MMD Lecture 13 Nutrition Fall 2023.pptx

Nutrition Nutrition • Nutrition is the study of the substrate requirements of the organism. • Nutrition includes the chemistry of foods and the utilization of foods. • Nutritional concepts should be understood in biochemical terms. • Nutrition is an integral factor in the prevention and treatment...

Nutrition Nutrition • Nutrition is the study of the substrate requirements of the organism. • Nutrition includes the chemistry of foods and the utilization of foods. • Nutritional concepts should be understood in biochemical terms. • Nutrition is an integral factor in the prevention and treatment of disease. 2 Energy Content of Food • Energy content is calculated from the heat energy released upon total combustion of the food in a calorimeter. • In the body, a portion of the released energy is converted to ATP. • The major nutrients that provide energy in the diet are carbohydrates and lipids. To a lesser extent, proteins and alcohol provide energy. 3 Energy Requirements • The daily energy requirements take into account three energy-expending (energy-requiring) processes:  Resting metabolic rate  Thermic effect of food  Physical activity 4 5 Resting Metabolic Rate (RMR) • RMR represents the amount of energy needed to carry out normal body functions such as respiration, blood flow, maintaining neuromuscular integrity. • RMR is the metabolic rate measured at total rest, after not eating for 12 hours. • RMR is a function of size and shape, as well as age, sex, state of health. 6 Thermic Effect of Food • This is the increase in metabolic rate after eating. • The increase is small after a carbohydrate or lipid meal. The most marked effect is seen after protein ingestion, which could be as high as 30%. • Thermic effect of food represents the energy expended in the absorption of food. 7 Essential Nutrients Obtained From The Diet • Macronutrients – energy sources that include carbohydrates, lipids, and proteins • Essential fatty acids • Essential amino acids • Vitamins (micronutrients) • Minerals (micronutrients) 8 Recommended Dietary Allowances (RDA) • This is the daily amount required to maintain good health in a presently healthy person. • If RDA of carbohydrates is ~360g, lipids ~80g, and proteins ~56g. • What are the total kcal in the diet? • What percentage of total Calories comes • From carbohydrates? • From lipids? • From proteins? 9 10 Carbohydrates • The main metabolic role is energy production. • The major dietary carbohydrate is starch, a branched polymer of glucose. Depending on the diet, there is a variable amount of glycogen from muscle meat, and sucrose, glucose and fructose from plant material. • Glucose and fructose are rapidly absorbed. Plasma glucose level is the major stimulus for insulin secretion by the cells of the Islets of Langerhans. 13 Carbohydrates • Starch is digested mainly by pancreatic amylase. Final hydrolysis products are glucose, which is absorbed into mucosal cells and exits to the portal circulation. • When starch is eaten rather than monosaccharides (simple sugars), the eventual glucose is formed more slowly, and wide swings in plasma glucose are not seen. 14 Glycemic Index • Measures how fast and how much blood glucose rises after eating a food containing carbohydrates. 15 Carbohydrates • If dietary carbohydrate is too low, this will lead to ketosis and increase protein catabolism to support gluconeogenesis. • If dietary carbohydrate is in excess of energy needs, the glucose will be stored as triglycerides. 16 Lipids • Saturated fat- mainly from animal • raises total blood cholesterol levels and LDL • Trans fat-made during food processing through partial hydrogenation of unsaturated fats • Easier to cook with • Less likely to spoil • Cardiovascular risk: Increases LDL, lowers HDL Lipids • Monounsaturated fat- found in a variety of foods and oils • Improves blood cholesterol levels • May benefit insulin levels and insulin sensitivity • Polyunsaturated fat- mostly in plant-based foods • Improves blood cholesterol levels • Omega-3’s • Foods made up mostly of monounsaturated and polyunsaturated fats are liquid at room temperature, such as olive oil , safflower oil and corn oil Lipids • Essential fatty acids are linoleic acid and linolenic acid. • Linoleic acid is required for the synthesis of arachidonic acid, a precursor of eicosenoids (prostaglandins). Linoleic acid is found in safflower and corn oils. • Linolenic acid is found in canola and soybean oils. 19 20 Lipids • Dietary lipids are emulsified by bile salts and hydrolyzed by pancreatic lipases. • Main digestive products are fatty acids, monoacylglycerol, and cholesterol. • These are absorbed into mucosal cells, re-esterified to triglycerides and cholesterol esters, packaged into chylomicrons, and secreted into lymph. (Lacteals) • Short chain fatty acids are secreted into the capillaries, where they attach to albumin and are transported to the liver and the periphery. 