Metabolism and Energy Balance: Distribution and Use of Energy in Humans

1. Chapter 22 Metabolism and Energy Balance

2. About this Chapter • How energy is distributed and used in humans • How nutrients are converted to the energy and building blocks for synthesis • How hormones control metabolic processes • How the body maintains a constant temperature

3. Body Energy: Eating Controls • Cortex – "hunger" • CNS Feeding center • CNS satiety center • CNS & GI peptides • Ghrelin • Leptin • Peptide YY • Insulin • CCK • CRH • Neuropeptide Y

8. Body Energy: Input = Output (+ storage) • Energy for temperature regulation – heat • Energy for metabolic processes – work • Transport work – move molecules • Mechanical work – muscle contraction • Chemical work – synthesis & storage • Energy use is measured by oxygen consumption • Calories in food (kilocalorie = 1L H2O 1˚C)

9. Respiratory Quotient • RQ= The ratio of Pure CO2 produced to O2 consumed • For Pure Carbohydrate Catabolism: RQ= 1.0 • For Pure Protein Catabolism: RQ= 0.8 • For Pure Fat Catabolism: RQ= 0.7

10. Respiratory Quotient • Carbohydrates: The respiratory quotient for carbohydrate metabolism can be demonstrated by the chemical equation for oxidation of glucose: • C6H12O6 + 6 O2 → 6 CO2+ 6 H2O • Because the gas exchange in this reaction is equal, the respiratory quotient for carbohydrates is: RQ = 6 CO2 / 6 O2 = 1.0 • Fats: The chemical composition of fats differs from that of carbohydrates in that fats contain considerably fewer oxygen atoms in proportion to atoms of carbon and hydrogen. The substrate utilization of palmitic acid is: • C16H32O2 + 23 O2 → 16 CO2 + 16 H2O • Thus, the RQ for palmitic acid is approximately 0.7. RQ = 16 CO2 / 23 O2 = 0.696 • Proteins: The respiratory quotient for protein metabolism can be demonstrated by the chemical equation for oxidation of albumin: • C72H112N18O22S + 77 O2 → 63 CO2 + 38 H2O + SO3 + 9 CO(NH2)2 • The RQ for protein is approximately 0.8. RQ = 63 CO2/ 77O2 = 0.8 • Due to the complexity of the various ways in which different amino acids can be metabolized, no single RQ can be assigned to the oxidation of protein in the diet; however, 0.8 is a frequently utilized estimate.

11. Changes in Metabolic Rate • Basal metabolic rate (BMR) • Modifying factors • Age & gender • Lean muscle mass • Physical activity level • Diet • Hormones

12. Basal Metabolism In their review, Rolfe and Brown (1997) concluded that • ∼10% of the oxygen consumed during BMR is consumed by nonmitochondrial processes, • ∼20% is consumed by mitochondria to counteract the mitochondrial proton leak, and • the remaining 70% is consumed for mitochondrial ATP production. At a whole-animal level, ATP production can be divided into • 20%–25% for Na+,K+-ATPase activity, • 20%–25% for protein synthesis, ∼ • 5% for Ca2+-ATPase activity, • ∼7% for gluconeogenesis, • ∼2% for ureagenesis, • ∼11% for all other ATP-consuming processes. These estimates are averages over the entire animal, and the relative contribution of the different processes varies between tissues. For example, it is estimated that although Na+,K+-ATPase activity constitutes only ∼10% of cellular energy turnover in the liver, it is responsible for ∼60% in brain and kidney (Clausen et al. 1991). It can be seen from these estimates that membrane-associated activities constitute a significant portion of resting metabolic activity (and thus BMR) in higher animals.

15. Summary of Metabolic Conversions of Nutrients • Nutrients are used, or stored • In general glucose, fats & AAs can be interconverted

16. Summary of Metabolic Conversions of Nutrients Figure 22-2: Summary of metabolism

17. Metabolic Proscesses: Reversible Conversions • Glycogenesis (glucose to glycogen) • Glycogenolysis (glycogen to glucose) • Gluconeogenesis (amino acids to glucose) • Lipogenesis (glucose or FFAs to fats) • Lipolysis (fats to FFAs & glycerol)

18. Metabolic Energy Production: Review & Overview • Reactants: glucose • Glycogen, FFAs • Amino acids • Phosphoylation • Glycolysis–cytoplasm • 2 ATPs, anaerobic • Citric Acid Cycle-2 ATPs, mitochondria, aerobic • Electron Transport system • High energy e-,  32 ATPs

19. Metabolic Energy Production: Review & Overview Figure 22-3: Summary of biochemical pathways for energy production

20. “Fed State” or Absorptive Metabolism: Anabolic Processes • Reversible pathways shift to anabolic processes • Carbohydrates energize synthesis & storage • Amino Acids built into proteins, surplus stored

