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Chapter 25 Metabolism Functions of food source of energy

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1 Chapter 25 Metabolism Functions of food source of energy
essential nutrients stored for future use Metabolism is all the chemical reactions of the body some reactions produce the energy stored in ATP that other reactions consume all molecules will eventually be broken down and recycled or excreted from the body

2 Catabolism and Anabolism
Catabolic reactions breakdown complex organic compounds providing energy (exergonic) glycolysis, Krebs cycle and electron transport Anabolic reactions synthesize complex molecules from small molecules requiring energy (endergonic) Exchange of energy requires use of ATP (adenosine triphosphate) molecule.

3 ATP Molecule & Energy Each cell has about 1 billion ATP molecules that last for less than one minute Over half of the energy released from ATP is converted to heat

4 Energy Transfer Energy is found in the bonds between atoms
Oxidation is a decrease in the energy content of a molecule Reduction is the increase in the energy content of a molecule Oxidation-reduction reactions are always coupled within the body whenever a substance is oxidized, another is almost simultaneously reduced.

5 Mechanisms of ATP Generation
ADP + P = ATP Phosphorylation is bond attaching 3rd phosphate group contains stored energy Mechanisms of phosphorylation within animals substrate-level phosphorylation in cytosol oxidative phosphorylation in mitochondria in chlorophyll-containing plants or bacteria photophosphorylation.

6 Phosphorylation in Animal Cells
In cytoplasm (1) In mitochondria (2, 3 & 4)

7 Carbohydrate Metabolism--In Review
In GI tract polysaccharides broken down into simple sugars absorption of simple sugars (glucose, fructose & galactose) In liver fructose & galactose transformed into glucose storage of glycogen (also in muscle) In body cells --functions of glucose oxidized to produce energy conversion into something else storage energy as triglyceride in fat

8 Fate of Glucose ATP production during cell respiration
uses glucose preferentially Converted to one of several amino acids in many different cells throughout the body Glycogenesis hundreds of glucose molecules combined to form glycogen for storage in liver & skeletal muscles Lipogenesis (triglyceride synthesis) converted to glycerol & fatty acids within liver & sent to fat cells

9 Glucose Movement into Cells
In GI tract and kidney tubules, Na+/glucose symporters Most other cells, GluT facilitated diffusion transporters move glucose into cells insulin increases number of GluT transporters in the membrane of most cells in liver & brain, always lots of GluT transporters Glucose 6-phosphate forms immediately inside cell (requires ATP) thus, glucose hidden in cell Concentration gradient favorable for more glucose to enter

10 Glucose Catabolism Cellular respiration Anaerobic respiration
4 steps are involved glucose + O2 produces H2O + energy + CO2 Anaerobic respiration called glycolysis (1) formation of acetyl CoA (2) is transitional step to Krebs cycle Aerobic respiration Krebs cycle (3) and electron transport chain (4)

11 Glycolysis of Glucose & Fate of Pyruvic Acid
Breakdown of six-carbon glucose molecule into 2 three-carbon molecules of pyruvic acid 10 step process occurring in cell cytosol produces 4 molecules of ATP after input of 2 ATP utilizes 2 NAD+ molecules as hydrogen acceptors If O2 shortage in a cell pyruvic acid is reduced to lactic acid so that NAD+ will be still available for further glycolysis rapidly diffuses out of cell to blood liver cells remove it from blood & convert it back to pyruvic acid

12 Formation of Acetyl Coenzyme A
Pyruvic acid enters the mitochondria with help of transporter protein Decarboxylation pyruvate dehydrogenase converts 3 carbon pyruvic acid to 2 carbon fragment (CO2 produced) pyruvic acid was oxidized so that NAD+ becomes NADH 2 carbon fragment (acetyl group) is attached to Coenzyme A to form Acetyl coenzyme A which enter Krebs cycle coenzyme A is derived from pantothenic acid (B vitamin).