21 Lipids • Dietary sources of cholesterol are egg yolks and organ meats. • Increased LDL is correlated with increased risk for coronary artery disease. • Increased HDL is correlated with decreased risk for coronary artery disease. • Serum cholesterol can be affected by dietary cholesterol intake, ratio of polyunsaturated fatty acids to saturated fatty acids, fiber content of the diet. 22 23 Proteins • Dietary proteins provide the building blocks, amino acids, necessary for renewal of body proteins. • Dietary proteins replace the N lost via turnover and also provide the essential amino acids. • Turnover of body protein is a feature of nitrogen balance. 24 Nitrogen Balance • A healthy adult is in nitrogen balance. If such a person increases the amount of protein in the diet, the excreted nitrogen will increase also to maintain balance. • If a healthy adult decreases the amount of protein in the diet, so long as essential amino acids are obtained, the amount of N excreted will fall to maintain balance. • If nitrogen intake exceeds nitrogen excretion, the body is said to be in positive nitrogen balance: the body is adding protein. • A growing child, pregnant woman, or one recovering from illness are in positive nitrogen balance – they are synthesizing protein. 25 N balance • If nitrogen excretion exceeds nitrogen intake, the body is in negative nitrogen balance. A person who has inadequate protein intake or is missing a single essential amino acid (starvation, dieting) will be in negative nitrogen balance – more protein will be degraded than synthesized. • In response to major trauma, injury, or illness, the body’s adaptive mechanisms cause an increase in catabolism of body proteins – a hypercatabolic response. 26 Proteins • Biologic value (BV) is a measure of the assortment of essential amino acids in a protein source that is incorporated in synthesizing tissue. • It is the quality of the protein, which is the measure of a protein to provide EAA required to maintain tissue. • The “ideal” protein is egg white, with biologic value of 100 percent. 27 Biologic Value And Protein digestibility-corrected amino acid score Accounts for both the amino acid composition of a food and the digestibility of the protein. It is a measure of the protein quality of a food. 28 The PDCAAS can be used to balance low protein quality foods with higher quality dietary proteins. Proteins • Amino acids, products of protein digestion, are absorbed from the small intestine by carrier-mediated active transport mechanisms. • Absorbed amino acids enter the portal circulation. Amino acids enter the cells of the body via active transport mechanisms. 31 Proteins • During fasting, the major source for the carbons appearing in glucose synthesized via gluconeogenesis are from amino acids transported from muscle to liver. • Muscle protein is degraded, and the amino acids are exported from the muscle. Most of the amino acids leaving the muscle are alanine and glutamine. • Use of amino acids for gluconeogenesis will be accompanied by increased output of urea. 32 Fiber • Fiber refers to material in the diet that are mostly carbohydrates but are not digestible by the enzymes of the GI tract. • Cellulose, found in cell walls of vegetables, is insoluble and fibrous. • Fiber can adsorb large molecules like bile salts and potentially carcinogenic material and cause their excretion in the feces. 33 34 Protein Energy Malnutrition • Protein Energy Malnutrition (PEM) is a deficiency syndrome caused by inadequate macronutrient and micronutrient intake. The causes include social, economic, biologic, and environmental factors. • Protein, energy and nutrient intake are all inadequate • Characteristics can range from kwashiorkor-like to marasmuslike. • Morbidity is due to fluid and electrolyte imbalances, opportunistic infections, decline in cardiovascular function, and anemia. 