21. “Fed State” or Absorptive Metabolism: Anabolic Processes Figure 22-4: 4 Dual (push-pull) control of metabolism

22. Fat Metabolism: Long Term Nutrient Storage • In adipose cells • In blood: HDL, LDL • FFAs, cholesterol • (plaque build up) • Conversion in liver • Excreted in bile • Used for energy & synthesis

23. Fat Metabolism: Long Term Nutrient Storage Figure 22-5: Transport and fate of dietary fats

24. “Fasted State” or Post-Absorptive Metabolism: Catabolic • Pathways shift to maintain energy for metabolism • Storage  glucose in blood  organs in need

25. “Fasted State” or Post-Absorptive Metabolism: Catabolic Figure 22-6: Fasted-state metabolism

26. Pancreatic Hormones, Insulin & Glucagon Regulate Metabolism • Beta cells produce insulin – cellular uptake of blood glucose • Alpha cells produce glucagon –  blood glucose (from cells) • D cells produce somatostatin –  gastric secretion

27. Pancreatic Hormones, Insulin & Glucagon Regulate Metabolism Figure 22-7 b: The endocrine pancreas

28. Pancreatic Hormones, Insulin & Glucagon Regulate Metabolism Figure 22-8: Metabolism is controlled by insulin and glucagon

29. Lipohypertrophy in a Patient • A 55-year-old man with a 31-year history of type 1 diabetes mellitus presented for a routine clinical evaluation, his first in two decades. His insulin regimen consisted of a combination of neutral protamine Hagedorn (NPH) and rapid-acting insulin. In the many years since his diabetes diagnosis, he had habitually injected insulin into two locations in the periumbilical region. Two discrete subcutaneous masses were palpated. Both masses were firm and pendulous. A clinical diagnosis of insulin-induced lipohypertrophy was made. This condition has been documented with many insulin preparations. Careful attention should be paid to the teaching of correct methods of insulin injection, site rotation, and routine inspection of injection sites. Lipohypertrophy can be associated with glycemic flux and can be disfiguring. The patient was counseled regarding injection-site rotation and encouraged to use a 6-mm rather than an 8-mm needle. NPH was replaced with insulin glargine. The patient was subsequently lost to follow-up.

31. Insulin Action on Cells: Dominates in Fed State Metabolism •  glucose uptake in most cells • (not active muscle) •  glucose use & storage •  protein synthesis •  fat synthesis

32. Insulin Action on Cells: Dominates in Fed State Metabolism Figure 22-10: Insulin’s cellular mechanism of action

34. Insulin: Summary and Control Reflex Loop Figure 22-13: Fed-state metabolism

38. Relationship between HbA1c and average finger blood glucose HbA1c of 9% = 260 mg/dl (14.4 mmol/l) HbA1c of 8% = 220 “ (12.2 “ ) HbA1c of 7% = 180“ (10.0 “ ) HbA1c of 6% = 140“ (7.7 “ ) HbA1c of 5% = 100“ (5.5 “ )

39. Glucagon Action on Cells: Dominates in Fasting State Metabolism • Glucagon prevents hypoglycemia by  cell production of glucose • Liver is primary target to maintain blood glucose levels

40. Glucagon Action on Cells: Dominates in Fasting State Metabolism Figure 21-14: Endocrine response to hypoglycemia

41. Diabetes Mellitus: Abnormally Elevated Blood Glucose (Hyperglycemia) • Type 1: beta cells destroyed- no insulin producedchronic fasted state, "melting flesh", ketosis, acidosis, glucosurea, diuresis & coma

42. Diabetes Mellitus: Abnormally Elevated Blood Glucose (Hyperglycemia) Figure 22-15: Acute pathophysiology of type 1 diabetes mellitus

43. Diabetes Mellitus: Type II a Group of Diseases • Over 15 million diabetics in USA- 10% type I, 90% type II • Insulin resistance keeps blood glucose too high • Problem with receptors, glucagons levels • Chronic complications: atherosclerosis, renal failure& blindness

45. Diabetes Mellitus: Type II a Group of Diseases Figure 22-16: Normal and abnormal glucose tolerance tests

46. Energy Balance: About 50% used for Body Heat Figure 22-17: Energy balance

47. Body Temperature Balance: Homeothermic • Metabolic heat production usually required to maintain balance • Balance is very narrow range, usually higher than environment

48. Body Temperature Balance: Homeothermic Figure 22-18: Heat balance

49. Thermoregulation: Homeostatic Balancing of Body Temperature • Peripheral and body core receptors – senses change • Hypothalamic thermoregulatory center – integrates & initiates: • Shivering, non-shivering thermogenesis, vasoconstriction

50. Thermoregulation: Homeostatic Balancing of Body Temperature Figure 22-19: Thermoregulatory reflexes