overview
• Thiamin
• Riboflavin
• Niacin
• Pantothenic Acid
• Biotin
• Chromium (Cr)
• Vitamin B-6
• Folate
• Vitamin B-12
• Manganese (Mn)
• Molybdenum (Mo)
• Choline
• Iodine (I)
• Sulfur 41
 Pantothenic Acid泛酸
•Foods
–supplied by a wide variety of foods
–Meat, milk and many vegetables

42
43
Pantothenic Acid Needs
• Needs and upper level
–AI
• 5 mg

–DV
• 10 mg

–No UL

44
Absorption, Transport, Storage, and
Excretion of Pantothenic Acid
• Consumed as coenzyme A in diet, released
during digestion in small intestine
• Absorbed as pantothenic acid or derivative
from small intestine
• Minimal storage as coenzyme in liver
• Readily excreted in urine

45
Functions of Pantothenic Acid
• Part of Coenzyme-A
–Essential for metabolism of carbohydrate, fat,
protein, and alcohol (acetyl CoA)
• Donates fatty acids to proteins
• Forms acyl carrier protein involved in fatty
acid elongation

46
Pantothenic Acid Deficiency
• Rare; only experimentally induced
• Symptoms
– Fatigue疲勞
– Headache
– Impaired muscle coordination
– GI tract disturbances

47
Outlines
• Water-Soluble Vitamin Overview
• Thiamin
• Riboflavin
• Niacin
• Pantothenic Acid
• Biotin
• Chromium (Cr)
• Vitamin B-6
• Folate
• Vitamin B-12
• Manganese (Mn)
• Molybdenum (Mo)
• Choline
• Iodine (I)
• Sulfur 48
 Biotin生物素
•Coenzyme form:
Coenzyme form: biocytin生物胞素
biocytin生物胞素

與protein的
lysine 鍵結形
成 biocytin
生物胞素49
Sources of Biotin
Microbial Synthesis
• Food and Microbial Synthesis
–Two forms in food
• Free vitamin
Biocytin protein-bound form
• Biocytin:
–Food sources
• Whole grains
• Eggs
• Nuts
• Legumes
• Bacteria in the large intestine synthesize
biotin; bioavailabilty from this sources is
unknown because most efficient absorption
occurs in small intestine
50
51
Biotin Needs
• Needs and upper level
–AI 30 μg
–DV 300 μ g
–No UL
• Avidin
Avidin (卵白素)
(卵白素) inhibits absorption (生蛋白中含有抗生物
素(avidin)的醣蛋白，它能與生物素結合，而使之不能為小腸所吸收，

因此長期吃生蛋白者會造成生物素的缺乏)

–> a dozen raw eggs a day to cause this effect

52
Absorption, Transport, Storage,
and Excretion of Biotin
• Absorption of Biotin
–In small intestine, biotinidase releases biotin from
biocytin and other biotin-dependent enzymes
found in foods
–Free biotin absorbed in small intestine by sodium-
dependent carrier
• Storage of Biotin: small amounts in muscles,
liver, and brain
• Excretion of Biotin: urine, minor amount in
bile 53
 Functions of Biotin
• Functions
adds CO
– Coenzyme that adds CO2
carboxylase reactions
– carboxylase reactions ； carboxyl carrier；單碳物質
的固定作用
– Required for metabolism of carbohydrates, fats
and proteins
• Pyruvate  oxaloacetate

• Catabolism of threonine, leucine, methionine, and

isoleucine for energy

• Acetyl-CoA  malonyl丙二醯 CoA in fatty acid synthesis54

 Functions of Biotin
•Functions

55
Deficiency of Biotin
•Deficiency
–Rare
–High-risk populations
• 1/112,000 infants has genetic defect that results in low
biotinidase
biotinidase
avidin
• Ingestion of large amounts of raw egg whites (avidin
binds biotin; denatured by cooking)
–Symptoms
• Skin rash
• Hair loss
• Convulsions痙攣
• Impaired growth 56
Outlines
• Water-Soluble Vitamin Overview
• Thiamin
• Riboflavin
• Niacin
• Pantothenic Acid
• Biotin
• Chromium (Cr)
• Vitamin B-6
• Folate
• Vitamin B-12
• Manganese (Mn)
• Molybdenum (Mo)
• Choline
• Iodine (I)
• Sulfur 57
Food Sources of Chromium

