Chapter 26 Nutrition and Metabolism 26 1 Body

Chapter 26: Nutrition and Metabolism 26 -1

Body Weight • Stable with equal energy intake and output – around a homeostatic set point • Determined by combination of environmental and hereditary factors – 30 -50% of variation between individuals due to heredity – rest due to eating and exercise habits 26 -2

Gut-Brain Peptides • Appetite regulators – short term • effects last minutes to hours – long term • effects last weeks to years 26 -3

Short-term Appetite Regulators • Ghrelin – produces hunger • Peptide YY (PYY) – satiety • Cholecystokinin (CCK) – satiety 26 -4

Short-term Appetite Regulators • Ghrelin – hunger – from parietal cells of empty stomach – also stimulates hypothalamus release of human growth hormone releasing hormone 26 -5

Short-term Appetite Regulators • Peptide YY (PYY) – satiety – from enteroendocrine cells in ileum and colon – secreted in proportion to calories consumed – acts as ileal brake • slows stomach emptying 26 -6

Short-term Appetite Regulators • Cholecystokinin (CCK) – satiety – from enteroendocrine cells of duodenum and jejunum – appetite-suppressing effect on brain 26 -7

Long-term Appetite Regulators • Leptin – secreted by adipocytes in proportion to body fat stores • Insulin* – pancreatic beta cells – effect similar to leptin (but weaker) *in addition to stimulating glucose and amino acid uptake, and promotion of glycogen and fat synthesis 26 -8

Hypothalamus • Receptors for gut-brain peptides that regulate release of: 1. neuropeptide Y (hunger) • stimulated by gherlin • inhibited by PYY, leptin, and insulin 2. melanocortin (satiety) • stimulated by leptin, and CCK 26 -9

Appetite Regulation 26 -10

Other Factors in Appetite Regulation • Appetite is briefly satisfied by – chewing – swallowing – stomach filling • Neurotransmitters stimulate desire for different foods – norepinephrine – carbohydrates – galanin – fats – endorphins – protein 26 -11

Calories • One calorie - amount of heat required to raise temperature of 1 g of water 1 °C – 1000 calories is a kilocalorie or Calorie (note that the caloric content listed for foods is in Calories not calories e. g. the Big Xtra with cheese sandwich has 630, 000 calories, 630 Calories) • Fats contain about 9 kcal/g • Carbohydrates and proteins, about 4 kcal/g – sugar and alcohol are “empty” calories -- few nutrients (? ): have the same caloric value as “nutritious” foods • Substance used for fuel is oxidized primarily to 26 -12 make ATP

Nutrients • Ingested chemical used for growth, repair or maintenance • Macronutrients consumed in large amounts – proteins, fats and carbohydrates • Micronutrients needed in small amounts • Recommended daily allowances (RDA) – safe estimate of daily intake for standard needs • Essential nutrients can not be synthesized – minerals, vitamins, 8 amino acids and 1 -3 fatty acids must be consumed in the diet 26 -13

Carbohydrates • Carbohydrates found in 3 places in body – muscle and liver glycogen; blood glucose • Most carbohydrate serves as fuel – neurons and RBCs depend on glucose • Sugars also serve as structural components – nucleic acids, glycoproteins and glycolipids, ATP • Blood glucose carefully regulated by insulin and glucagon 26 -14

RDA and Dietary Sources of Carbs • Carbohydrates are rapidly oxidized, RDA greater than any other nutrient (175 g/day) • Dietary sources: – monosaccharides = glucose, galactose and fructose • liver converts galactose and fructose to glucose – outside hepatic portal system, only blood sugar is glucose – normal blood sugar concentration ranges 70 to 110 mg/d. L – disaccharides = table sugar (sucrose), maltose, lactose – polysaccharides = starch, glycogen and cellulose • Nearly all dietary carbohydrates come from plants 26 -15

Dietary Fiber • Fibrous material that resists digestion • Fiber is important to diet (RDA is 30 g/day) – excess interferes with mineral absorption - iron • Water-soluble fiber (pectin) – blood cholesterol and LDL levels • Water-insoluble fiber (cellulose, lignin) – absorbs water in intestines, softens stool, gives it bulk, speeds transit time 26 -16

Lipids • Average adult male 15% fat; female 25% fat – body’s stored energy • hydrophobic, contains 2 X energy/g compared with carbohydrates, compact storage • glucose and protein sparing (no protein utilized for energy) – fat-soluble vitamins (A, D, E, K) absorbed with dietary fat • ingest less than 20 g/day risks deficiency 26 -17

Functions of Lipids • Diverse functions – structural • phospholipids and cholesterol are components of plasma membranes and myelin – chemical precursors • cholesterol - a precursor of steroids, bile salts and vitamin D • fatty acids - precursors of prostaglandins and other eicosanoids 26 -18

Fat Requirements and Sources • Should be less than 30% of daily calorie intake – typical American gets 40 -50% • Most fatty acids synthesized by body – essential fatty acids must be consumed • Saturated fats – animal origin -- meat, egg yolks and dairy products • Unsaturated fats – found in nuts, seeds and most vegetable oils • Cholesterol – found in egg yolks, cream, shellfish, organ meats and other meats 26 -19