35 Protein Energy Malnutrition • PEM occurs in all parts of the world • Africa, south and central America, East and Southeast Asia, Middle east • In industrialized countries PEM occurs • Populations living in poverty • Older adults • Hospitalized patients with anorexia nervosa, AIDS, cancer • Two forms: Kwashiorkor and Marasmus Malnutrition • Kwashiorkor is a type of malnutrition seen in developing countries and is caused by a deficiency of protein in a diet that is adequate in calories. • Kwashiorkor results in lack of cellular development due to the failure to synthesize normal amounts of proteins. • There is hypoalbuminemia (reduced oncotic pressure) which leads to edema: there is also diarrhea, atrophy of the pancreas and intestinal mucosa. • Rarely observed in affluent countries 37 38 ascites in the abdomen Malnutrition • Marasmus is caused by a sever deficiency of both protein and total calories: chronic PEM. Protein, energy and nutrient intake are all inadequate. • This is generalized starvation, with symptoms including muscle wasting (emaciation), weakness, and anemia. • Seen in children 6 to 18 months who are fed diluted or poorly mixed formulas • Anorexia nervosa 40 Marasmus Obesity • Excess consumption + genetic component. • Adipocytes are larger (hypertrophy) and more numerous (hyperplasia) • Metabolic syndrome includes glucose intolerance, insulin resistance, hyperinsulinemia, elevated plasma triacylglycerol, hypertension, chronic inflammation. 42 Body Mass Index (BMI) • BMI is weight/height2 (kg/m2). • Normal BMI is 19-24.9. • Below 19 is underweight. • Above 25 is overweight. • Over 30 is obese. • Greater than 40 is morbidly obese. 46 he distribution of body fat is associated with health risk Waist/hip ratio >0.8 in women and >1.0 for men Upper body obesity Waist/hip ratio <0.8 in women and < 1.0 for men Lower body obesity xcess visceral and abdominal subq (in upper body) fat stores is observed with ease health issues associated with obesity. nce the pear shape has been shown to be protective, clinicians use the body shape hose who may be at higher risk for metabolic diseases Revisiting: Diabetes Twin Cycle Hypothesis • Research has demonstrated that fatty liver and insulin resistance are lead-up to the development of diabetes • Excess calories • Fatty liver leads to fatty pancreas • Dysfunction of both organs • Hepatic insulin resistance • Pancreatic-dysfunction Taylor R. Pathogenesis of Type 2 diabetes: Tracing the reverse route from cure to cause. Diabetologia 2008; 51: 1781–9. [ PubMed] Vitamins • Vitamins are micronutrients that we must obtain in the diet in small amounts. They are essential for normal growth and development. • Vitamins are organic molecules that are either watersoluble or fat-soluble. • Water-soluble vitamins – B complex and C. • Fat-soluble vitamins – A, D, E, and K. 53 54 Water-Soluble Vitamins • Water-soluble vitamins and/or their derivatives function as coenzymes for enzymes involved in metabolic pathways. • Some fat-soluble vitamins function as hormones, some as anti-oxidants. 55 Thiamine (B1) • The coenzyme form is thiamine pyrophosphate (TPP), which is involved in reactions of energy production. • TPP is a coenzyme for pyruvate dehydrogenase (pyruvate acetyl CoA) and for a TCA cycle enzyme. 56 57 Thiamine Deficiency • Severe deficiency disease is beriberi: characterized by neurological disorders, paralysis, palpitations, cardiomyopathy, muscle atrophy and weakness, loss of weight. • Inhibition of glutamate production and Gamma-aminobutyric acid GABA due to inhibition of the TCA cycle • Severe thiamine deficiency is called Wernicke-Korsakoff syndrome, or Wernicke encephalopathy. • This is characterized by eye muscle weakness, poor muscular coordination (ataxia), loss of memory (amnesia). • Commonly observed in chronic alcholism • If not treated, it can lead to coma and death. 58 Riboflavin (B2) • Riboflavin is a constituent of the coenzymes FAD (flavin adenine dinucleotide) and FMN (flavin mononucleotide). • These coenzymes function as electron carriers for oxidoreductases. • Deficiency thereof is not associated with a major human disease. 59 Niacin (Nicotinic Acid) (B3) • Niacin is a constituent of the coenzymes NAD+ (nicotinamide adenine dinucleotide) and NADP+ (nicotinamide adenine dinucleotide phosphate). • These coenzymes function as electron carriers for oxidoreductases. • Some niacin can be synthesized endogenously from tryptophan--an essential amino acid. 60 Niacin Deficiency • Niacin deficiency disease is pellagra, characterized by dermatitis, dementia, and diarrhea (the three Ds). • Niacin deficiency is also related to ingestion of an unbalanced amino acid mixture containing inadequate tryptophan. 