Nplex Biochem Nutritional

NPLEX - Nutritional Biochemistry Water Soluble Vitamins - rarely accumulate to toxic concentrations because they are readily eliminated through the urine - storage is difficult, so they must be taken in through the diet quite regularly - includes all the B vitamins and Vitamin C Vitamin Deficiency Active Form Absorption B1 (Thiamin) - results in Beriberi - thiamine TPP is hydrolyzed to - the symptoms of which may include pyrophosphate thiamine in the GI tract weight loss, emotional disturbances, (TPP) - it can then be absorbed impaired sensory perception - aka. Thiamine in the jejunum or ileum (Wernicke's encephalopathy), diphosphate weakness and pain in the limbs, and periods of irregular heartbeat. Swelling of bodily tissues (edema) is common - diet of polished white rice which is thiamine deficient

Sources - milk - wheat germ - whole grain cereals - seeds - nuts - yeast - legumes - chicken - fish & pork

Biochemical Functions

- FMN & FAD serve as prosthetic groups attached to oxidoreductase enzymes (aka flavoproteins) - Eg. Succinate dehydrognease of the Krebs cycle & ETC - xanthine oxidase for the production of uric acid - fatty acyl-CoA dehydrogenase in FA oxidation - synthesis of the active form of folate -enzymes in choline catabolism & glutathione reductase - the thiol group of CoA and ACP acts as a carrier of acyl groups

B2 (Riboflavin)

- results in pallor, angular stomatitis, cheilosis, - oral-buccal cavity lesions - erythematous, greasy rash in patches - “shark skin” appearance

FMN & FAD

- dietary FMN and FAD are hydrolyzed to riboflavin in the GI tract so it can be absorbed in the duodenum and jejunum

-milk & milk products - eggs - green vegetables - organ meats - legumes - wheat germ

B5 (Pantothenic Acid)

- unlikely

- Coenzyme A - ACP

- CoA is hydrolyzed to panthetheine, then pantethenic acid in the gut, then absorbed in the jejunum

-virtually everywhere - meats - egg yolk - vegetables - whole grains - legumes - mushrooms - royal jelly - liver - mackerel, salmon - bananas - vegetables - eggs, chicken - wheat germ, yeast - legumes

B6 (Pyridoxine – doxal, doxamine)

- neuropathies - anemia - hyperhomocysteinemia - many other diseases/sx: PMS, fibrocystic breasts, etc.

- pyridoxal phosphate (PLP)

- PLP is dephosphorylated in the gut to enhance absorption in the small intestine - B6 aids in the absorption of magnesium

Vitamin

Deficiency

Active Form

Absorption

Sources

- TPP is needed as a co-enzyme in rxns that involve the transfer of an activated aldehyde unit, as in oxidative decarbosylation of alpha-keto acids or transketolase rxns - role in energy transformtation - synthesis of pentoses and NADPH (in pentose phosphate pathway) - membrane/nerve conduction

- The attachment of CoA activates the compound for the production of energy, protein acetylation, or FA synthesis - PLP is a coenzyme of several enzymes involved in amino acid decarboxylation rxns (eg. Tryptophan  serotonin or glutamic acid  gamma-aminobutyric acid [GABA]) - and transaminase rxns in amino acid metabolism Biochemical Functions

B12 (Cobalamins)

- megaloblastic anemia - macrocytic anemia - hyperhomocysteinemia - also, neurological diseases - including dementia

methylcobalamin - deoxyadenosylcobalmin

- absorption of food-bound B12 (which is by far the m/c form) requires intrinsic factor In the terminal ileum - IF is released from gastric parietal cells - free B12 is absorbed w/out intrinsic factor but is very scarce in diet (but common in supplements)

- liver - kidney - eggs - cheese - fish - milk

- deoxyadenosylcobalmin is a coenzyme for the conversion of methylmalonyl-CoA to succinyl Co-A in gluconeogenesis. - Methylcobalamine is a coenzyme in the conversions of homocysteine to methionine and methyltetrahydrofolate to tetrahydrofolate (THF) - this helps maintain stores of methionine & create tetrahydrofolate needed in nucleotide & nucleic acid synthesis

- large portion is met by synthesis in the normal flora of the gut - liver - soybeans - egg yolks - legumes - tomato - yeast - liver - alfalfa - green vegetables - lima beans - yeast

