Nutrition 3 Lecture 4 PDF

NUTRITION III Nikita Sahadeo, Ph.D. Biochemistry Unit Department Of Preclinical Sciences Faculty of Medical Sciences University of the West Indies January 2024 ABSORPTION OF FAT-SOLUBLE VITAMINS The body absorbs fat-soluble vitamins into newly forming micelles in the small intestine After absorption...

NUTRITION III Nikita Sahadeo, Ph.D. Biochemistry Unit Department Of Preclinical Sciences Faculty of Medical Sciences University of the West Indies January 2024 ABSORPTION OF FAT-SOLUBLE VITAMINS The body absorbs fat-soluble vitamins into newly forming micelles in the small intestine After absorption into enterocytes, fat-soluble vitamins become packaged into chylomicrons, which then get secreted into the lymphatic system before entering the bloodstream Chylomicrons are metabolized by lipoprotein lipase, which causes the release of fat-soluble vitamins into tissues for use and storage Because they are stored in tissue, the fat-soluble vitamins are retained by the body for a longer time than the water-soluble vitamins VITAMIN A Also known as retinol Retinol used to synthesize retinal OTHER FUNCTIONS OF VITAMIN A Plays an integral role in the differentiation and proliferation of epithelial cells in the eyes, salivary glands, and genitourinary tract. A precursor to the nuclear hormone all-trans retinoic acid, which heterodimerizes with retinoic acid receptors (RAR) in the nucleus. RAR-retinoid X receptor heterodimers serve as transcription factors that bind certain elements in promoters of genes which encode important structural proteins, extracellular matrix proteins, and enzymes throughout the body. Stimulates T-lymphocyte differentiation and B-lymphocyte activation in response to immune stimuli. VITAMIN A DEFICIENCY Defined clinically or sub-clinically Xerophthalmia is the clinical spectrum of ocular manifestations of vitamin A deficiency; these range from the milder stages of night blindness and Bitot spots to the potentially blinding stages of corneal xerosis, ulceration and necrosis (keratomalacia). The various stages of xerophthalmia are regarded both as disorders and clinical indicators of vitamin A deficiency. Retinol is the main circulating form of vitamin A in blood and plasma. Serum retinol levels reflect liver vitamin A stores when they are severely depleted or extremely high; however, between these extremes, plasma or serum retinol is homeostatically controlled and hence may not correlate well with vitamin A intake. VITAMIN A DEFICIENCY Keratomalacia Follicular hyperkeratosis: keratin deposits form around hair follicles; causes rough texture to the skin resembling 'goose flesh;' facial skin scaly, off-colour, cracked, or dry to the point of flaking. VITAMIN D Vitamin D is a collective term used to refer to any one of 4 similar substances, only one of which has biological activity: ergocalciferol (D2 from plants); cholecalciferol (D3 from animals); 25-hydroxyvitamin D (circulating form); 1,25-dihydroxyvitamin D (calcitriol, active form). VITAMIN D NEEDS VITAMIN D DEFICIENCY Required Dietary Allowance: children: 10 micrograms/day (400 IU); adults: 20 micrograms/day (800 IU); pregnancy and lactation: 25 micrograms/day (1000). In children causes rickets In adults causes osteomalacia VITAMIN E Potent antioxidant that prevents oxidation of fatty acids Protects lipids in membranes from oxidative damage: particularly phospholipids of mitochondria and endoplasmic reticulum, which are more unsaturated; cell membranes of lung, brain, and erythrocytes also susceptible. Protects erythrocytes from hemolysis by oxidising agents VITAMIN K THE VITAMIN K CYCLE FUNCTIONS OF VITAMIN K Cofactor for the enzyme, γ-glutamylcarboxylase, which catalyzes the carboxylation of the glutamic acid to γcarboxyglutamic acid Vitamin K-dependent γ-carboxylation that occurs only on specific glutamic acid residues in identified vitamin K-dependent proteins (VKDP) is critical for their ability to bind calcium The ability to bind Ca2+ is required for the activation of the several vitamin K-dependent clotting factors in the coagulation cascade VITAMIN K DEFICIENCY Risk factors: antibiotic use, nutritional deficiency, and high ingestion of vitamins A and E Newborns are at risk for deficiency due to immature gut flora, poor placental transfer, and low content in breast milk A common clinical syndrome that results from vitamin-K deficiency is a hemorrhagic disease of the newborn In adults, deficiency can cause easy bleeding and bruising VITAMIN C Exists in reduced [ascorbate] and oxidized forms as dehydroascorbic acid which are easily inter-convertible and biologically active thus it acts as important antioxidant. Easily oxidized acid and destroyed by oxygen, alkali and high