Transcript Amino group needs to be excreted

Chapter 10: The WaterSoluble Vitamins
Overview of Water-Soluble
Vitamins





Dissolve in water
Easily destroyed or washed out during food
storage and preparation.
Are easily absorbed and excreted
Not stored in the body tissues and must be
replaced each day.
Seldom reach toxic levels
Overview of Water-Soluble Vitamins

Many B-complex vitamins needed for energy
metabolism and form an integral part of coenzymes

Help the body metabolize CHO, lipids and
amino acids



Thiamin pyrophosphate – TPP (thiamin)
Flavin Adenine Dinucleotide (FAD), Flavin Mononucleotide
(FMN)(riboflavin)
Nicotinamide Adenine Dinucleotide (NAD), Nicotinamide
adenine dinucleotide phosphate (NADP)(niacin)

Coenzyme A (pantothenic acid)

Pyridoxal phosphate (PLP) (Vitamin B-6)

Tetrahydrofolic acid (folate)
Enrichment Act of 1941 and 1998
Many nutrients lost through milling process of
grains
 Grain/cereal products are enriched with

Thiamin, riboflavin, niacin, folate, iron
 Enriched grains still deficient in B-6, magnesium
and zinc


Whole grains contain original nutrients
Distinction between water-soluble and
fat-soluble vitamins
Fat-soluble vitamins
Water-soluble vitamins
Absorption Lymph first, then the blood
Transport
Direct absorption into
the blood
Protein carriers used by many Freely transported
Requireme Periodic doses required
nts
Storage
Stored in cells associated with
fat
Frequent doses
required
Circulate in waterfilled parts of the body
Excretion
Less readily excreted, tend to
remain in fat-storage sites
Toxic levels likely when
consuming supplements
Excreted in urine by
kidneys
Toxic levels possible
when consuming
Toxicity
Thiamin

Functions as a coenzyme: Thiamin pyrophosphate
(TPP)



In metabolism of CHO; & amino acids
Decarboxylation of alpha keto acids (page 227)
Enzyme is Transketolase: coverts glucose to a 5carbon sugar
Food Sources of Thiamin



Wide variety of food
White bread, pork, hot dogs, luncheon meat,
cold cereal
Enriched grains/ whole grains
RDA For Thiamin




1.1 mg/day for women
1.2 mg/day for men
Most exceed RDA in diet
Surplus is rapidly lost in urine; non toxic
Deficiency of Thiamin

Beriberi


first observed in the Far East where polished rice
replaced rice where bran remained intact.
characterized by
loss of sensation in the hands and feet, muscular
weakness, advancing paralysis,and abnormal heart
action.
 Peripheral neuropathy


Dry beriberi


Weakness, nerve degeneration, irritability, poor
arm/leg coordination, loss of nerve transmission
Wet beriberi

Edema, enlarge heart, heart failure
Wenicke-Koisakoff Syndrome

Mainly in alcoholics
Alcohol diminishes thiamin absorption
 Alcohol increases thiamin excretion
 Poor quality diet

Involuntary eye movement; double vision
 Ataxia: staggering, poor muscle
coordination
 Mental confusion, “drunken stupor”

Riboflavin

Coenzymes:
Flavin mononucleotide (FMN)
 Flavin adenine dinucleotide (FAD)

Oxidation-reduction reactions
 Electron transport chain
 Citric Acid Cycle
 Catabolism of fatty acids: beta oxidation
 FMN shuttles hydrogen ions and electrons to
into the electron transport chain

Food Sources of Riboflavin







Milk/products
Enriched grains
Liver
Oyster
Brewer’s yeast
Sensitive to uv radiation (sunlight)
Stored in paper, opaque plastic containers
RDA for Riboflavin




1.1 mg/day for women
1.3 mg/day for men
Average intake is above RDA
Toxicity not documented
Deficiency of Riboflavin

Ariboflavinosis

Glossitis, cheilosis, seborrheic dermatitis,
stomatitis, eye disorder, throat disorder,
nervous system disorder
Niacin



Nicotinic acid (niacin) & nicotinamide
(niacinamide)
Coenzyme
 Nicotinamide adenine dinucleotide (NAD)
 Nicotinamide adenine dinucleotide phosphate
(NADP)
Oxidation-reduction reaction
Food Sources of Niacin



Mushroom
Enriched grains
Beef, chicken, turkey, fish, eggs,milk




Amino acid tryptophan can be converted to niacin
Heat stable; little cooking loss
60mg tryptophan can be converted into 1 mg
niacin
Estimate by dividing the total gram of protein by
6
Deficiency of Niacin