- functions as a coenzyme for carboxylase enzymes like pyruvate carboxylase in gluconeogenesis and acetyl-CoA carboxylase in FA synthesis

- colourful fruits & veggies – asparagus, papaya, citrus, broccoli, bell peppers, kale, cantaloupe, strawberries, rosehips, cranberries, cabbage, spinach

- ascorbic acid serves as donor of reducing equivalents in hydroxylation rxns to keep metal cofactors in the reduced state - Ascorbic acid also helps to regenerate vitamin E and acts as an anti-oxidant

Biotin

- no disease associated with deficiency - seborrheic dermatitis has been proposed

Carboxybiotin

- biotin is proteolytically cleaved from its carrier protein for absorption in the jejunum - inhibited by avidin – found in raw egg whites

Folic Acid

- megaloblastic & macrocytic anemia - neural tube defects (maternal deficiency) - hyperhomocystenemia

-tetrahydrofolate (THF)

- The polyglutamate forms of folate need to be hydrolyzed by conjugases into monoglutamate forms that can be absorbed in the jejunum - conjugase inhibitors are in foods like cabbage, lentils, legumes & oranges

Vitamin C

- scurvy

- Ascorbic acid

- occurs in the ileum via sodium-dependent active transporter

(Ascorbic Acid)

- vit C enhances absorption of iron through chelation

FAT SOLUBLE VITAMINS - require fat for absorption in the gut - can be stored in adipose tissue, because it is fat soluble

- THF serves as a cofactor by acting as a carrier of activated one-carbon units: methyl-THF, methylene-THF, and formyl-THF - THF is needed in amino acid metabolism of serine, glycine, methionine, & histidine. - It also plays an important role in the synthesis of purines & pyrimidines

Rxns that it participates in: - converision of praline  hydroxyproline and lysine  hydroxylysine in collagen synthesis - conversion of lysine  carnitine - cholesterol  α-hydroxycholesterol for bile acid synthesis, tyrosine synthesis & catabolism & conversion of dopamine  norepinephrine

- can lead to toxicity if they are taken in excess Vitamin Deficiency Vit A - high levels are teratogenic & promote osteoporosis (Retinol, Retinoic Acid) - low levels night blindness & xerophthalmia

Vit D Ergocalciferol [D2], Cholecalciferol [D3]

Vit E

- rickets in children - osteomalacia in adults - strong risk factor for many forms of cancer - excess levels can promote systemic calcification & hypertension

1,25-dihydroxycholecalciferol (1,25-OH2) D3)

* RDA has been increased, and it is believed that far more ppl are deficient than previously thought - esp. in low-sun climates - neurologic disease - cancer, atherosclerosis - xs levels may  hypertension

D-alpha Tocopherols & tocotrienols

- hemorrhage & osteoporosis - may be a risk factor for cancer

- Hydroquinone

Menaquinone [K2]

General / Deficiency

Sources - liver - dairy - tuna, sardines - dark green & yellow veggies - Beta-carotene from fruits and veggies is converted to 2 molecules of retinol

Biochemical Functions - retinol & retinoic acid act like steroid hormones to aid in the differentiation & growth of epithelial cells - retinoic acid also participates in glycoprotein synthesis, which is important in cell signalling. - retinol is needed in reproductive processes & anti-body synthesis - retinal is incorporated into the visual pigment rhodopsin for vision

- most requirements are met by synthesis of D3 from 7dehydrocholesterol in sun-exposed skin

- calcitrol works in conjunction with parathyroid hormone to maintain adequate calcium levels in the blood by increasing the absorption of Ca2+ in the intestines  stimulating Ca2+ release from bone  stimulating Ca2+ reabsorption in the kidneys

Food sources: - liver, beef, veal - eggs, fortified dairy - fish oils

Phylloquinone [K1],

Mineral

Absorption - retinol is found as esters bound to protein - hydrolysis occurs to remove the protein, and esterase converts retinyl esters to reinol that can be absorbed into micelles for absorption in the duodenum and jejunum. Retinol is reesterfied for transport in chylomicrons - vit D is absorbed in the jejunum or ileum in the presence of fat and bile salts

- aka. Calcitriol

Tocopherols

Vit K

Active Form - retinol - retinal - retinoic acid

Enzymes

- absorption requires the presence of fat & bile acids in the jejunum for incorporation into chylomicrons - vit K absorption requires the presence of fat and bile acids for absorption in the distal ileum & colon

MACROMINERALS Absorption / Distribution

- vegetable oils - seed oils - leafy green veggies

- Vit E is one of the most important antioxidants against peroxidation of polyunsaturated FA in cellular membranes

K1: plant sourcesleafy green veggies, legumes, & soybean oil

- vit K is required for the synthesis of blood clotting factors II, VII, IX & X.