temperature Most of the plant and animal species have the ability to synthesize vitamin C from glucose and galactose through uronic acid pathway but humans and other primates cannot do so because of deficiency of enzyme gulonolactone oxidase FUNCTIONS OF VITAMIN C Helps in the synthesis and metabolism of tyrosine, folic acid and tryptophan, hydroxylation of glycine, proline, lysine carnitine and catecholamine. Facilitates the conversion of cholesterol into bile acids and hence lowers blood cholesterol levels Increases the absorption of iron in the gut by reducing ferric to ferrous state. As an antioxidant, it protects the body from various deleterious effects of free radicals, pollutants and toxins. Biochemical functions are largely dependent on the oxido-reduction properties of l-AA which is a co-factor for hydroxylation and activity of mono-oxygenase enzymes in the synthesis of collagen, carnitine and neurotransmitters. Accelerates hydroxylation reactions by maintaining the active centre of metal ions in a reduced state for optimal activity of enzymes hydroxylase and oxygenase.Thus, it is crucial in the maintenance of collagen which represents about one-third of the total body protein. FUNCTIONS OF VITAMIN C A co-factor for the enzyme dopamine-β-hydroxylase, which catalyzes the conversion of neurotransmitter dopamine to norepinephrine and hence essential for the synthesis of catecholamines Catalyzes other enzymatic reactions involving amidation necessary for maximal activity of hormones oxytocin, vasopressin, cholecystokinin and alphamelanotropin Involved in the transformation of cholesterol to bile acids as it modulates the microsomal 7α-hydroxylation, the rate limiting reaction of cholesterol catabolism in liver VITAMIN C DEFICIENCY Required Dietary Allowance: adults: 60 mg/day; children: 40 mg/day. Severe vitamin C deficiency causes scurvy. Adults feel tired, weak, and irritable if their diet is low in vitamin C. They may lose weight and have vague muscle and joint aches. The symptoms of scurvy develop after a few months of deficiency. Bleeding may occur under the skin (particularly around hair follicles or as bruises), around the gums, and into the joints. The gums become swollen, purple, and spongy. The teeth eventually loosen. The hair becomes dry, brittle, and coiled (like a corkscrew), and the skin becomes dry, rough, and scaly. Fluid may accumulate in the legs. Anemia may develop. Infections may develop, and wounds do not heal. Infants may be irritable, have pain when they move, and lose their appetite. Infants do not gain weight as they normally do. In infants and children, bone growth is impaired, and bleeding and anemia may occur. TYPES OF MINERALS & THEIR FUNCTIONS There are hundreds of minerals – they are usually classified as either major or trace minerals. Although the amount you need differs between minerals, major (or macrominerals) are generally required in larger amounts. Some examples include calcium, phosphorus, potassium, sulphur, sodium, chloride, magnesium. Trace minerals (microminerals), although equally important to bodily functions are required in smaller amounts. Examples include iron, zinc, copper, manganese, and iodine selenium. Fulfil the following functions: co-factors of enzymes; electrolytes; structure of tissues such as: bones, teeth, nails, blood, nerves cells, and muscles. CALCIUM Most abundant mineral 99% of the body’s Ca exists in bones and teeth: provide structure and strength; serve as a reserve bank that can release Ca when blood level drops. bones are a bank from which Ca may be drawn or returned. In times of need: Ca absorption from the intestine is increased; loss from the kidneys is reduced. 1% of Ca in fluids that bathe and fill cells FUNCTIONS OF CALCIUM Regulation of ion transport Maintenance of blood pressure Blood clotting Muscle contraction Secretion of hormones, digestive enzymes, and neurotransmitters Activation of cellular enzymes. HYPOCALCEMIA Low blood Ca causes tetany, characterised by: paresthesias (tingling, burning, pricking, or numbness) of the lips, tongue, fingers and feet; carpopedal spasm, which may be prolonged and painful; generalised muscle aching; spasms of facial musculature. Although Ca is typically measured in labs from blood plasma, tetany is caused by low ionic Ca in extracellular and intracellular fluid. CALCIUM LOSS WITH AGE Bone loss is an inevitable consequence of ageing. It can be reduced by a good diet and exercise. Obtaining enough Ca in childhood helps ensures the skeleton starts adulthood with a high bone density. Osteoporosis, or adult bone loss, occurs if a person’s Ca bank is not sufficient. A diet low in Ca during the growing years may prevent the achievement of peak bone mass. PHOSPHOROUS 