Serum Lipoproteins • Lipids transported in blood as lipoproteins – protein and phospholipid coat around a hydrophobic cholesterol and triglyceride core – soluble in plasma; bind to cells for absorption 26 -20

Serum Lipoproteins • Categorized into 4 groups by density: more protein = higher density – chylomicrons – very low-density (VLDLs) – low-density (LDLs) – high-density (HDLs) 26 -21

Serum Lipoproteins 26 -22

Chylomicrons • Form in absorptive cells of small intestine – enter lymphatic system, then blood – capillary endothelium has lipoprotein lipase to hydrolyze monoglycerides – resulting free fatty acids (FFAs) and glycerol enter fat cells to be resynthesized into triglycerides for storage – chylomicron remnant degraded by liver 26 -23

VLDL and LDL • VLDL – produced by liver to transport lipids to adipose tissue for storage – when triglycerides removed become LDLs (mostly cholesterol) • LDL – absorbed by cells in need of cholesterol for membrane repair or steroid synthesis 26 -24

HDL • Production and function – liver produces an empty protein shell – travels through blood, picks up cholesterol – delivers cholesterol to liver, for elimination in bile 26 -25

Total Cholesterol • Desirable to maintain total cholesterol concentration of < 200 mg/d. L – most cholesterol is endogenous – dietary restrictions lower blood cholesterol levels • by 5% with restriction of dietary cholesterol • by 15 to 20% with restriction of certain saturated fats – vigorous exercise lowers blood cholesterol 26 -26

Desirable Lipoprotein Levels • High levels of HDL – indicate cholesterol is being removed from arteries • Low levels LDL – high LDL correlates with cholesterol deposition in arteries • Recommendations – exercise regularly – avoid smoking, saturated fats, coffee and stress 26 -27

Proteins • 12 -15% of body mass – mostly in skeletal muscles • Functions – muscle contraction • movement of body, cells, cell structures – cell membranes (receptors, cell identity, pumps) – fibrous proteins (collagen, keratin) • structural – globular proteins (antibodies, myoglobin, enzymes) • functional – plasma proteins: blood osmolarity and viscosity 26 -28

Requirements for Protein • RDA - 44 -60 g/day • Nutritional value depends on proportions of amino acids – 8 essential amino acids can not be synthesized • isoleucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine • Cells do not store surplus protein • Complete proteins (dietary) – supply all amino acids in right amount needed to synthesize protein 26 -29

Dietary Sources • Animal proteins (meat, eggs and dairy) are complete proteins – closely match human proteins in amino acid composition • Plant sources must be combined in the right proportions – beans and rice are a complementary choice 26 -30

Nitrogen Balance • Rate of nitrogen ingestion equals rate of excretion – proteins are chief dietary source of nitrogen – excretion chiefly as nitrogenous wastes • Positive nitrogen balance – occurs in children; they ingest more than they excrete – promoted by growth and sex hormones • Negative nitrogen balance – body proteins being broken down for fuel (muscle atrophy) – glucocorticoids promote protein catabolism in states of stress 26 -31

Functions of Minerals • Calcium and phosphorus – bones and teeth • Phosphorus – phospholipids, ATP, CP, buffers, nucleic acids • Calcium, iron, magnesium and manganese – cofactors for enzymes • Iron - essential for hemoglobin and myoglobin • Chlorine - component of stomach acid (HCl) • Mineral salts – electrolytes; govern function of nerve and muscle cells; regulate distribution of body water 26 -32

Dietary Sources of Minerals • Vegetables, legumes, milk, eggs, fish and shellfish • Animal tissues contain large amounts of salt – carnivores rarely lack salt in their diets – herbivores often supplement by ingesting soils • Recommended sodium intake is 1. 1 g/day • Typical American diet contains 4. 5 g/day 26 -33

Vitamins • Body synthesizes some vitamins from precursors – niacin, vitamin A and D – vitamin K, pantothenic acid, biotin, folic acid • produced by intestinal bacteria • Water-soluble vitamins (C, B) – absorbed with water in small intestine; not stored • Fat-soluble vitamins (A, D, E, K) – absorbed with dietary lipids; stored 26 -34

Vitamins 26 -35

Carbohydrate Metabolism • Dietary carbohydrate burned as fuel within hours of absorption (glucose catabolism) C 6 H 12 O 6 + 6 O 2 6 CO 2 + 6 H 2 O • Transfers energy from sugar to ATP 26 -36

Glucose Catabolism • Series of small steps to efficiently transfer energy to ATP (reduces energy lost as heat) • Three major pathways – glycolysis (yields 2 ATP) • glucose (6 C) split into 2 pyruvic acid molecules (3 C) – aerobic respiration (yields 34 -36 ATP) • completely oxidizes pyruvic acid to CO 2 and H 2 O – anaerobic fermentation (if no O 2 available) • pyruvic acid reduced to lactic acid – replenishes NAD+ so glycolysis can continue 26 -37