•Little information
•Egg yolk
•Bran, whole grain, cereal
•Organ meat, meat, beer
•Plant source dependent on soil content

58
Chromium Needs
• AI
– 35 μg/d for men (19 - 50 years)
– 25 μg/d for women (19 - 50 years)
– 30 μg/d for men (50+years)
– 20 μg/d for women (50+years)
• Average intake meets the AI
• DV = 120 μg
• No UL

59
Absorption, Transport, Storage,
and Excretion of Chromium鉻
•Chromium鉻 from food is poorly
absorbed (0.5%~2%)
•Concentration of chromium is very low
in the body
•Bound to transferrin in the blood
•Stored in bones, spleen, liver, kidneys
•Excretion via the feces

60
Functions of Chromium

•Glucose uptake into the cell

–促進insulin與細胞膜接觸，加速細胞吸收glucose
–是Glucose tolerance factors(Cr3+)之成分
•Enhances insulin action by boosting
insulin receptor activity (增加insulin的效
用)

61
Chromium-Deficiency
Diseases
•Not well established
•Impaired glucose tolerance

62
Outlines
• Water-Soluble Vitamin Overview
• Thiamin
• Riboflavin
• Niacin
• Pantothenic Acid
• Biotin
• Chromium (Cr)
• Vitamin B-6
• Folate
• Vitamin B-12
• Manganese (Mn)
• Molybdenum (Mo)
• Choline
• Iodine (I)
• Sulfur 63
Vitamin B-6: Pyridoxal,
Pyridoxine, Pyridoxamine
• Three compounds在體內可互相轉變
–Pyridoxal
Pyridoxal (吡哆醛)
–Pyridoxine
Pyridoxine (吡哆醇)
–Pyridoxamine
Pyridoxamine (吡哆胺) P
• Main coenzyme form:
pyridoxal phosphate (PLP)
PLP 磷酸吡哆醛

• Vitamin B-6 coenzyme required for

metabolism of amino acids
• Susceptible to destruction by heat and
other processing
64
Vitamin B-6 in Foods
• Animal sources are most bioavailable
– Meat
– Fish in muscle,
muscle in animal food
– Poultry
• Plant sources (Little in plant food)
– Whole grains (lost during refinement)
– Carrots
– Spinach
– Potatoes
– Bananas
– Avocados
– Fortified breakfast cereals (in USA)
65
66
Vitamin B-6 Needs
•Needs and upper level
–RDA
1.7mg
• Adult men: 1.7 mg

• Adult women: 1.3

1.3mg
mg
–DV: 2 mg
–Average intakes exceed RDA
–UL: 100 mg, based on development of
irreversible不可逆 nerve damage

67
Absorption, transport, storage
and excretion of Vitamin B-6
• Absorbed passively
• All three forms of B-6 are phosphorylated
in the liver
• Binds to albumin for transport in the blood
muscle tissue
• B-6 is stored in the muscle tissue
• Excess is excreted in urine

68
Functions of Vitamin B-6
1. In metabolism
a. PLP coenzyme involved in amino acid
metabolism
b. Glycogenolysis

2. Synthesis of compounds
a. Heme
b. Neurotransmitters
c. vitamins

3. In immune function and gene expression69

Functions of Vitamin B-6 -
AA metabolism
• Participates in 100+ enzymatic reactions
(involving nitrogen-containing
compounds)
• major in AA metabolism
– Transamination reaction (transaminase)
transaminase ：
可以合成 11 種 NEAA
– Decarboxylation of amino acid
(decarboxylase)
decarboxylase
– Structural rearrangement of amino acids
(racemase 消旋酶) 70
GPT: glutamic - pyruvic (acid) transaminase
GOT: glutamic - oxaloacetic (acid) transaminase