85% of body’s phosphorus found combined with Ca in bones and teeth Phosphorus also: helps maintain acid-base balance; is part of nucleic acids (DNA, RNA); involved in energy metabolism (ATP, GTP); is part of cell membranes (phospholipids). SOURCES OF PHOSPHOROUS PHOSPHOROUS DEFICIENCY A phosphorus deficiency is called hypophosphatemia, defined by blood levels that fall below the normal range. The most common causes of deficiency are kidney problems or a condition called hyperparathyroidism, in which too much parathyroid hormone is released that causes phosphorus to exit the body through urine. Also, the overuse of aluminum-containing antacids can bind to phosphorus and increase the risk of a deficiency. A notable but less common occurrence of hypophosphatemia occurs with refeeding syndrome, seen in people with severe malnutrition. Symptoms appearing with a phosphorus deficiency: Poor appetite Anemia Muscle weakness Bone pain Bone disease (osteomalacia, rickets) Confusion Increased susceptibility to infections MAGNESIUM Naturally present in a variety of foods, available as a supplement, and an ingredient in antacids and laxatives. Plays an important role in assisting more than 300 enzymes to carry out various chemical reactions in the body such as building proteins and strong bones, and regulating blood sugar, blood pressure, and muscle and nerve functions. Acts an electrical conductor that contracts muscles and makes the heart beat steadily. More than half of the magnesium in our body is stored in bones, and the remaining in various tissues throughout the body. MAGNESIUM Acts as an activator of many enzymes especially those involving transfer of phosphate groups from ATP such as: hexokinase; phosphofructokinase. Mg also activates a number of enzymes such as: enolase; glucose-6-P dehydrogenase; pyruvate carboxylase; thiokinase; glucose 6 phosphogluconate dehydrogenase SOURCES OF M AG N E S I U M MAGNESIUM DEFICIENCY Although magnesium is naturally found in a variety of foods and some fortified foods, many people eat less than recommended amounts. However, these deficiency levels are marginal and not likely to produce symptoms. The body also helps to preserve magnesium levels when stores are low by limiting the amount excreted in urine and absorbing more magnesium in the gut. A true deficiency occurs with a long-term low magnesium diet, malabsorption, and large losses from alcohol abuse or use of medications that deplete magnesium (some diuretics, proton pump inhibitors, and antibiotics). Signs of deficiency include: Fatigue, weakness Poor appetite Nausea, vomiting Numbness or tingling in skin Muscle cramps Seizures Abnormal heart rate SODIUM The major cation of the extracellular fluid Roles: maintenance of electrolyte balance of body fluid; essential for nerve transmission; involved in active transport of glucose, galactose, and amino acids across intestinal mucosa. 30 to 40 % of body’s Na on surface of bone crystals where it is easily drawn upon to replenish blood concentrations CHLORIDE Helps to regulate the amount of fluid and types of nutrients going in and out of the cells. Absorbed in the small intestine and remains in the body’s fluids and blood. Any excess amount is excreted in urine. Chloride is usually bound to sodium, and therefore the amount in blood tends to coincide with sodium levels. Deficiency A loss of chloride in the body usually accompanies conditions that cause sodium losses. These include conditions that remove too much fluid from the body, such as prolonged diarrhea, vomiting, or excessive sweating. Diuretic medications that remove fluid through the kidneys can also cause decreased chloride levels. In cases of sudden, very high levels of blood glucose such as seen in people with diabetes, the kidneys will flush more sodium and water out of the body, leading to lower chloride levels. Toxicity Toxicity from the diet is rare in healthy people. Excess chloride levels in the blood, called hyperchloremia, can be caused by severe dehydration, diarrhea, or metabolic problems in which the blood becomes too acidic, such as with kidney disease. A high salt diet can lead to an excessive intake of sodium chloride, which is associated with elevated blood pressure. Symptoms of toxicity: Muscle weakness High blood pressure Fatigue POTASSIUM Sometimes referred to as an electrolyte because it carries a small electrical charge that activates various cell and nerve functions. Potassium is found naturally in many foods and as a supplement. Its main role in the body is to help maintain normal levels of fluid inside our cells. Sodium, its counterpart, maintains normal fluid levels outside of cells. Potassium also helps muscles to contract and supports normal blood