K2: greatest concentration provided by the bacteria of the colon

- it is a cofactor for the gammacarboxylation rxns of glutamic acid residues in proteins to better bind Ca2+ (eg. In the kidney to prevent kidney stone formation) - Vit K is a cofactor in the synthesis of 2 bone proteins (osteocalcins) important in the bone matrix

Sources

Biochemical Functions

Calcium

Phosphorus

Potassium (K) (also an electrolyte)

Sodium (Na)

Bone and tooth formation Blood clotting (fibrin) Muscle and Nerve action Metabolic reactions Absorption of B12 Decrease hypertension Decrease colon cancer risk Rickets – bone Tetany – blood Osteoprosis Hypercalcuria energy metabolism regulation of enzyme activity component of phospholipids acid/base balance hormonal controls  vit D and PTH Weakness, loss of appetite, fatigue and pain - major intracellular cation

-99% is stored in bones - most abundant cation in the body

ATPase Involved in glycogen breakdown

- long use of ant-acids binds P and blocks absorption

Ratio of Na/K+ critical for nomal cell function Inside cell Na/K+ = 1/10 Outside cell Na/K+ = 28/1

Prolonged V & D, diuretic drugs severe malnutrition Muscle weakness Bloating Cardiac arrest Weakness of resp mm: breathing problems - major extracellular fluid cation

Mineral

General metabolism Body has reserves Kidney can reabsorb it Protein and DNA synth. Muscle relaxant Vit D metabolism 60% in bones Low intake Increased excretion V & D, surgical trauma Increase Ca intake Excess alcohol excretion Muscle weakness tetany like state with tremors to convulsive seizure

General / Deficiency

- major function is in the mineralization of both cortical (compact) bone and trabecular (spongy) bone

High protein foods Milk, meat, fish, eggs Cereal grains Legumes, nuts Too much in softdrinks

- helps Ca2+ in mineralization of bone - important constituent of DNA, RNA, cell membranes & the high-energy bonds of ATP - enzyme regulation via phosphorylation or dephosphorylation - intracellular buffer (acid-base) - oxygen delivery

Unprocessed foods: Fruits, veggies and fresh meat Bananas, Spinach

Insulin release Blood pressure/H20 balance Synthesis of glycogen, protein and energy Vital for heart muscle

- non-osseus Ca2+ essential in: • Contraction of skeletal, smooth and cardiac muscle • Membrane permeability • Nerve signals • Blood coagulation • Enzyme regulation

*water in cooking can leach out K+

Weakness Headache Muscle cramps shock

Magnesium (Mg)

- 2nd most abundant mineral - 90% in bones as hydroxyapatiteCalcium phosphate

Milk products, Egg yolks Grains, legumes, nuts Swiss chard, beet greens, spinach, rhubarb Fiber may bind it Oxalates & phytates have less available Broccoli, mustard & turnip Dolomite(may contain lead)

Binds to enolase or ATP and puts it in correct shape so it can function properly

Enzymes

Major electrolyte – helps maintain normal fluid and electrolyte balance between intra and extracellular compartments

Animal origin Milk, meat, eggs NaCl Carrots, beef, leafy greens

Body H20 balance Muscle contraction Nerve impulses Glucose absorption

- 55% of Mg is found in bone, - 27% in muscle & rest in extracellular tissues

Nuts, legumes Unrefined grains Green veggies Chlorophyll Milk, cheese, meat Seafood Hard water

- cofactor for many enzymatic rxns involving ATP: protein and FA synthesis, cAMP formation, RNA & DNA synthesis, activation rxns of B1  TPP & vitamin B6  PLP & muscle contraction

Sources

Biochemical Functions

MICROMINERALS Absorption / Distribution

Iron (Fe) Tiredness, headache, depression, irritability Pallor, dyspnea, palpiations, reduced capacity for work or prolonged exercise, behavior and intellectual impairment, reduced resistant to infection and impaired temp regulation

- Fe-containing enzymes, transferrin in blood - ferritin in liver, spleen or bone marrow

- found as constituent in Hb, myoglobin Toxicty Hemosiderosis – excess storage of iron in liver as hemosiderin  can be lethal