Pellagra
 3 Ds: Dermatitis, dementia, diarrhea

appeared in Europe in early 1700s when corn
became staple food

corn lacks niacin and tryptophan
Niacin as a Medicine



75-100 x RDA can lower LDL and increase HDL
Slow/ reverse progression of atherosclerosis
with diet and exercise
Toxicity effects

Flushing of skin, itching, nausea, liver damage
Content Review





How are water-soluble vitamins different from fatsoluble vitamins?
Many of the B vitamins all function as a coenzyme,
what is a coenzyme?
What disease is associated with a deficiency of
niacin?
What disease is associated with a deficiency of
thiamin?
What is the Enrichment Act? What nutrients are
involved?
Pantothenic Acid
Part of Coenzyme-A
 Essential for metabolism of CHO, fat,
protein

Glucose
Fatty acids
Acetyl-CoA
Alcohol
Amino Acids
Food Sources of Pantothenic
Acid







Meat
Milk
Mushroom
Liver
Peanut
Adequate Intake = 5 mg/day
Average intake meets AI
Biotin
Free and bound form
 Biocytin (protein bound form)

Freed by Biotinidase in small intestine
 Infant with genetic defect : low levels of
biotinidase

Metabolism of CHO, fat, protein (C
skeleton)
 DNA synthesis

Functions of Biotin




Required to convert pyruvate to oxaloacetate
(TCA cycle) and thus ATP production.
Required for fatty acid synthesis
Breaks down leucine
Sources



Widely distributed in foods and is produced by
intestinal bacteria
Liver, egg yolk , whole grains, cauliflower are good
food sources
Avidin in raw egg whites bind biotin
Biotin Needs



Adequate Intake is 30 ug/day for adults
This may overestimate the amount
needed for adults
No Upper Limit for biotin
Biotin Deficiency






Rare
High intake of raw egg white diet
Alcoholics
Biotinidase deficiency
Anticonvulsant drug use
Signs & symptoms: skin rash, hair loss,
convulsion, neurological disorders, impaired
growth in children
Vitamin B-6 family: Pyridoxal,
Pyridoxine, Pyridoxamine





Main coenzyme form: pyridoxal phosphate
(PLP)
Activate enzymes needed for metabolism of
CHO, fat , protein
Transamination
Synthesis of hemoglobin and oxygen binding
and white blood cells
Synthesis of neurotransmitters
Functions of Vitamin B-6









Participates in 100+ enzymatic reactions
Decarboxylation of amino acid (decarboxylase)
Transamination reaction (transaminase)
Structural rearrangement of amino acids (racemase)
Heme synthesis
CHO metabolism
Lipid metabolism
Neurotransmitter Synthesis
Conversion of tryptophan to niacin
Other Role of Vitamin B-6
Homocysteine
 From the metabolism of methionine
 Produces toxic effect on arterial walls
(atherosclerosis)
 Metabolized by vitamins B-6, B-12 and folate
Food Sources of Vitamin B-6







Meat, fish, poultry
Whole grains (not enriched back)
Banana
Spinach
Avocado
Potato
Heat and alkaline sensitive
RDA for Vitamin B-6



1.3 - 1.7 mg/day for adults
Daily Value set at 2 mg
Average intake is more than the RDA
Deficiency of Vitamin B-6
Microcytic hypochromic anemia
 Seborrheic dermatitis
 Convulsion, depression, confusion
 Reduced immune response
 Peripheral nerve damage

Factors That Affect B-6
Requirement
Alcohol reduces PLP formation
L-DOPA-medication used to treat
Parkinson’s disease and
Isoniazid-antituberculosis medication
 Reduce blood concentration of PLP
 Need extra vitamin B-6
B-6 As A Medicine?

PMS






B-6 to increase the level of serotonin
Improve depression
Not a reliable treatment
Toxicity potential
Can lead to irreversible nerve damage
with > 200 mg/day
Upper level set at 100 mg/day
Folate (Folic acid, Folacin)




Consists of pteridine group, para-aminobenzoic
acid (PABA), and glutamic acid
Coenzyme form: tetrahydorfolic acid (THFA)
Produce many identical deficiency signs and
symptoms as vitamin B-12
Vitamin B-12 is needed to recycle folate
coenzyme
Absorption, Metabolism of Folate






Absorbed in the monoglutamate form with the
help of folate conjugase
Actively absorbed during low to moderate intake
Passively absorbed during high intake
Delivered to the liver where it is changed back to
the polyglutamate form
Mostly stored in the liver
Excreted in the urine and bile (enterohepatic circulation)
Functions of Folate

DNA synthesis






Transfer of single carbon units
Synthesis of adenine and guanine
Anticancer drug methotrexate
Homocysteine metabolism
Neurotransmitter formation
Amino acid metabolism
Food Sources of Folate