pressure. SOURCES OF POTASSIUM POTASSIUM DEFICIENCY & TOXICITY Deficiency The kidneys work to maintain normal blood levels of potassium by flushing out excess amounts through urine. Hypokalemia is most common in hospitalized patients who are taking medications that cause the body to excrete too much potassium. It is also seen in people with inflammatory bowel diseases (Crohn’s disease, ulcerative colitis) that may cause diarrhea and malabsorption of nutrients. It is rare for a potassium deficiency to be caused by too low a food intake alone because it is found in so many foods; however an inadequate intake combined with heavy sweating, diuretic use, laxative abuse, or severe nausea and vomiting can quickly lead to hypokalemia. Another reason is a deficiency of magnesium, as the kidneys need magnesium to help reabsorb potassium and maintain normal levels in cells. Fatigue Muscle cramps or weakness Constipation Muscle paralysis and irregular heart rate (with severe hypokalemia) Toxicity Certain situations can lead to hyperkalemia: advanced kidney disease, taking medications that hold onto potassium in the body (including NSAIDs), or people who have compromised kidneys who eat a high-potassium diet (more than 4,700 mg daily) or use potassium-based salt substitutes. Weakness, fatigue Nausea, vomiting Shortness of breath Chest pain Heart palpitations, irregular heart rate TRACE MINERALS Hard to determine precise roles in man as it is difficult to conduct experiments with diets lacking a single element Studies are generally done in laboratory animals that are fed controlled diets Only needed in small amounts. Include iron, manganese, copper, iodine, zinc, cobalt, fluoride and selenium IODINE An essential trace mineral not made by the body so must be obtained by food or supplements. Needed to make the thyroid hormones thyroxine and triiodothyronine, which assist with the creation of proteins and enzyme activity, as well as regulating normal metabolism. Without enough iodine, these thyroid hormones do not work properly and can lead to an under-active or overactive thyroid gland, causing the medical conditions of hypothyroidism and hyperthyroidism with various negative side effects in the body. SOURCES OF IODINE IODINE DEFICIENCY IRON Major component of haemoglobin and myoglobin Important for healthy brain development and growth in children, and for the normal production and function of various cells and hormones. Iron from food comes in two forms: heme and non-heme Heme is found only in animal flesh like meat, poultry, and seafood Non-heme iron is found in plant foods like whole grains, nuts, seeds, legumes, and leafy greens. Non-heme iron is also found in animal flesh (as animals consume plant foods with non-heme iron) and fortified foods. Iron is stored in the body as ferritin (in the liver, spleen, muscle tissue, and bone marrow) and is delivered throughout the body by transferrin (a protein in blood that binds to iron). SOURCES OF IRON IRON DEFICIENCY ANAEMIA Most commonly in children, women who are menstruating or pregnant, and those eating a diet lacking in iron. Iron deficiency occurs in stages. The mild form begins with a decrease in stored iron, usually either from a low-iron diet or from excessive bleeding. If this does not resolve, the next stage is a greater depletion of iron stores and a drop in red blood cells. Eventually this leads to iron-deficiency anaemia (IDA) where iron stores are used up and there is significant loss of total red blood cells. ZINC Necessary for almost 100 enzymes to carry out vital chemical reactions A major player in the creation of DNA, growth of cells, building proteins, healing damaged tissue, and supporting a healthy immune system Because it helps cells to grow and multiply, adequate zinc is required during times of rapid growth, such as childhood, adolescence, and pregnancy. Also involved with the senses of taste and smell. SOURCES OF ZINC ZINC DEFICIENCY Signs of deficiency include: Loss of taste or smell Poor appetite Depressed mood Decreased immunity Delayed wound healing Diarrhea Hair loss SELENIUM Found naturally in foods or as a supplement Essential component of various enzymes and proteins, called selenoproteins, that help to make DNA and protect against cell damage and infections. Selenoproteins are also involved in reproduction and the metabolism of thyroid hormones. Selenium in the body is stored in muscle tissue but the thyroid gland holds the highest concentration of selenium due to various selenoproteins that assist with thyroid function. SOURCES OF SELENIUM SELENIUM DEFICIENCY Two conditions are associated with severe selenium deficiency: 1) Keshan disease, a type of cardiomyopathy, or disease of heart muscle, and 2) Kashin-Beck