GPT

71
Functions of Vitamin B-6 -
AA metabolism
• Homocysteine metabolism
– Homocysteine同半胱胺酸
• From the metabolism of methionine
methionine

cysteine
• 形成 cysteine
• Produces toxic effect on arterial
walls 動脈壁 (atherosclerosis)
• Metabolized by vitamins
vitamins B-6B-6, B-12
B-12
folate
and folate 72
73
Functions of Vitamin B-6 -
Synthesis of compounds
• 紅血球合成
– Heme 的合成
– 幫助氧氣結合到 Heme 上

74
Functions of Vitamin B-6 -
Synthesis of compounds
• Neurotransmitter synthesis:
(decarboxylation)
–Tryptophan  serotonin
–Tyrosine  dopamine or norepinephrine
–Histidine  histamine
–Glutamic acid  gamma-aminobutyric acid
(GABA)
• Vitamin formation
–Tryptophan  niacin
75
Tryptophan → serotonin

Glutamic acid → -GABA

76
Vitamin B-6 Deficiency Diseases
• Rare
• Symptoms
小球性細胞低色素性`
– Microcytic hypochromic anemia小球性細胞低色素性
貧血 small, pale RBCs that lack sufficient
貧血:
hemoglobin and have reduced O2-carrying capacity
– Seborrheic dermatitis脂溢性皮膚炎
– Convulsions
– Depression 精神狀況
– Confusion
– Mild deficiency may lead to reduced immune
function, elevated homocysteine, and coronary
artery disease
77
Vitamin B-6 Deficiency
Diseases
• High-risk populations
–Poor diets

–Alcoholics: acetaldehyde decreases formation of

PLP and may reduce its biological activity

–Use of L-DOPA
L-DOPA for Parkinson’s disease

–Use of isoniazid (INH) for tuberculosis肺結核

isoniazid (INH)

–Use of theophylline茶鹼
theophylline茶鹼 for asthma

78
Vitamin B-6
• Pharmacological use
– Carpal tunnel syndrome腕隧道症
– PMS (no significant benefit)經前症候群
– Nausea during pregnancy

79
Outlines
• Water-Soluble Vitamin Overview
• Thiamin
• Riboflavin
• Niacin
• Pantothenic Acid
• Biotin
• Chromium (Cr)
• Vitamin B-6
• Folate
• Vitamin B-12
• Manganese (Mn)
• Molybdenum (Mo)
• Choline
• Iodine (I)
• Sulfur 80
 Folate (Folic acid, Folacin): 葉酸
• Consists of
– pteridine group蝶啶
– para-aminobenzoic acid (PABA)
– One or more molecules of
glutamic acid
• monoglutamate (folic acid) contains
one glutamate molecule
• Polyglutamates have 3 or more
glutamates; 90% of food sources

• Coenzyme form:
tetrahydrofolic acid (THFA)
四氫葉酸 81
Folate in Foods
• Liver
• Legumes
• Green leafy vegetables
• Avocados
• Oranges, orange juice, grapefruit juice
• Fortified grains and cereals
• Milk (low content, but high consumption)
• Potatoes (low content, but high
consumption)
82
83
Folate Needs
• RDA = 400
400 μμg/d
g/d for adults
• DV = 400 μg
• 懷孕婦女 600 μg/d
600 μg/d

• 哺乳婦 500
500 μg/d
μg/d

• Dietary folate equivalents (DFE) 膳食葉酸當量

– reflect differences in absorption from natural and
synthetic sources
– 1 DFE = 1 µg food folate = 0.6 µg folic acid taken
with food = 0.5 µg folic acid taken on an empty
stomach
– DFE = µg food folate + (µg of synthenic folic 84
acid
x 1.7)
Folate Needs
• UL
– 1 mg
– May mask B-12 deficiency
– Concern is with synthetic sources