Liver
Fortified breakfast cereals
Grains, legumes
Foliage vegetables
Susceptible to heat, oxidation, ultraviolet
light
RDA for Folate



400 ug/day for adults
Daily Value is set at 400 ug
Dietary folate equivalents (DFE)


are units to express folate needs throughout
life except during child bearing years
DFE = [(total synthetic folate) x 1.7] + total
food folate intake
Deficiency of Folate



Similar signs and symptoms of vitamin B12 deficiency
Pregnant women
Alcoholics

Interferes with the enterohepatic circulation of
bile/folate
Megaloblastic Anemia
Neural Tube Defects



Spina bifida
Anencephaly
Importance of folate
before and during
pregnancy
Toxicity of Folate






Epilepsy
Skin, respiratory disorder
FDA limits nonprescription supplements to
400 ug per tablet for non-pregnant adults
OTC Prenatal supplement contains 800 ug
Upper Level for synthetic folate is 1 mg
Excess can mask vitamin B-12 deficiency
Vitamin B-12
Cyanocobalamin, methlcobalamin,
5-deoxyadenosylcobalamin
 Contains cobalt
 Folate metabolism
 Synthesized exclusively by bacteria, fungi, and
algae
 Maintenance of the myelin sheaths
 Rearrange 3-carbon chain fatty acids so can
enter the Citric Acid Cycle

Absorption of Vitamin B-12
Therapy for Ineffective Absorption




Many factors can disrupt this process
Monthly injections of vitamin B-12
Vitamin B-12 nasal gel
Megadoses of vitamin B-12 to allow for
passive diffusion
Food Sources of Vitamin B-12








Synthesized by bacteria, fungi and algae
(Stored primarily in the liver)
Animal products
Organ meat
Seafood
Eggs
Hot dogs
Milk
RDA for Vitamin B-12
2.4 ug/ day for adults and elderly
adults
 Average intake exceeds RDA
 B-12 stored in the liver; little is lost
 Non-toxic

Functions of Vitamin B-12



Helps convert methylmalonyl CoA to
succinyl CoA (citric acid cycle)
Recycles folate coenzymes
Nerve functions


Maintains myelin sheath
Megalobalstic anemia
Deficiency of Vitamin B-12



Pernicious anemia
 Nerve degeneration, weakness
 Tingling/numbness in the extremities
(parasthesia)
 Paralysis and death
 Looks like folate deficiency
Usually due to decreased absorption ability
Achlorhydria, especially in elderly
Homocysteine and the B Vitamins
Choline
Absorbed from the small intestine
 All tissues contain choline
 Excess choline is converted to
betaine

Functions of Choline





Precursor for acetylecholine (neurotransmitter)
Precursor for phospholipids (such as lecithin)
Involved in the export of VLDL from the liver
Precursor for the methyl donor betaine
Assist in the conversion of homocysteine to
methionine
Food Sources of Choline







Widely distributed
Milk
Liver
Eggs
Peanuts
Lecithins added to food
Deficiency rare
Needs for Choline





Adequate Intake is 550 mg/day for adult
males
Adequate Intake is 425 mg/day for adult
females
Normal consumption is ~700-1000 mg/day
High doses associated with fishy body odor,
vomiting, salivation, sweating, hypotension,
GI effects
Upper Level is set at 3.5 g/day (3500 mg/day)
Deficiency of Choline


Decrease choline stores
Liver damage (fatty livers)
Vitamin C






Ascorbic acid (reduced form), dehydroascorbic
acid (oxidized form)
Synthesized by most animals (not by human)
Absorbed by a specific energy dependant
transport system
Passive transport if intake is high
Decrease absorption with high intakes
Excess excreted
Functions of Vitamin C






Reducing agent (antioxidant)
Iron absorption
Synthesis of carnitine, tryptophan to serotonin,
thyroxine, cortiscosteroids, aldosterone,
cholesterol to bile acids
Immune functions
Synthesis of other compounds
Questionable as to vitamin C’s role as an
antioxidant in people
Collagen Synthesis
Food Sources of Vitamin C








Citrus fruits
Potatoes
Green peppers
Cauliflower
Broccoli
Strawberries
Romaine lettuce
Spinach



Easily lost through
cooking
Sensitive to heat
Sensitive to iron,
copper, oxygen
RDA for Vitamin C







90 mg/day for male adults
75 mg/day for female adults
+35 mg/day for smokers
Average intake ~72 mg/day
Fairly nontoxic (at <1 gm)
Upper level is 2 gm/day
Excess intake will not cure the common cold
Deficiency of Vitamin C