13 Krebs Cycle (Citric Acid Cycle)
Series of oxidation-reduction & decarboxylation reactions occurring in matrix of mitochondria It finishes the same as it starts (4C) acetyl CoA (2C) enters at top & combines with a 4C compound 2 decarboxylation reactions peel 2 carbons off again when CO2 is formed

14 Krebs Cycle Energy stored in bonds is released step by step to form several reduced coenzymes (NADH & FADH2) that store the energy In summary: each Acetyl CoA molecule that enters the Krebs cycle produces 2 molecules of C02 one reason O2 is needed 3 molecules of NADH + H+ one molecule of ATP one molecule of FADH2 Remember, each glucose produced 2 acetyl CoA molecules

15 The Electron Transport Chain
Series of integral membrane proteins in the inner mitochondrial membrane capable of oxidation/reduction Each electron carrier is reduced as it picks up electrons and is oxidized as it gives up electrons Small amounts of energy released in small steps Energy used to form ATP by chemiosmosis

16 Chemiosmosis Small amounts of energy released as substances are passed along inner membrane Energy used to pump H+ ions from matrix into space between inner & outer membrane High concentration of H+ is maintained outside of inner membrane ATP synthesis occurs as H+ diffuses through a special H+ channel in inner membrane

17 Steps in Electron Transport
Carriers of electron transport chain are clustered into 3 complexes that each act as proton pump (expel H+) Mobile shuttles pass electrons between complexes Last complex passes its electrons (2H+) to a half of O2 molecule to form a water molecule (H2O)

18 Proton Motive Force & Chemiosmosis
Buildup of H+ outside the inner membrane creates + charge electrochemical gradient potential energy is called proton motive force ATP synthase enzyme within H+ channel uses proton motive force to synthesize ATP from ADP and P

19 Summary of Cellular Respiration
Glucose + O2 is broken down into CO2 + H2O + energy used to form 36 to 38 ATPs 2 ATP are formed during glycolysis 2 ATP are formed by phosphorylation during Krebs cycle electron transfers in transport chain generate 32 or 34 ATPs from one glucose molecule Summary in Table 25.1 Points to remember ATP must be transported out of mitochondria in exchange for ADP uses up some of proton motive force Oxygen is required or many of these steps can not occur

20 Carbohydrate Loading Long-term athletic events (marathons) can exhaust glycogen stored in liver and skeletal muscles Eating large amounts of complex carbohydrates (pasta & potatoes) for 3 days before a marathon maximizes glycogen available for ATP production Useful for athletic events lasting for more than an hour

21 Glycogenesis & Glycogenolysis
glucose storage as glycogen 4 steps to glycogen formation in liver or skeletal muscle stimulated by insulin Glycogenolysis glucose release not a simple reversal of steps enzyme phosphorylase splits off a glucose molecule by phosphorylation to form glucose 1-phosphate enzyme only in hepatocytes so muscle can’t release glucose enzyme activated by glucagon (pancreas) & epinephrine (adrenal)

22 Gluconeogenesis Liver glycogen runs low if fasting, starving or not eating carbohydrates forcing formation from other substances lactic acid, glycerol & certain amino acids (60% of available) Stimulated by cortisol (adrenal) & glucagon (pancreas) cortisol stimulates breakdown of proteins freeing amino acids thyroid mobilizes triglycerides from adipose tissue

23 Transport of Lipids by Lipoproteins
Most lipids are nonpolar and must be combined with protein to be tranported in blood Lipoproteins are spheres containing hundreds of molecules outer shell polar proteins (apoproteins) & phospholipids inner core of triglyceride & cholesterol esters Lipoprotein categorized by function & density 4 major classes of lipoproteins chylomicrons, very low-density, low-density & high-density lipoproteins

24 Classes of Lipoproteins
Chylomicrons (2 % protein) form in intestinal epithelial cells to transport dietary fat apo C-2 activates enzyme that releases the fatty acids from the chylomicron for absorption by adipose & muscle cells liver processes what is left VLDLs (10% protein) transport triglycerides formed in liver to fat cells LDLs (25% protein) --- “bad cholesterol” carry 75% of blood cholesterol to body cells apo B100 is docking protein for receptor-mediated endocytosis of the LDL into a body cell if cells have insufficient receptors, remains in blood and more likely to deposit cholesterol in artery walls (plaque) HDLs (40% protein) --- “good cholesterol” carry cholesterol from cells to liver for elimination

25 Blood Cholesterol Sources of cholesterol in the body
food (eggs, dairy, organ meats, meat) synthesized by the liver All fatty foods still raise blood cholesterol liver uses them to create cholesterol stimulate reuptake of cholesterol containing bile normally lost in the feces Desirable readings for adults total cholesterol under 200 mg/dL; triglycerides mg/dL LDL under 130 mg/dL; HDL over 40 mg/dL cholesterol/HDL ratio above 4 is undesirable risk Raising HDL & lowering cholesterol can be accomplished by exercise, diet & drugs

26 Fate of Lipids Oxidized to produce ATP
Excess stored in adipose tissue or liver Synthesize structural or important molecules phospholipids of plasma membranes lipoproteins that transport cholesterol thromboplastin for blood clotting myelin sheaths to speed up nerve conduction cholesterol used to synthesize bile salts and steroid hormones.

