NHM 361 - MOD 6

list the water soluble vitamins

vitamin C

B1

B2

B3

B5

B6

B7

B9

B12

what are vitamins? and what are their classifications?

vitamins are organic micronutrients

classifications: water soluble and fat soluble

what is vitamin C also known as?

absorbic acid

can humans synthesize vitamin C? why or why not? and how do they get it if not?

no

genetic mutation over 61 million years ago that disabled humans to synthesize glucose into vitamin C

acquiring vitamin C is essential through diet and sun exposure

what is the main food source for vitamin C?

abundant in fruits and veggies

name the four functions of vitamin C

• supports collagen synthesis

• supports neurotransmitter synthesis

• acts as an antioxidant

• enhances iron absorption

how does vitamin C support collagen synthesis?

vitamin C supports prolyl hydroxylase and lysyl hydroxylase

both of these enzymes are required during collagen synthesis

how does vitamin C support neurotransmitter synthesis?

vitamin C supports dopamine hydroxylase, an enzyme that synthesizes norepinephrine

how does vitamin C act as an antioxidant

vitamin C donates an electron reducing harmful oxidants

basically, vitamin C is willing to sacrifice one of its own electrons to neutralize a reactive oxidant (like a free radical). this donation stabilizes the oxidant and stops a chain reaction of cellular damage

how does vitamin C enhances iron absorption?

vitamin C reduces non-heme iron increasing iron absorption

what is scurvy?

scurvy is a disease that results from vitamin C deficiency and malfunction of vitamin C-dependent enzymes

symptoms include bleeding, poor wound healing, depression

name the coenzymes from B vitamins that are involved in energy metabolism

• thiamin (B1)

• riboflavin (B2)

• niacin (B3)

• pantothenic acid (B5)

• pyridoxine (B6)

• biotin (B7)

• folate (B8)

• cobalamin (B12)

what is the structure of thiamin?

thiamin is vitamin B1

its structure contains 2 ring structures (pyrimidine and thiazole) with one hydroxyl group

what are the various forms of thiamin?

thiamin monophosphate (TMP)

thiamin diphosphate (TDP) → also called thiamin pyrophosphate (TPP) which is the most active form

thiamin triphosphate (TTP)

name the food sources of vitamin B1

meat

eggs

legumes

nuts

enriched and whole grain products

what is the main function of thiamin?

vitamin B1(thiamin) assists with function of pyruvate dehydrogenase complex that converts pyruvate into acetyl-CoA

THIS IS VERY IMPORTANT FOR CARBOHYDRATE METABOLISM

what is beriberi? and what are the two kinds?

a disease caused by the overall lack or malabsorption of thiamin

most common where polished rice is a food staple

wet beriberi: abnormalities of the cardiovascular system (ex: swelling and HBP)

dry beriberi: abnormalities of the nervous system (ex: mental confusion, poor coordination, obtundation

explain why polished rice can cause a thiamin deficiency

thiamin is found mostly in the outer layer of the grain and in the germ which are removed during the refining process

what is riboflavin a precursos of?

riboflavin (vitamin B2) is a precursor of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN)

both FAD and FMN act as electron carriers in the ETC chain to produce ATP

FAD is required for fatty acid oxidation

food sources for riboflavin

dairy products

fish

poultry

meat

eggs

leafy green veggies

enriched grain products

what is niacin a precursor of?

niacin is a precursor of

• NAD+/NADH

• NADP+/NADPH

which amino acid can be converted to niacin?

tryptophan

food sources for niacin?

fish

meats

enriched grain products

legumes

what are the two main functions of niacin?