Scurvy




Deficient for 20-40 days
Fatigue, pinpoint hemorrhages
Bleeding gums and joints, hemorrhages
Associated with poverty
Vitamin-Like Compounds





Carnitine
Inositol
Taurine
Lipoic acid
Synthesized in the body at the expense of
amino acids and other nutrients
Carnitine




Found in meat and dairy products
Synthesized in the liver from amino acids
lysine and methionine
Transports fatty acids into the
mitochondria
Aids in the removal of excess organic
acids
Inositol






Myo-inositol
Found in animal products
Synthesized from glucose
Precursors to eicosanoids
Metabolizes calcium ions
Metabolism is altered in people with
diabetics, multiple sclerosis, kidney failure,
certain cancers
Taurine





Found only in animal products
Synthesized from methionine and cysteine
Associated with the photoreceptor in the eye
Antioxidant activity in the white blood cell and
pulmonary tissue
CNS function, platelet aggregation, cardiac
contraction, insulin action, cell differentiation and
growth
Lipoic Acid




Found in meats, liver, and yeast
Redox agent
Needed in reactions in which CO2 is lost
from a substrate
Regenerates vitamin C and glutathione
Bogus “Vitamins”

Para-aminobenzoic acid (PABA)



Laetrile



“Vitamin B-17”
Contains cyanide, promoted as a cancer cure
Bioflavonoids


Part of folate, but not able to make folate
A part of a B-complex family for bacteria
“Vitamin P” --no nutritional requirement
Pangamic Acid

“Vitamin B-15” and is illegal
Cancer


Many diseases
Formation of tumors (neoplasms)


Benign
Malignant
Types of Cancers

Carcinomas


Sarcomas


Connective tissues and bones
Leukemias


Cells that covers the body, including the secretory
organs
Blood forming tissues
Lymphomas

Lymph nodes or lymphoid tissues
Cancer Deaths
Carcinogenesis

Protooncogenes


Tumor Suppressor Genes



Genes that prevent cells from dividing
P53 gene finds error on the DNA and repairs it
Oncogene



Genes that cause a resting cell to divide
The cancer gene
A protoonocogene out of control
DNA Repair Mechanism
Cell Replication

Telomeres


Telomerase




Caps at the ends of chromosomes
Enzyme that maintains the length and completeness
Daughter cells are slightly shorter and telomerase
activity decreases
Cell undergoes apoptosis
Malignant tumor cells, the telomerase activity
increases—the cells can live indefinitely
Cancer Initiation, Promotion, and
Progression
Cytochrome P-450
 Prevents
cancer initiation
 In the liver and intestinal cells
 Converts dangerous
compounds into harmless
water-soluble metabolites
Cancer Initiation
 Exposure
to carcinogen
 Alteration of DNA
 Is relatively short
Cancer Promotion



May last for months or years
Damage is “locked” in
Cell division increases


Promoters: estrogen, alcohol, maybe dietary
fat
Decrease time available for repair
Cancer Progression






Final stage
Cancer cells proliferate and form a mass
Invade surrounding tissue
Metastasize to other tissues
Heredity can only explain a small
percentage of cancers
Environment contributes to most cancer
Role of Diet








Excessive intake of calories increases the risk
of cancer
Excessive body fat affects sex hormone
production
High intake of fruits and vegetables is
associated with lower risk
High intake of meats and protein is
associated with higher risk
Excessive alcohol increases the risk
Excessive charcoal broiling increases risk
Nitrosamines (from nitrite) increases risk
Mycotoxins (from fungi) increases risk
Fat and Cancer




The National Academy of Sciences
recommends 30% of total calories from
fat
Effects of the type of fat to cancer
There are still wide gaps in knowledge
linking fat and cancer
Excessive intake is a more likely cause
Calcium,Vitamin D and Cancer




Calcium intake is inversely related to
cancer
Calcium binds to bile acids in the colon
Vitamin D inhibits progression of
cancerous polyps
Vitamin D inhibits rapid colon/rectal cell
growth in patients with ulcerative colitis
Recommendations to Reduce the
Risk for Cancer







Remain physically active
Avoid obesity
Engage in physical training that promotes lean
muscle mass
Consume abundance of fruits and vegetables
Consume plenty of low-fat/nonfat dairy products
Avoid high intakes of red meat and animal fat
Avoid excessive alcohol
Warning Signs (CAUTION)









Early detection is critical
Unexplained weight loss
A change in bowel or bladder habits
A sore that does not heal
Unusual bleeding or discharge
A thickening or lump in the breast or elsewhere
Indigestion or difficulty in swallowing
An obvious change in a wart or a mole
A nagging cough or hoarseness