27 Lipid Anabolism: Lipogenesis
Synthesis of lipids by liver cells = lipogenesis from amino acids converted to acetyl CoA & then to triglycerides from glucose from glyceraldehyde 3-phosphate to triglycerides Stimulated by insulin when eat excess calories

28 Ketosis Blood ketone levels are usually very low
many tissues use ketone for ATP production Fasting, starving or high fat meal with few carbohydrates results in excessive beta oxidation & ketone production acidosis (ketoacidosis) is abnormally low blood pH sweet smell of ketone body acetone on breath occurs in diabetic since triglycerides are used for ATP production instead of glucose & insulin inhibits lipolysis

29 Fate of Proteins Proteins are broken down into amino acids Usage
transported to the liver Usage oxidized to produce ATP used to synthesize new proteins enzymes, hemoglobin, antibodies, hormones, fibrinogen, actin, myosin, collagen, elastin & keratin excess converted into glucose or triglycerides no storage is possible Absorption into body cells is stimulated by insulinlike growth factors (IGFs) & insulin

30 Protein Catabolism Breakdown of protein into amino acids
Liver cells convert amino acids into substances that can enter the Krebs cycle deamination removes the amino group (NH2) converts it to ammonia (NH3) & then urea urea excreted in the urine Converted substances enter the Krebs cycle to produce ATP

31 Protein Anabolism Production of new proteins by formation of peptide bonds between amino acids 10 essential amino acids are ones we must eat because we can not synthesize them nonessential amino acids can be synthesized by transamination (transfer of an amino group to a substance to create an amino acid) Occurs on ribosomes in almost every cell Stimulated by insulinlike growth factor, thyroid hormone, insulin, estrogen & testosterone Large amounts of protein in the diet do not cause the growth of muscle, only weight-bearing exercise

32 Phenylketonuria (PKU)
Genetic error of protein metabolism that produces elevated blood levels of amino acid phenylalanine causes vomiting, seizures & mental retardation normally converted by an enzyme into tyrosine which can enter the krebs cycle Screening of newborns prevents retardation spend their life with a diet restricting phenylalanine restrict Nutrasweet which contains phenylalanine

33 Metabolic Adaptations
Absorptive state nutrients entering the bloodstream glucose readily available for ATP production 4 hours for absorption of each meal so absorptive state lasts for 12 hours/day Postabsorptive state absorption of nutrients from GI tract is complete body must meet its needs without outside nutrients late morning, late afternoon & most of the evening assuming no snacks, lasts about 12 hours/day more cells use ketone bodies for ATP production maintaining a steady blood glucose level is critical

34 Metabolism During Fasting & Starvation
Fasting means going without food for hours/days Starvation means weeks or months can survive 2 months or more if drink enough water amount of adipose tissue is determining factor Nutritional needs nervous tissue & RBC need glucose so amino acids will be broken down for gluconeogenesis blood glucose stabilizes at 65 mg/100 mL lipolysis releases glycerol used in gluconeogenesis increase in formation of ketone bodies by liver cells due to catabolism of fatty acids by 40 days, ketones supply 2/3’s of brains fuel for ATP

35 Absorption of Alcohol Absorption begins in the stomach but is absorbed more quickly in the small intestine fat rich foods keep the alcohol from leaving the stomach and prevent a rapid rise in blood alcohol a gastric mucosa enzyme breaks down some of the alcohol to acetaldehyde Females develop higher blood alcohols have a smaller blood volume have less gastric alcohol dehydrogenase activity

36 Metabolic Rate Rate at which metabolic reactions use energy
energy used to produce heat or ATP Basal Metabolic Rate (BMR) measurements made under specific conditions quiet, resting and fasting condition Basal Temperature maintained at 98.6 degrees shell temperature is usually 1 to 6 degrees lower