Overview of ATP Production 26 -38

Overview of ATP Production • NADH releases an electron pair to electron transport system and H+ to prime pumps – enough energy to synthesize 3 ATP • FADH 2 releases its electron pairs further along electron-transport system – enough energy to synthesize 2 ATP • Complete aerobic oxidation of glucose to CO 2 and H 2 O produces 36 -38 ATP – efficiency rating of 40% -- rest is body heat 26 -39

ATP Generated by Oxidation of Glucose 26 -40

Glycogen Metabolism • ATP is quickly used after it is formed -- it is not a storage molecule – extra glucose will not be oxidized, it will be stored • Glycogenesis -- synthesis of glycogen – stimulated by insulin (average adult contains 450 g) • Glycogenolysis -- glycogen glucose – stimulated by glucagon and epinephrine – only liver cells can release glucose back into blood • Gluconeogenesis -- synthesis of glucose from noncarbohydrates, such as fats and amino acids 26 -41

Glucose Storage and Use 26 -42

Lipids • Triglycerides are stored in adipocytes – constant turnover of molecules every 3 weeks • released into blood, transported and either oxidized or redeposited in other fat cells • Lipogenesis = synthesizing fat from other sources – amino acids and sugars used to make fatty acids and glycerol • Lipolysis = breaking down fat for fuel – glycerol is converted to PGAL and enters glycolysis – fatty acids are broken down 2 carbons at a time to produce acetyl-Co. A (beta oxidation) 26 -43

Lipogenesis and Lipolysis Pathways 26 -44

Ketogenesis • Fatty acids catabolized into acetyl groups (by beta-oxidation in mitochondrial matrix) may – enter citric acid cycle as acetyl-Co. A – undergo ketogenesis • metabolized by liver to produce ketone bodies – acetoacetic acid – -hydroxybutyric acid – acetone • rapid or incomplete oxidization of fats raises blood ketone levels (ketosis) and may lead to a p. H imbalance (ketoacidosis) 26 -45

Proteins • Amino acid pool - dietary amino acids plus 100 g of tissue protein broken down each day into free amino acids • May be used to synthesize new proteins • As fuel -- first must be deaminated (removal of NH 2)--what remains is converted to pyruvic acid, acetyl-Co. A or part of citric acid cycle – during shortage of amino acids, the reverse occurs for protein synthesis – the NH 2 become ammonia (NH 3) which is toxic and which the liver converts to urea (excreted in urine) 26 -46

Pathways of Amino Acid Metabolism 26 -47

Urea Synthesis • Liver converts ammonia (NH 3) to urea which is removed from blood by kidneys 26 -48

Absorptive State • Lasts about 4 hours during and after a meal – time of nutrient absorption and use for energy needs • Carbohydrates – blood glucose is available to all cells for ATP synthesis – excess is converted by liver to glycogen or fat • Fats – taken up by fat cells from chylomicrons in the blood – primary energy substrate for liver, fat and muscle cells • Amino acids – most pass through the liver and go onto other cells – in liver cells, may be used for protein synthesis, used for fuel for ATP synthesis or used for fatty acid synthesis 26 -49

Regulation of Absorptive State • Regulated by insulin secreted in response to elevated blood glucose and amino acid levels and the hormones gastrin, secretin and cholecystokinin • Insulin – increases the cellular uptake of glucose by 20 -fold – stimulates glucose oxidation, glycogenesis and lipogenesis but inhibits gluconeogenesis – stimulates active transport of amino acids into cells and promotes protein synthesis • high protein, low carbohydrate meals stimulate release of both insulin and glucagon preventing hypoglycemia 26 -50

Postabsorptive State • Homeostasis of blood glucose critical to brain – when stomach and small intestine are empty- stored fuels are used • Carbohydrates – glucose is drawn from glycogen reserves for up to 4 hours and then synthesized from other compounds • Fat – adipocytes and liver cells convert glycerol to glucose – free fatty acids are oxidized by liver to ketone bodies • other cells use for energy-- leaving glucose for brain • Protein metabolism – used as fuel when glycogen and fat reserves depleted – wasting away occurs with cancer and other diseases 26 -51 from loss of appetite and altered metabolism

Regulation of Postabsorptive State • By sympathetic nervous system and glucagon • Blood glucose drops, glucagon secreted – glycogenolysis and gluconeogenesis raise glucose levels – lipolysis raises free fatty acid levels 26 -52

Regulation of Postabsorptive State • Sympathoadrenal effects – promotes glycogenolysis and lipolysis under conditions of injury, fear, anger and stress – adipose, liver cells and muscle cells are richly innervated and also respond to epinephrine from adrenal medulla – Cortisol from adrenal cortex promotes blood glucose • fat and protein catabolism and gluconeogenesis – Growth hormone – opposes rapid in blood glucose 26 -53

Metabolic Rate • Amount of energy used in the body in a given period of time (kcal/hr or kcal/day) – measured directly in calorimeter (water bath) – measured indirectly by oxygen consumption • Basal metabolic rate (BMR) – relaxed, awake, fasting, room comfortable temperature – adult male BMR is 2000 kcal/day(slightly less female) • Factors affecting total MR – pregnancy, anxiety, fever, eating, thyroid hormones, and depression 26 -54

End 26 -55