61 Pyridoxine (Vitamin B6) • The coenzyme form is pyridoxal phosphate (PLP). • This coenzyme is required by enzymes involved in amino acid metabolism, such as transaminases. • In the 1960’s, when infants were fed a formula lacking this vitamin, they developed seizures and hyperirritability. • Why? Pyridoxal phosphate is a cofactor involved with the enzyme glutamic acid decarboxylase (GAD), which converts glutamic acid to GABA. • Isoniazid, used in the treatment of TB, can produce a B6 deficiency. • How? • Its metabolites directly attach to and inactivate pyridoxine species. • Second, it directly inhibits the enzyme pyridoxine phosphokinase: • This enzyme activates pyridoxine to pyridoxal 5' phosphate--the cofactor in many "pyridoxine-dependent" reactions. 62 Folic Acid (B9) • The coenzyme form is tetrahydrofolate (FH4) and derivatives. • FH4 functions as a carrier of 1-carbon groups for enzymes catalyzing 1-C transfer reactions. • Tetrahydrofolate derivatives are required for nucleotide synthesis and for the synthesis of methionine from homocysteine. 63 Folate Deficiency • A folate deficiency leads to decreased availability of nucleotides, which will lead to impaired DNA synthesis and cell division. • This impairment in hematopoietic cells accounts for the signs and symptoms of megaloblastic anemia. • During the first few weeks of fetal development will lead to neural tube defects (spina bifida). 64 Folate Deficiency • Megaloblastic anemia is a bone marrow disorder in which normal maturation of rbc’s is impaired, leading to low hemoglobin levels and a high number of megaloblastic cells in the bone marrow. • The red blood cells are macrocytic with fragile membranes. • A folate deficiency also causes homocysteinemia, because FH4 derivative is required to convert homocysteine to methionine. 65 66 Folate Analogs • Folate analogs, like methotrexate (amethopterin), are chemotherapeutic agents. • Folate analogs act as competitive inhibitors of dihydrofolate reductase (FH2 FH4). • This leads to an inhibition of nucleotide synthesis, with a consequent inhibition of DNA synthesis of rapid cell division. 67 68 Vitamin B12 (Cobalamin) • The coenzyme forms are methylcobalamin and deoxyadenosylcobalamin. • A reaction that requires B12 is the conversion of homocysteine to methionine. • Intestinal absorption of B12 requires a glycoprotein called intrinsic factor (IF), which is synthesized in the parietal cells of the stomach. • Large amounts of B12 are stored in the liver. 69 70 B12 Deficiency • The most common disease of B12 deficiency is the disease known pernicious anemia (chronic atrophic gastritis). • Pernicious anemia is caused by an autoimmune disease wherein there is autoimmune destruction of the parietal cells of the stomach. • Lack of IF(intrinsic factor) to B12 deficiency. 71 Pernicious Anemia • Symptoms include megaloblastic anemia and irreversible degeneration of the spinal cord. • Folate recycling is impaired. • Neurological manifestations include paresthesias, difficulty in balance, spastic gait, and dementia. 72 73 Vitamin C (Ascorbate) • Ascorbate is a coenzyme in the hydroxylation of proline and lysine residues in collagen, reactions that are required in the production of mature collagen. • Vitamin C is also an anti-oxidant (reducing agent). • Vitamin C deficiency causes scurvy, which is characterized by bleeding gums, loose teeth, fragile blood vessels, impaired wound healing. 74 Scurvy • Caused by a deficiency of dietary vitamin C associated with malnutrition • Ascorbic acid involved in a variety of biosynthetic pathways • Synthesis of collagen, ascorbic acid is a cofactor for 2 enzymes: prolyl hydroxylase and lysyl hydroxylase • Two enzymes involved in hydroxylation of the proline and lysine amino acids in collagen • Hydroxyproline and hydroxylysine are important for stabilizing collagen by cross-linking in collagen. 76 Fat-Soluble Vitamins • These vitamins are associated with lipids of the diet. • Absorption of these vitamins requires the normal lipid absorption mechanisms, including emulsification by bile, normal mucosal cells, and transport in chylomicrons. 