37 Heat Production Factors that affect metabolic rate and thus the production of body heat exercise increases metabolic rate as much as 15 times hormones regulate basal metabolic rate thyroid, insulin, growth hormone & testosterone increase BMR sympathetic nervous system’s release of epinephrine & norepinephrine increases BMR higher body temperature raises BMR ingestion of food raises BMR 10-20% children’s BMR is double that of an elderly person

38 Mechanisms of Heat Transfer
Temperature homeostasis requires mechanisms of transferring heat from the body to the environment conduction is heat exchange requiring direct contact with an object convection is heat transfer by movement of gas or liquid over body radiation is transfer of heat in form of infrared rays from body evaporation is heat loss due to conversion of liquid to a vapor (insensible water loss)

39 Hypothalamic Thermostat
Preoptic area in anterior hypothalamus receives impulses from thermoreceptors generates impulses at a higher frequency when blood temperature increases impulses propagate to other parts of hypothalamus heat-losing center heat-promoting center Set in motion responses that either lower or raise body temperature

40 Thermoregulation Declining body temperature
thermoreceptors signal hypothalamus to produce TRH TRH causes anterior pituitary to produce TSH resulting in vasoconstriction in skin adrenal medulla stimulates cell metabolic rate shivering release of more thyroid hormone raises BMR Increases in body temperature sweating & vasodilation

41 Hypothermia Lowering of core body temperature to 35°C (95°F) Causes
immersion in icy water (cold stress) metabolic diseases (hypoglycemia, adrenal insufficiency or hypothyroidism) drugs (alcohol, antidepressants, or sedatives) burns and malnutrition Symptoms that occur as body temperature drops shivering, confusion, vasoconstriction, muscle rigidity, bradycardia, acidosis, hypoventilation, coma & death

42 Regulation of Food Intake
Hypothalamus regulates food intake feeding (hunger) center satiety center Stimuli that decrease appetite glucagon, cholecystokinin, epinephrine, glucose & leptin stretching of the stomach and duodenum Signals that increase appetite growth releasing hormone, opioids, glucocorticoids, insulin, progesterone & somatostatin

43 Guidelines for Healthy Eating
Nutrients include water, carbohydrates, lipids, proteins, vitamins and minerals Caloric intake women 1600 Calories/day is needed active women and most men 2200 Calories teenage boys and active men 2800 calories Food guide pyramid developed by U.S. Department of Agriculture indicates number of servings of each food group to eat each day

44 Food Guide Pyramid

45 Minerals Inorganic substances = 4% body weight Functions
calcium & phosphorus form part of the matrix of bone help regulate enzymatic reactions calcium, iron, magnesium & manganese magnesium is catalyst for conversion of ADP to ATP form buffer systems regulate osmosis of water generation of nerve impulses

46 Vitamins Organic nutrients needed in very small amounts
serve as coenzymes Most cannot be synthesized by the body Fat-soluble vitamins absorbed with dietary fats by the small intestine stored in liver and include vitamins A, D, E, and K Water-soluble vitamins are absorbed along with water in the Gl tract body does not store---excess excreted in urine includes the B vitamins and vitamin C

47 Antioxidant Vitamins C, E and beta-carotene (a provitamin)
Inactivate oxygen free radicals highly reactive particles that carry an unpaired electron damage cell membranes, DNA, and contribute to atherosclerotic plaques arise naturally or from environmental hazards such as tobacco or radiation Protect against cancer, aging, cataract formation, and atherosclerotic plaque

48 Vitamin and Mineral Supplements
Eat a balanced diet rather than taking supplements Exceptions iron for women with heavy menstrual bleeding iron & calcium for pregnant or nursing women folic acid if trying to become pregnant reduce risk of fetal neural tube defects calcium for all adults B12 for strict vegetarians antioxidants C and E recommended by some

49 Fever Abnormally high body temperature
toxins from bacterial or viral infection = pyrogens heart attacks or tumors tissue destruction by x-rays, surgery, or trauma reactions to vaccines Beneficial in fighting infection & increasing rate of tissue repair during the course of a disease Complications--dehydration, acidosis, & brain damage.

50 Obesity Body weight more than 20% above desirable standard
Risk factor in many diseases cardiovascular disease, hypertension, pulmonary disease, non-insulin dependent diabetes mellitus arthritis, certain cancers (breast, uterus, and colon), varicose veins, and gallbladder disease.

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