1. NAD+/NADH

   1. exists as two forms, an oxidized form (NAD+) and a reduced form (NADH) and is involved in hundreds of oxidation-reduction reactions

2. NADP+/NADPH

   1. exists as an oxidized from (NADP+) and a reduced from (NADPH)

   2. involved in biosynthesis of fatty acids, cholesterol, and glutathione

when talking about the function of niacin, one of its functions is how the oxidized and reduced form are involved in hundreds of oxidation-reduction reactions. list those reactions:

1. glycolysis

2. TCA cycle

3. ETC

4. beta-oxidation

5. alcohol metabolism

what is pellagra and what are its symptoms

a disease caused by niacin deficiency

symptoms:

• dermatitis

• diarrhea

• dementia

• death

what is pantothenic acid a precursor for?

pantothenic acid (vitamin B5) is a precursor for coenzyme A which is a part of acetyl-CoA

what are food sources for pantothenic acid?

widespread in a variety of foods like algae, plants, animals

what are the 6 major forms of vitamin B6?

1. pyridoxal (PL)

2. Pyridoxine (PN)

3. Pyridozamine (PM)

4. Pyridoxal 5 phosphate (PLP)

5. Pyridoxine 5 phosphate (PNP)

6. Pyridoxamine 5 phosphate (PMP)

what are food sources of vitamin B6?

meats

whole grains

vegetables

fruits

explain the main function of vitamin B6

pyridoxal 5 phosphate (PLP) serves as a coenzyme for more than 100 enzymes:

1. transamination

2. decarboxylation

   1. neurotransmitter synthesis often requires decarboxylation

3. heme synthesis

4. homocysteine metabolism

name and describe the two major vitamin B6 deficiencies

1. microcytic anemia

   1. due to reduction of hemoglobin synthesis (small size of RBCs)

2. neurological disorder

   1. decarboxylases are involved in synthesis of neurotransmitters (e.g. GABA and dopamine), therefore lack of its coenzyme (PLP) leads to altered brain function

biotin acts as a coenzyme for what?

vitamin B7 (biotin) acts as a coenzyme for various carboxylases (therefore, regulates carboxylation), which are involved in macronutrient metabolism

1. acetyl-CoA carboxylase (acetyl-CoA → maolnyl-CoA) in fatty acid synthesis

2. pyruvate carboxylase (pyruvate → oxaloacetate) in gluconeogenesis

food sources for biotin

liver

soybeans

egg yolk

can mammals synthesize biotin?

no, but intestinal bacteria can, so deficiencies in biotin are rare

discuss the structure of folate

folate (vitamin B9) contains

• pteridine ring

• para aminobenzoic acid (PABA)

• one or more glutamate residues

food sources of folate

leafy greens

citrus fruits

dried beans

what is the function of folate-1

• Folate is a precursor for the coenzyme tetrahydrofolate (THF)

• THF is involved in 1-carbon unit transfers as a donor or an acceptor of one carbon

• Folate supports purine and pyrimidine synthesis

• Folate also regulates amino acid and choline metabolism

  • E.g. methionine metabolism

what is the function of folate-2

• Homocysteine can be converted to methionine

  • This reaction requires folate (B9) and cobalamin (B12)

• Homocysteine also can be converted to cysteine

• This reaction requires PLP (B6)

• High blood levels of homocysteine are correlated with enhanced risk of cardiovascular disease (e.g. thrombosis)

• This mechanism is not fully understood

what are the two main deficiencies for anemia? describe them.

Megaloblastic anemia

• Characterized by enlarged and fragile red blood cells that are prone to apoptosis (cell death, cellular “suicide”)

• Folate and cobalamin (B12) deficiency can impair DNA synthesis and cell division of RBCs. this leads to continuing cellular growth without division

Neural tube defect

• Adequate dietary folate is important for the rapidly dividing embryonic neural tube

• Inadequate folate during pregnancy leads to a group of birth defects called neural tube defects

• Congenital malformations of the brain and spinal cord caused by the failure of the neural tube to close during early embryogenesis

• Good folate status early in pregnancy reduces risk → one of the prenatal vitamins 

what is the structure of cobalamin?

vitamin B12 (cobalamin) contains cobalt atom surrounded by a heme-like ring (corrin ring)

cobalamin exists as multiple forms:

• Hydroxocobalamin with -OH group

• Methylcobalamin with -CH3 group

food sources of cobalamin

animal products like meat, eggs, dairy

fortified foods

what are the two main functions of cobalamin?