85
Absorption of Folate
• Polyglutamates must be hydrolyzed by folate folate
conjugases in the absorptive cells of the GI
conjugases in the
tract to the monoglutamate form
• Monoglutamate
Monoglutamate form actively transported in
small intestine
• 食物中以多麩葉酸(polyglutamate
多麩葉酸 form)的形式存在
，因此生體利用率下降
• Synthetic form without food has nearly 100%
bioavailability
• Passively absorbed during high intake(服用補充
劑，屬單麩葉酸形式)
86
Transport, storage and
excretion of Folate
• Transport of Folate:
– Transported via portal vein to liver, converted to
polyglutamate form inside cells (traps inside cells)
– Some is released in blood and bile
• Folate in bile is reabsorbed via enterohepatic
circulation (diminished in alcoholics)
• Storage of Folate
– liver
• Excretion of Folate
– Urine
– Feces 87
Functions of Folate
1. Exchange of single carbon groups in
metabolic pathways單碳的轉移，轉移一個亞甲
基 (-CH2-)
2. Central coenzyme form: tetrahydrofolic
tetrahydrofolic
acid
acid (THFA)
(THFA)

88
Functions of Folate
3. DNA Synthesis
a. Folate supplies methylene
methylene group to uracil to form
thymine
b. Synthesis of purines (adenine and guanine)
c. Recycling of folate coenzyme requires vitamin B-12
coenzyme
d. Anticancer drug methotrexate：干擾葉酸的代謝，因此影
響DNA的合成; may require supplemental folate to
reduce toxic side effects

89
Supplying the precursors for
DNA Synthesis
•dATP, dGTP, dCTP, dTTP的合成

Trimethoprim (in bacteria)

Methotrexate(amethopterin)(Eukaryote)
90
Functions of Folate
4. Amino Acid Metabolism
– Transfers 1-carbon groups among amino acids
• Glycine  serine
• Histidine  glutamic acid
• Homocysteine  methionine (with vitamin B-12)
5. Formation of neurotransmitters;
supplementation may enhance action of
antidepressant medications
6. Maintenance of normal blood pressure
7. Reduced risk of colon cancer
91
Folate-Deficiency Diseases
• Consequences of deficiency
巨球性貧血
– Megaloblastic anemia 巨球性貧血
• Similar signs and symptoms of vitamin B-12 deficiency

– Neural tube defects 神經管缺陷

神經管缺陷

– Large, immature cells in the GI tract; decreased

absorptive capacity leads to diarrhea
– Compromised immune function due to disruption
of WBC synthesis
– Increase heart disease risk
92
Folate-Deficiency Diseases
• Susceptible populations
– Pregnant women懷孕婦女 : 600 μg/d
– Alcoholics – interferes with the enterohepatic
circulation of bile/folate

93
 Megaloblastic Anemia巨球性貧血

Cells divide
normally. Normal blood cells in the
bloodstream. The size, shape,
Folate and and color of the red blood cells
vitamin B-12
adequate show that they are normal.
Mature red blood cells have
lost their nuclei.

Red blood cell

precursor
(stem cell)

Megaloblastic blood cells

seen here in the bone marrow
Folate or are arrested at an immature
vitamin B-12 stage of development. They
deficient still have their nuclei and are
Cells are unable slightly larger than normal
to divide. red blood cells.

94
Neural Tube Defects神經管缺陷
• Maternal deficiency of folate plus genetic
predisposition
–Spina bifida:脊柱裂

–Anencephaly:無腦症

• All women capable of getting pregnant urged to

take in 400 micrograms of folic acid
• Current fortification yields about 200 micrograms of
folic acid daily

95
 Spine affected by
spina bifida
Healthy spine

Skin on back

Spinal fluid
Spinal cord

Vertebra

脊椎骨
脊椎骨包圍脊椎

96
Upper Level for Folate
• UL for synthetic folate = 1 mg/d
• Toxicity symptoms
– Epilepsy 癲癇

– Skin disorder

– Respiratory disorder

• FDA limits nonprescription supplements to 400 μg

per tablet for non-pregnant adults
• OTC非處方簽 Prenatal產前 supplement contains 800 μg
• Excess can mask vitamin B-12 deficiency
97
Outlines
• Water-Soluble Vitamin Overview
• Thiamin
• Riboflavin
• Niacin
• Pantothenic Acid
• Biotin
• Chromium (Cr)
• Vitamin B-6
• Folate
• Vitamin B-12
• Manganese (Mn)
• Molybdenum (Mo)
• Choline
• Iodine (I)
• Sulfur 98
Vitamin B-12
• Forms of Vitamin B-12
–Cyanocobalamin (free vitamin B-12):氰鈷胺素
–Methylcobalamin (coenzyme):甲鈷胺素 Two active
–5-deoxyadenosylcobalamin (coenzyme) coenzymes