disease, a form of osteoarthritis. Symptoms: Nausea, vomiting Headaches Altered mental state, confusion Lethargy Seizures Coma FLUORIDE Most recognized for its role in preventing and reversing dental caries and building strong teeth and bones. Most fluoride is absorbed in the gut and stored in bones and teeth. Unabsorbed fluoride is excreted in urine. Children absorb fluoride more efficiently than adults, as their teeth and bones are rapidly forming. Deficiency Fluoride is not considered an essential nutrient but plays an important role in dental and possibly bone health. A deficiency of fluoride can lead to dental caries and potentially bone problems. Infants and children who ingest more fluoride than needed can cause dental fluorosis. This condition only occurs as teeth are forming, producing permanent white spots or lines on teeth. In more severe cases, enamel may be lost and cause a brown staining of teeth A true fluoride toxicity is rare but may occur from excessive fluoride in water, whether occurring naturally or added, or accidental overconsumption of fluoride supplements. Symptoms include: Nausea, vomiting Abdominal pain Diarrhea Joint pain Skeletal fluorosis, or bone loss (from chronically excessive intakes) CHROMIUM Naturally present in a wide variety of foods, though only in small amounts, and is also available as a supplement. Chromium enhances the action of the hormone insulin. It is also involved in the breakdown and absorption of carbohydrate, proteins, and fats. Vitamin B3 and Vitamin C help to improve the absorption of chromium. Deficiency A chromium deficiency is rare, even though the mineral is poorly absorbed, with only about 5% or less absorbed in the gut. Diets high in refined sugars can cause more chromium to be excreted in the urine. Pregnancy and lactation, strenuous exercise, and physical stress from infections and trauma can also increase chromium losses. A risk of chromium deficiency increases with these scenarios if the diet is also low in chromium (most commonly seen with general malnutrition or acute illness that causes a deficiency of many nutrients). SOURCES OF CHROMIUM Chromium is found in small amounts in a range of foods. However, chromium content varies even among the same types of food, likely due to mineral variations in the soil in which it was grown. Chromium may also be inadvertently added into a food when it is processed with stainless steel equipment. Whole grains High-fiber bran cereals Certain vegetables: broccoli, green beans, potatoes Certain fruits: apples, bananas Beef Poultry, egg yolks Fish Coffee Brewer’s yeast Some brands of beer and red wine COPPER CONTAINING ENZYMES ceruloplasmin; cytochrome oxidase; dopamine oxidase; monoamine oxidase and diamine oxidase; cytoplasmic superoxide dismutase; lysyl oxidase (involved in the cross-linking process in the conversion of tropocollagen to collagen); tyrosinase of the melanin synthetic pathway. COPPER A naturally occurring metal found in soil, water, and rocks. Nutritionally, it is an essential trace mineral found in some foods and in supplements. It works to assist various enzymes that produce energy for the body, break down and absorb iron, and build red blood cells, collagen, connective tissue, and brain neurotransmitters. Also supports normal brain development and immune functions, and is a component of superoxide dismutase, an antioxidant enzyme that dismantles harmful oxygen “free radicals.” Copper is absorbed in the small intestine and found mainly in bones and muscle tissue. SOURCES OF COPPER COPPER DEFICIENCY A copper deficiency is rare in the U.S. among healthy people and occurs primarily in people with genetic disorders or malabsorption problems such as Crohn’s and celiac disease. A genetic condition called Menkes disease interferes with copper absorption, leading to severe deficiency that could become fatal without copper injections. Also, it is possible to create a copper deficiency by taking high doses of zinc supplements that can block the absorption of copper in the small intestine. Signs of deficiency include: Anaemia High cholesterol Osteoporosis, bone fractures Increased infections Loss of skin pigment MANGANESE A coenzyme that assists many enzymes involved in breaking down carbohydrates, proteins, and cholesterol Assists enzymes in building bones and keeping the immune and reproductive systems running smoothly. Works with Vitamin K to assist in wound healing by clotting the blood. Absorbed in the small intestine. Most of the mineral is stored in bone, with smaller amounts in the liver, brain, kidneys, and pancreas. Manganese levels are difficult to measure in the body as dietary intakes do not always correlate with blood levels. SOURCES OF MANGANESE