• supports conversion of homocysteine to methionine

• supports oxidation of odd-numbered fatty acids

discuss cobalamin metabolism in the stomach and in the small intestine

In the stomach:

• Intrinsic factor (produced by parietal cells) binds to vitamin B12

In small intestine:

• Vitamin B12-intrinsic factor complex binds to receptor, and it is internalized by endocytosis

talk about the deficiency of vitamin B12

DEFICIENCY OF VITAMIN B12

• Megaloblastic anemia

  • Deficiency of vitamin B12 impairs DNA synthesis and leads to failure of proper RBC development

• Abnormalities in brain and nervous system

  • Accumulation of metabolites of odd-numbered fatty acids can cause neurotoxicity

• High risk for cardiovascular diseases

  • Accumulation of homocysteine is correlated with CVD risk

• Risk population

  • Vegans, older adults, and gastric bypass patients

list the fat soluble vitamins

vitamins D, E, K, A

vitamin A exists as multiple forms. Name themL

retinol (alcohol form)

retinal = retinaldehyde (aldehyde form)

retinoic acid (acid form)

retinyl esters (ester form, storage form)

name and describe the two main types of vitamin A that is received from diet

retinyl esters: major form of vitamin A in the diet. found in liver, milk, eggs, fish oil

beta-carotene: called provitamin A because it is converted to vitamin A (retinal and retinol) during digestion and absorption

what foods is beta-carotene found in?

yellow and orange-colored fruits and vegetables

what are the functions of Vitamin A-1?

• 11-cis-retinal regulates vision!!!

• rhodopsin: a receptor found in the retina

describe what rhodopsin is composed of and what happens to it during the functioning of vitamin A-1

rhodopsin is a receptor found in the retina

it is composed of 11-cis-retinal and opsin

when bright light stimulates rhodopsin, 11-cis-retinal is converted to all-trans retinal, and is dissociated from rhodopsin (inactivated)

when all-trans-retinal is converted back to 11-cis-retinal, rhodopsin can be reformed and activated

what are the functions of vitamin A-2

retinoic acids regulate gene expression

all-trans retinoic acid binds to retinoic acid receptors (RAR) and 9-cis retinoic acid binds to retinoid X receptors (RXR)

binding of vitamin to the nuclear receptors enhances the transcription of selected genes

what are the functions of vitamin A-3

carotenoids function as antioxidants

carotenoids can react with and quench free radicals - especially valuable in the protection of cell membranes

what is “quenching”?

a process by which electronically excited molecules or atoms, such as singlet molecular oxygen, are inactivated

talk about vitamin A deficiency

deficiency is inadequate intake occurring frequently in children in developing countries

symptoms include: dry, scaly skin, night blindness, bitot’s spots, xerophthalmia, keratinization

describe toxicity of vitamin A

• hypervitaminosis A: can cause liver damage, hemorrhage, teratogenic affects, or death

  • teratogen: molecules that cause birth defects

• beta-carotene causes hypercarotenemia but does not damage the liver. it may cause carotenoderma (orange discoloration of the skin)

what are the two kinds of vitamin D?

ergocalciferol: Vitamin D2

cholecalciferol: vitamin D3

vitamin D is naturally present in very few foods. Describe its presence in the skin, liver, and kidneys:

in the skin: in sunlight, 7-dehydrocholesterol is converted to vitamin D3

in the liver: vitamin D2 and D3 are hydoxylated to 25-hydroxyvitamin D3

in the kidneys: 25-hydroxyvitamin D3 is further hydroxylated to 1,25-dihydroxyvitamin D3 (also called calcitriol) this is the active hormonal form of vitamin D

what are the main functions of vitamin D?

• regulates gene expression

• calcitriol binds to vitamin D receptors (VDR) in the nucleus, and the vitamin D-receptor complex regulates gene expression of the target tissue

• vitamin D is also known for maintaining calcium homeostasis and bone remodeling

within the function of Vitamin D, calcitriol binds to vitamin D receptor in the nucleus, and the vitamin D-receptor complex regulates gene expression of the target tissue…what are the target tissues?