Meat, fish, poultry Broccoli, Cabbage, Orange, Tomatoes Legumes (Cheese, Eggs, Milk are less bioavailable)

Bone marrow becomes hyperplastic Synthesis of carnitine, purines, and collagen

Damage to liver and pancreas  leads to metabolic problems

Selenium (Se)

Cells anti-oxidant protective system Arachadonic acid metabolism T4  T3 Keshan disease cardiomyopathy in kids and women when intake low Muscle pain, weakness Loss of pigmentation Decrease Se in plasma Decrease Glutathione peroxidase levels in RBC

Glutathione peroxidise

Food content reflected in soil content Organ meats>muscle meats>cereals>diary products Lost in milling and boiling

General metabolism Body has reserves Kidney can reabsorb it

General / Deficiency

Hb needs iron to bind O2 * Ferrous form when O2 bound - component of the enzyme glutathione peroxidise which helps destroy free radicals - provides protection against heavy metal toxicity through detox pathway (P450) * Note: Se levels inversely related to cancer mortality - involved in detox of certain carcinogens

- chromium is thought to be stored with iron in KI, LV, muscle, spleen, Heart, pancreas & bone

Low intake Increased excretion V & D, surgical trauma Increase Ca intake Excess alcohol excretion Muscle weakness tetany like state with tremors to convulsive seizure Muscle weakness tetany like state with tremors to convulsive seizure

Mineral Fluorine, &

- found in high amounts in KI, HT, LV, pancrease and Muscle

Type I iodothronine 5-deiodinase (T4 T3)

Chromium (Cr)

Manganese (Mn)

- O2 Transport on Hb - Storage of O2 on muscle myoglobin - Cofactor in ETC to make ATP - Activation of O2 in WBCs to kill bacteria - B-caroteneVitamin A - Detoxification - Neurotransmitter synthesis

Binds to enolase or ATP and puts it in correct shape so it can function properly

60% in bones

Nuts, legumes Unrefined grains Green veggies Chlorophyll Milk, cheese, meat Seafood Hard water

Enzymes

Absorption / Distribution

Sources

- distributed in hard calcified tissues

- Chromium combines with nicotinic acid and amino acids to form glucose tolerance factor (GTF) - GTF aids in the formation of disulfide bridges between insulin & its receptor  improves the effectiveness of insulin & enhances glucose uptake Protein and DNA synth. Muscle relaxant Vit D metabolism

Biochemical Functions - promotes mineral precipitation to form

Fluoride (F) Copper (Cu)

Rare – babies on parenteral nutrition and then cow’s milk Iron & Vit C inhibit absorption

* see biochemical functions for coenzyme actions

Psychomotor retardation Pallor, anemia, osteoporosis Menke’s Kinky hair syndrome  defective Cu absorption and transport Slow growth, seizures, brain degeneration, hypothermia, stubby white hair

Cause:

Excess alcohol Malabsorption syndromes Surgery, burns KI disease Acrodermatitiis enterpathica Sx:

Impaired growth, development, sexual maturity and functioning of immune system Loss of hair and taste Poor wound healing

apatite in a protein matrix

- found in either the cuprous (+1) or cupric (+2) forms in muscle, bone, liver, kidney, or brain tissue

- copper is an important co-enzyme for several oxidases like cytochrome aa3 in the ETC - enzymes in estrogen degradation - cytosolic SOD for the defense against free radicals

Wilson’s disease  inability to excrete Cu in bile Anemia and liver damage Penicillamine chelation

Cofactor in >70 enzymes

Zinc (Zn)

like teeth and bones

Superoxide dismutase -Carbonic anhydrase -Alcohol dehydrogenase - Alkaline phosphatase -DNA polymerase -Glutamate dehydrogenase

Levels in brain, HT, LU and muscle are constant 95% in muscle and bones

Synthesis of collagen Synthesis of noradrenaline Synthesis of melanin Iron transport mechanism Stinulates Hb synthesis

Oysters Meat, poulty, eggs, dairy Grain products > fruits and veggies Lost in milling Fibrous unleavened bread is a problem

See page 159 for discussion of Other Non-Vitamin Anti-Oxidants

- Taste perception - Night vision - Normal growth – works in conjunction with vitamin A - Reacts with insulin - Binds to hormones - Immune system - collagen synthesis - needed to mobilize iron in the liver