• Contains cobalt
cobalt

99
Vitamin B-12 in Foods
• Synthesized by bacteria, fungi and algae
• Animal products
– meat (Organ meat: liver, kidney, heart)

– Seafood

– Eggs

– Milk

100
101
Vitamin B-12 Needs
• RDA
– 2.4 μg/d for adults and elderly adults
– Average intake exceeds RDA
• 嬰兒
– AI: 0.3 ~ 0.9 μg/d
• 懷孕
– + 0.2 μg/d
• 哺乳
– + 0.4 μg/d
• DV
– 6 μg
• No UL 102
Absorption of Vitamin B-12
1. Vitamin B-12 released from protein by HCl and
pepsin in stomach
2. Free vitamin B-12 binds to R-protein
R-protein from
salivary glands in stomach
3. In the small intestine, pancreatic protease
releases vitamin B-12 from R-protein
intrinsic factor
4. Vitamin B-12 binds to intrinsic factor made by
parietal cells in the stomach
5. Vitamin
VitaminB-12/intrinsic
B-12/intrinsic factor factor
complex complex binds
to receptor in brush border of small intestine
(ileum) for absorption
6. ~50% absorbed from dietary sources 103
Absorption of Vitamin B-12
Mouth VitB12-protein (food)

HCl + pepsin

Free Vit B12

胃 +
R protein (由唾液腺分泌)

Vit B12-R protein

小腸 trypsin

R protein + Free Vit B12 Intrinsic factor 內在因子 (胃壁細胞分泌)

吸收入迴腸刷狀細胞
血液中運輸：
Vit B12 + transcobalamin II
104
經門靜脈到肝臟
Absorption of Vitamin B-12
• Disruption of vitamin B-12 absorption
– Absence or defective synthesis of R-protein,
intrinsic factor, or pancreatic proteases
– Defective binding of vitamin B-12/intrinsic factor
complex to brush border receptor
– Absence or surgical removal of ileum or stomach
– Bacterial overgrowth of small intestine
– Tapeworm infestation 絛蟲寄生
– Anti-ulcer medications
– Chronic malabsorption syndromes
105
Transport, Storage, and
Excretion of Vitamin B-12
• Transcobalamin II binds the absorbed
vitamin B-12 and transports it through the
portal vein
• Vitamin B-12 is taken up by liver, bone
marrow, and RBCs
• 50 – 90% of body’s vitamin B-12 supply is
stored in the liver
• Excreted in bile and reabsorbed by
enterohepatic circulation
106
 Vitamin B-12
1 Salivary
gland

1
Mouth: Salivary glands produce
R-protein.

2
Stomach
a. HCl and pepsin release vitamin B-12
bound to protein in food.
b. Free vitamin B-12 binds with R-protein.
5 Liver 2 Stomach c. Parietal cells secrete intrinsic factor.

3
Small intestine
a. Trypsin from the pancreas releases
R-protein from vitamin B-12.
b. Vitamin B-12 links with intrinsic factor.

4
3 Small Ileum: Vitamin B-12/intrinsic factor
intestine complex is absorbed into blood and binds to
transport protein transcobalamin II.

4 Ileum 5
Liver: Vitamin B-12 is stored in the liver.

107
Vitamin B-12
• Functions
– Required for 2 enzymatic reactions
• Homocysteine  methionine
– Enzyme: methionine synthase
– Coenzyme: Methylcobalamin
• Enzyme needed for odd number fatty acid
metabolism
– Enzyme: methylmalonyl mutase
– Coenzyme: 5-deoxyadenosylcobalamin

108
 SAM (a methyl
Methionine donor for many
5-Me-THFA Cobalamin
cellular reactions)

Methionine
1 2 synthase

Me-Cobalamin Homocysteine
Forms folate THFA
coenzymes used
in many
reactions,
including nucleic
acid synthesis