• small intestine: enhances calcium absorption

• kidney: promotes calcium reabsorption

• bone: enhances calcium release (osteoclast activity) from the bone

  • all to enhance blood calcium levels

talk about vitamin D deficiency

• can cause rickets (children) and osteomalacia (adults)

• rickets: bowed legs, short stature and broken bones due to failure of calcium metabolism and bone mineralization

• Osteomalacia: normally does not induce bone deformity but reduces bone mineral density which increases risk of fractures

name the multiple forms vitamin E exists as:

a- (alpha), b- (beta), y- (gamma), and (delta)-tocopherol.

structurally, what does vitamin E consist of?

aromatic rings and a hydrocarbon side chain

what are the best food sources for tocopherols and tocotrienols?

tocopherols: rich in leafy vegetables, veggie oils, seed oils

tocotrienols: barley, rice brans, palm oil

what is the difference between tocopherols and tocotrienols?

both are members of the vitamin E family but their structure is different.

tocopherols: saturated tail

tocotrienols: unsaturated tail with 3 double bonds

*tocopherols are more abundant in nature

what are the main functions of vitamin E?

1. vitamin E is an antioxidant

2. vitamin E is imbedded into cell membrane, scavenges free radicals, and prevents lipid peroxidation

what is lipid peroxidation?

the process of oxidative degradation of lipids by free radicals and reactive oxygen species (ROS)

discuss vitamin K and vitamin K2

vitamin K = phytomenadione = phylloquinone

• present in green leafy veggies

• absorbed in the small intestine

vitamin K2 = menaquinone

• produced by gut microbiome (provides ½ of a person’s needs) and some from animal products

• absorbed by passive diffusion from the ileum and colon

what are the functions of vitamin K?

vitamin K supports blood clotting

• some clotting factors must be carboxylated to be active

• Vitamin K supports carboxylation of these clotting factors 

• Cascade actions of vitamin K dependent-clotting factors eventually activates fibrinogen to fibrin

vitamin K is used for carboxylation reaction in bones

what is fibrin?

it is the insoluble fibrous protein that holds blood clots together

discuss vitamin K deficiency

vitamin K is well-absorbed and deficiency in adults is rare

infants: up to 6mo may be at risk for deficiency

newborns have sterile digestive tracks and are typically given a vitamin K shot at birth to support blood clotting

human milk contains a low concentration of vitamin k compared to cow’s milk

symptoms of deficiency include:

• bleeding

• bruising

list the 4 main minerals

1. calcium

2. iron

3. iodine

4. selenium

what are minerals? and what is the difference between major and trace minerals?

• Inorganic micronutrients

• Major mineral:

  • Mineral present in the human body in quantities greater than 5g

    • E.g. calcium, phosphate, potassium, sulfure, sodium, chloride, magnesium

• Trace mineral: 

  • Mineral present in the human body in quantities smaller than 5g

    • Eg. iron, manganese, copper, iodine

give a general breakdown of calcium

• Exists as positively charged ion (Ca2+) in solution

• The most abundant mineral in the body

• Food sources:diary products, dark green vegetables

list the three main functions of calcium

1. calcium supports bone formation

2. calcium regulates calcium-dependent protein

3. calcium acts as a second messenger

break it down: how does calcium support bone formation?

• 99% of the calcium in the body is stored in bones and teeth

• Low concentration of serum calcium stimulates parathyroid hormone (PTH) release, which activates calcitriol (the active form of vitamin D)

  • Calcitriol increases osteoclast activity (bone), calcium reabsorption (kidneys), and absorption (intestine)

• Composition of bone:

  • 20-40% organic matrix

  • 50-70% minerals!

  • 5-10% water

  • <3% lipids

how does calcium regulate calcium-dependent protein?

• Many proteins or enzymes have calcium binding sites

• Calcium binding regulates activity of the target proteins or enzymes

• Ex: calmodulin-Ubiquitour cytosolic protein that activates cellular kinases, and regulatory proteins

how does calcium act as a second messenger?

