Amino group needs to be excreted

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Chapter 10: The Water-

Soluble 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 )

 Cofactor ( biotin )

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

Transport

Lymph first, then the blood Direct absorption into the blood

Protein carriers used by many Freely transported

Requireme nts

Periodic doses required

Storage

Excretion

Toxicity

Stored in cells associated with fat

Less readily excreted, tend to remain in fat-storage sites

Toxic levels likely when consuming supplements

Frequent doses required

Circulate in waterfilled parts of the body

Excreted in urine by kidneys

Toxic levels possible when consuming supplements

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 AcetylCoA

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 B-

12 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 CO

2 is lost from a substrate

 Regenerates vitamin C and glutathione

Bogus “Vitamins”

Para-aminobenzoic acid (PABA)

Part of folate, but not able to make folate

A part of a B-complex family for bacteria

Laetrile

“Vitamin B-17”

 Contains cyanide, promoted as a cancer cure

Bioflavonoids

“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

 Cells that covers the body, including the secretory organs

Sarcomas

 Connective tissues and bones

Leukemias

 Blood forming tissues

Lymphomas

 Lymph nodes or lymphoid tissues

Cancer Deaths

Carcinogenesis

Protooncogenes

 Genes that cause a resting cell to divide

Tumor Suppressor Genes

Genes that prevent cells from dividing

P53 gene finds error on the DNA and repairs it

Oncogene

 The cancer gene

 A protoonocogene out of control

DNA Repair Mechanism

Cell Replication

 Telomeres

 Caps at the ends of chromosomes

 Telomerase

 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 c hange in bowel or bladder habits

A sore that does not heal

U nusual bleeding or discharge

A t hickening or lump in the breast or elsewhere

I ndigestion or difficulty in swallowing

An o bvious change in a wart or a mole

A n agging cough or hoarseness

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