77 Fat-Soluble Vitamins • These vitamins are stored in the body in the liver and adipose tissue. • Some of these vitamins have hormone-like function, some have antioxidant function. 78 Vitamin A • Vitamin A has 3 active forms – retinol, retinal and retinoic acid. • Function: • Important in growth, reproduction, immunity and cell differentiation. • Help maintain healthy bones, skin and mucous membrane. • Visual cycle as a constituent of the visual pigment--rhodopsin. • -carotene from plants is provitamin A – it is converted in the GI tract to retinal. • -carotene functions as an antioxidant. • Animal sources provide vitamin A in the form of retinol and retinyl esters. 79 Vitamin A • They are absorbed and incorporated into chylomicrons. • Stored in the liver as retinyl esters to the tissue. • Delivered to tissue by retinol-binding protein (RBP). • Once delivered to the cell the cell will convert retinol to retinal or retinoic acid. 80 81 Vitamin A • In vision, retinol is carried to the retina and converted to retinal. It then combines with a protein opsin to form a pigment known as rhodopsin. It is an integral part of the visual cycle allowing us to see. • Retinoic acid affects gene expression. It acts like a steroid hormone, binding to retinoid nuclear receptors, and enhancing transcription of certain genes involved in differentiation of stem cell into various cell types. • Both retinol and retinal support sperm production and fertility. • All forms of Vitamin A are essential for proper bone growth. 82 Vitamin A Deficiency • Early symptom is night blindness. This is due to inefficient regeneration of rhodopsin. • Other symptoms include keratinization of epithelium and lack of mucus secretions; susceptibility to infections; drying and keratinization of the cornea (xerophthalmia) causing permanent blindness. • There are pharmacological uses for retinoic acids in the treatment of acne and psoriasis. • Accutane and Retin-A are forms of retinoic acid. 83 Vitamin D • Vitamin D3, cholecalciferol, is from animals (skin UV radiation). • Vitamin D2, ergocalciferol, is from yeast. • The active form of the vitamin is 1,25-dihydroxycholecalciferol, or calcitriol. • Function: • Calcitriol functions in calcium homeostasis primarily. • Also regulates cell differentiation and growth. • Calcitriol functions like a steroid hormone in intestinal mucosal cells, binding to a cytosolic receptor and inducing the synthesis of a calcium binding protein. 84 Vitamin D regulation of Blood Calcium Ultraviolet light causes a form of Cholesterol to be converted to an Inactive form of vitamin D cholecalciferol The liver then converts to 25-hydroxycholecalciferol (calcidiol) Through the action of PTH the Kidneys convert calcidiol to the active form of Vitamin D (calcitriol) Function of calcitriol: • Enhances the absorption of calcium and phosphoru from the small intestines • With PTH stimulates osteoclasts to break down bone and release calcium 86 Vitamin D Deficiency • Rickets, in children, entails improper mineralization of developing bone with resultant formation of weakened, soft pliable bones. Bowing of the legs. • Osteomalacia, in adults, entails demineralization of existing bone, which causes bone to become soft and susceptible to fractures in the hip, spine and other bones. • Osteoporosis, porous bones, is a condition of declining bone quality that impacts millions of Americans. It is progressive of both decline in bone density and strength. 87 Vitamin E • Also called  -tocopherol. • Normally, free radicals are produced to remove unwanted molecules. • Functions as an antioxidant in the blood (LDLs) and in membranes. • It protects membrane phospholipids from attack by reactive oxygen species (ROS). 88 Vitamin K • Vitamin K is required for the post-translational modification of coagulation factors II (prothrombin), VII, IX, and X. • This reaction entails the conversion of glutamate residues on the proteins to  -carboxyglutamate residues by carboxylation. • -carboxyglutamate residues of prothrombin are strong chelators of Ca++, a necessary function in the conversion of prothrombin to thrombin in the 89 90 Vitamin K • Vitamin K deficiency is associated with bleeding disorders. Vitamin K deficiency leads to hypoprothrombinemia. • Vitamin K deficiency is common in newborns, leading to hemorrhagic disease of the newborn. • Vitamin K antagonists are used therapeutically as anticoagulants to treat thromboembolytic disease. Examples are dicumarol and warfarin. 91 92 93 It was a pleasure!!!!