109
Vitamin B-12-Deficiency Diseases

• Looks like folate deficiency

• Consequences
– Pernicious (“leading to death”) anemia惡性
惡性

貧血can result from inadequate production

貧血
of intrinsic factor
intrinsic factor
– Macrocytic (megaloblastic) Anemia巨球性貧
血
• Identical to anemia from folate deficiency
• Due to disruption of normal DNA and RBC
synthesis 110
Vitamin B-12-Deficiency Diseases
• Looks like folate deficiency
• Consequences
– Neurological Changes
• Paresthesia感覺異常: burning, tingling麻 ,
prickling刺痛, and numbness麻痺in the legs
• Mental problems: loss of concentration and
memory, disorientation, dementia
• Neurological complications often precede
development of anemia
– Elevated Plasma Homocysteine
Concentrations
111
• Risk factor for heart attack and stroke
Vitamin B-12-Deficiency Diseases
• Susceptible populations
– Older adults
• Atrophic gastritis
– decreases HCl and digestive enzymes secretion
– Achlorhydria(胃酸缺乏)
– Synthetic vitamin B-12 (crystalline form) is readily absorbed without R-protein
and intrinsic factor

Vegetarians
– Vegetarians
• Infants of vegan mothers
• Vegans (after many years)
– People with malabsorptive diseases
• Treatment
– Monthly injections
– Nasal gel 噴鼻凝膠
– Oral doses (1-2 mg)
112
• Passive diffusion
Outlines
• Water-Soluble Vitamin Overview
• Thiamin
• Riboflavin
• Niacin
• Pantothenic Acid
• Biotin
• Chromium (Cr)
• Vitamin B-6
• Folate
• Vitamin B-12
• Manganese (Mn)
• Molybdenum (Mo)
• Choline
• Iodine (I)
• Sulfur 113
Manganese (Mn)
•Foods
–Whole-grain cereals, nuts, legumes, leafy green
and tea
•Needs
–AI 2.3 mg/daily adult men 1.8 mg/daily adult
women
–DV 2 mg/daily
–Average intake meets AI
•UL = 11 mg/d

114
115
Absorption and Transport of
Manganese
• Simple diffusion and active transport in the small
intestine
• Absorption efficiency is ~10%, affected by dietary
intake and iron status
– High absorption efficiency with low manganese intake and
adequate iron status
• Decreased absorption with high intakes of
manganese and possibly calcium, iron, and
phytates
• Transport of Manganese
– bound to transferrin and alpha-2-macroglobulin for
transport to liver and other tissues
116
Manganese；Mn 錳
• Cofactor for enzymes (pyruvate
carboxylase, superoxidase dismutase)
– Antioxidant defense (Mn superoxide dismutase)
• Role in bone formation
– collagen formation

117
Outlines
• Water-Soluble Vitamin Overview
• Thiamin
• Riboflavin
• Niacin
• Pantothenic Acid
• Biotin
• Chromium (Cr)
• Vitamin B-6
• Folate
• Vitamin B-12
• Manganese (Mn)
• Molybdenum (Mo)
• Choline
• Iodine (I)
• Sulfur 118
Molybdenum；Mo 鉬
•High intake will inhibit copper absorption
•Required by several enzymes (xanthine
dehydrogenase 黃嘌呤脫氫酶； xanthine oxidase
黃嘌呤氧化酶) – enzyme cofactor
•Deficiency rare
–Increased heart and respiration rates
–Night blindness, mental confusion
–Edema, weakness, coma
•RDA = 45 μg/d, DV: 75 μg
•Toxicity seen in animals
•UL = 2 mg/d
119
Outlines
• Water-Soluble Vitamin Overview
• Thiamin
• Riboflavin
• Niacin
• Pantothenic Acid
• Biotin
• Chromium (Cr)
• Vitamin B-6
• Folate
• Vitamin B-12
• Manganese (Mn)
• Molybdenum (Mo)
• Choline
• Iodine (I)
• Sulfur 120
Choline 膽鹼
• Not yet considered a B-vitamin
• No coenzyme form
• High concentrations in the body
• Composed of phospholipids, such as
phosphatidylcholine (lecithin卵磷脂)