• Calcium is an intracellular signaling molecule that amplifies intracellular cell signaling cascade

• Ex: ligand-receptor binding opens IP3-gated calcium channel, and releases intracellular calcium

  • Calcium stimulates muscle contraction and neurotransmission

discuss calcium deficiency

Calcium deficiency contributes to muscle spasms, poor mineralization of bones and osteoporosis

• In children, rickets and impaired growth often happens with deficiency

what is iron? and discuss the two main forms of dietary iron

Iron is a trace element present in the body in ferric (Fe3+) and ferrous (Fe2+) forms

Dietary iron has two main forms:

• Heme iron:

  • Iron attached to heme

  • From animal foods

• Non-heme iron

  • From both plants and animal sources

discuss the difference between heme and non-heme iron absorption

• Heme iron

  • Absorbed intact by a heme carrier protein (hcp1)

  • Heme iron is more easily absorbed than non-heme iron

• Non-heme iron

  • Ferric ion (Fe3+) is reduced to ferrous ion (Fe2+) and Fe2 is absorbed by divalent cation transporter DMT1

• Sugars, acids, vitamin C, and meat increase iron absorption

• Polyphenols, oxalic acid, phytic acid, and divalent cations decrease iron absorption

list the three players in iron transport and storage

1. transferrin

   1. major plasma protein involved in the transport of iron

   2. a type of glycoprotein with 2 iron-binding sites

2. transferrin receptor

   1. high affinity receptor of transferrin

   2. involved in cellular uptake of iron from the circulation

3. ferritin

   1. iron storage protein

   2. serves as an iron reservoir in liver, spleen, and skeletal muscle

   3. ferritin can sequester or release iron, depending on the body’s needs

what is the main function of iron-heme protein?

iron is a major component of heme protein

what are the two types of iron-heme proteins?

1. hemoglobin

   1. quaternary protein with 4 subunits that carries oxygen in circulation

2. myoglobin

   1. oxygen binding protein in muscle tissue

where are heme proteins found?

in the electron transport chain

• cytochrome

• complex IV

which antioxidant enzymes have heme?

peroxidase

catalase

talk about iron deficiency AND toxicity

DEFICIENCY:

• The most common nutrient deficiency in the world!

• Iron-deficiency anemia: characterized by small, pale RBCs containing inadequate hemoglobin and a decreased number of RBCs

TOXICITY

• Iron-toxicity is also very common

• Hemochromatosis: 

  • excess iron is stored in the liver, heart, and pancreas

  • Excess iron stored in organs poisons them and leads to life-threatening conditions such as cancer, heart arrhythmias, and cirrhosis

what is the predominant form of iodine found in nature?

anion iodide (I-)

what are the main food sources of iodine?

seafood including fish and seaweed

table salt is iodized to ensure adequate intake (in US)

what is the main function of iodine in the body?

Iodine is required for the synthesis of thyroid hormones:

• Thyroxine (T4)

• Triiodothyronine (T3)

what do thyroid hormones do?

regulate glucose homeostasis

heart rate

blood pressure

body temperature

growth and development

talk about iodine deficiency

• Thyroid hormone release as related to iodide deficiency

  • This stimulates various thyroid functions like hyperplasia

what is goiter?

an enlarged thyroid gland

name the multiple forms selenium exists as

selenide (Se2-)

selenite (SeO3,2-)

selenate (SeO4,2-)

selenium

what are the food sources for selenium?

present in both plant and animal products

selenium content in soil influences the selenium levels in food

what re the main functions of selenium?

selenium acts as a cofactor for enzyme

• Glutathione peroxidase 

  • An antioxidant enzyme that converts hydroperoxide to water using glutathione

• Thioredoxin reductase

  • An enzyme that regenerates thioredoxin, a critical player in antioxidant defense

discuss the two main types of deficiency for selenium

DEFICIENCY

• Keshan disease

  • Cardiomyopathy

• Kashin-beck’s disease

  • Osteroarthropathy