121
Choline in Foods
• Widely distributed (phospholipid form in
cellular membrane)
• Milk
• Liver
• Eggs
• Peanuts
• Lecithins added to food

122
Choline Needs
• AI
– 550 mg/d for adult males
– 425 mg/d for adult females
• UL
– 3.5 grams
• Can be synthesized by the body
• Normal consumption is ~700-1000 mg/d

123
124
Absorption, Transport, Storage,
and Excretion of Choline
• Absorbed from the small intestine via
transport proteins
• All tissues contain choline
• Some choline is excreted in urine
• Excess choline is converted to betaine
甜菜鹼

125
Functions of Choline
• Precursor for acetylcholine
(neurotransmitter)
• Precursor for phospholipids (such as
lecithin)
• Precursor for the betaine甜菜鹼 (methyl
donor)
– Assist in the conversion of homocysteine to
methionine

126
Outlines
• Water-Soluble Vitamin Overview
• Thiamin
• Riboflavin
• Niacin
• Pantothenic Acid
• Biotin
• Chromium (Cr)
• Vitamin B-6
• Folate
• Vitamin B-12
• Manganese (Mn)
• Molybdenum (Mo)
• Choline
• Iodine (I)
• Sulfur 127
Iodide in Foods
•Iodized salt (1/2 tsp. meets RDA for iodide)加碘
的鹽
•Saltwater fish, seafood 海產
•Sea salt is a poor source (loss during processing)
•Plant source dependent on soil content
•Goitrogens 致甲狀腺腫物質(in some raw
vegetables) decrease bioavailability of iodine and
inhibit use by thyroid gland
–Raw turnips 蕪菁
–Rutabagas 蕪菁甘藍
–Cauliflower 白花椰菜
–Broccoli 綠花椰 128
129
Iodide Needs
•RDA = 150 μg/d
•RDA = 140 μg/d in Taiwan
•Average intake exceeds RDA (190-300 μg)
•DV = 150 μg

130
Absorption, Transport, Storage,
and Excretion of Iodide
•Absorbed in inorganic form along the GI tract (小
腸吸收)
•Transported free or bound to proteins (thyroid-
binding globulin and albumin) in the blood (血
漿運送)
•~75% of body stores are in thyroid gland (以
thyroglobulin 的形式儲存，for thyroid hormone
synthesis )
•Excreted via kidneys

131
 Functions of Iodide
•Thyroid hormone synthesis (from iodide and
tyrosine)
–Metabolic rate
–Growth
–Development

132
 Functions of Iodide
•Action of thyroid hormones
–Synthesis of T4 (thyroxine, prehormone) in
response to TSH (thyroid-stimulating hormone)
secretion
–T4 (thyroxine) is converted to T3 (triiodothyronine ,
active hormone) by deiodinase
–T3 regulates basal metabolic rate, production of
body heat energy, human growth.

133
Iodide-Deficiency Diseases
•Causes
–Low intake (from low soil content)
–Consumption of goitrogens 致甲狀腺腫物質
•Consequences of deficiency [(Iodine
Deficiency Disorders (IDD)]
–Insufficient T4 (continual release of TSH)
–Growth of the thyroid gland (goiter甲狀腺腫大)
–Drop in the metabolic rate
–Harmful during pregnancy
–Cretinism呆小症 (生長遲緩、心智發展障礙)
134
Goiter 甲狀腺腫大

• 壓迫氣管造成
呼吸困難
– 碘治療
135
– 手術
Upper Level for Iodide
•Thyroid hormone synthesis is inhibited
•Consumption of seaweed海藻
•UL = 1.1 mg/d

136
137
Outlines
• Water-Soluble Vitamin Overview
• Thiamin
• Riboflavin
• Niacin
• Pantothenic Acid
• Biotin
• Chromium (Cr)
• Vitamin B-6
• Folate
• Vitamin B-12
• Manganese (Mn)
• Molybdenum (Mo)
• Choline
• Iodine (I)
• Sulfur 138
Sulfur
•Needs
–No AI or UL set
•Function
–Synthesis of sulfur containing compounds
–Stabilize the structure of protein
–Participates in acid-base balance
•No deficiency or toxicity

139