MCB 135E Discussion

1. MCB 135E Discussion GSI: Jason Lowry Dec. 9, 2004

2. Topics • Muscle Growth and Plasticity • Nutrition • Eating Disorders • Homeostasis • Hormesis

3. Muscle Growth and Plasticity • What are the major components of muscle? • From what embryologic layer are muscles derived? • Which kinds of muscles are under autonomic control? Which are under voluntary control? • What kind of neuron innervates muscle and causes it to contract? • What specialized oxygen-carrying molecule is found in muscle?

4. Embryology • All muscles derive from the MESODERM of the GASTRULA Remember? Morula then Blastula then Gastrula • From its mesoderm layer: A) striated or voluntary muscles B) cardiac muscle or scalariform C) smooth muscle (of GI tract, Urinary, etc)

6. Importance of the Nervous System • Autonomic nervous system controls smooth and cardiac muscles • Central nervous system controls the voluntary muscles

8. Histology Each fiber being a multinucleated cell consists of myofibrils in bundles with a large number of mitochondria and a myoglobin (pigmented protein)

9. Muscle Growth and Plasticity • What are the main proteins of the myofibril unit? • Know the characteristics of the two main muscle fiber types. • What is myoplasticity? • From what molecule does muscle obtain ATP for contraction? Under what conditions might lactate be produced? Under what conditions is the TCA cycle used to produce ATP?

10. Contractility Secondary to the sliding characteristic of the 2 main proteins of the myofibrils: MYOSIN ACTIN (thinner)

11. Steps in Contraction 1. Discharge of motor-neuron at the myo-neural plate with release of the neurotransmitter acetylcholine (Ach) 2. The binding of Ach to its receptors increases Na+ and K+ conductance, generating an action potential 3. The sarcoplasmic reticulum releases Ca++, activating the enzyme troponin, which uncovers the myosin binding sites allowing cross-linkages between actin and myosin to form Steps in Relaxation Ca++ pumped back in the sarcoplasmic reticulum, and the release of Ca++ from the troponin induces cessation of interaction between actin and myosin.

12. THE FUEL GLUCOSE, 6 carbon (C) compound, enters the muscle +/- insulin Broken into 3C compound: Lactate and Pyruvate Lactate to pyruvate and/or back to circulation for gluconeogenesis

14. Muscle Growth and Plasticity • How does muscle change after development? Do we make new muscle cells? If not, then how do our muscles become bigger with use? • What kinds of exercise lead to an increase in cross-sectional area of muscle fibers? What kinds of exercise increase the level of oxidative metabolism?

15. TYPES of FIBERS Type 1: reddish Slow Oxidative (SO) Type 2: pale and divided into Fast Oxidative Glycolytic (FOG) Fast Glycolytic (FG)

16. The number and type of fibers is dictated by genetic determinants but ……..ALAS!!! Appropriate stimulations may induce an almost complete change Hence….. MYOPLASTICITY

17. Myoplasticity: Concept Ability of the muscle to alter the quantity and the type of its proteins in response to stimulations Modalities of stimulations: 1) Physical activities leading to an increase in its cross-sectional area 2) Increase in the muscular mass with changes in the myosin type Muscle plasticity may involve: • Change in the amount of protein • Change in the type of protein • Combination of both

18. Myoplasticity Due to Exercise • Endurance exercise increases the oxidative metabolism of the muscle • Resistance training increases the cross-sectional area due to true hypertrophy of the single cells • Inactivity induces rapid regression

19. Muscle Fiber Number Virtually Fixed at Birth • The increase in mass (hypertrophy, sometimes as much as 50%) is due to increase in length and in the cross-sectional area of the muscle fibers. This is due to an increase in the number of myofibrils (from 75 to over 1000) • The capacity for regeneration and plasticity is a response to neural, hormonal and nutritional differences

20. Nutrition • What are the stimulators of appetite? • What the depressors of appetite? • What is the sense of satiety? What are its inducers? • Why does it make sense for high insulin levels to stimulate hunger? • What kind of cell secretes leptin? Why does it make sense for this cell type to secrete a depressor of hunger?

21. Nutrition • What is the basal requirement of nutrients for an very active adolescent or adult? • How many Kcal are there in 1 gm of fat? in 1 gm of protein? in 1 gm of carbohydrate? • What features of our intestinal tract point towards our being omnivores? • Why is it that water is so important? • What form must carbohydrates be in to be absorbed through the intestinal wall?

22. Supply of Calories • From ATP = 1 kcal (walk 10 meters) • From CP = 10 kcal (walk 100 meters) • From blood glucose = 80 kcal • From liver glycogen = 400 kcal • From muscle glycogen = 1600 kcal All of the above enough for a marathon! • Lipids only a very slow turnover to energy • Proteins a very very slow turnover to energy

23. Caloric production • FATS : 1 gm = 9 kcal • PROTEINS : 1 gm = 4 kcal • CHO : 1 gm = 4 kcal

24. The Caloric Requirement 1. The calorie and the kilocalorie 2. The basal requirement = 1600 kcal 3. Requirements for moderately active adult 1800 2200 kcal 4. For a very active adolescent or adult: 3000 kcal or more 5. Memo the THYROID EFFECT !!!!

25. Nutrition • What is the minimum safe percentage of protein in an adult diet? Why is it dangerous to take in less? • What two vitamin levels should be checked with frequency in a vegan diet to ensure adequate intake? • What kinds of fat are best for us to take in? What is one solid fat that is good for us?

26. The Macronutrients: Lipids • Saturated, no double bonds, usually solid • Trans-fats, from liquid to solid format (usually commercial only) • Mono-unsaturated, like olive oil • Poly-unsaturated, like most other oils • OMEGA 3, fatty acids, like many fish oils

27. The Macronutrients: Proteins • Protein intake at least 11-12% of the total • Intakes below 8.7% carry severe risk of serious deficits

30. Nutrition • What are the micronutrients? • Why do we need fiber in our diets? • Has caffeine been shown to be bad for the average person?

31. The Micronutrients • Salt, Na+ (<5 mg/day) and K+ (deficits, excesses, need) • Ca+ (1800 mg/day), P and Fl (bone metabolism) • Fe++ (deficit and excess), Cu, Mn, and Mg • Other metals: Cr, Se, Zn and the Metalloid I • Memo the hidden aspects of hypothyroidism

32. RDA/ day(for some components) Ca++ : 1800 mg or more P : 1200 mg Fe++ : 10-12 mg I : 150 g Se : 45-50 g

33. The Macronutrients: Fibers • High risk for the “vegans” • Benefits and risk of the fibers • The good and the not so good vegetables • CONCLUSION: long live the Mediterranean diet but….with some cracks!!!

34. Addicting Substances Coffee and Tea (caffeine and teine) Memo: aminophylline and brochospasm ALCOHOLIC BEVERAGES!!! The benefits and the……. Disasters!!!!

35. Stress: Homeostasis • What does the term "homestasis" mean? • What does the term "allostasis" mean? • What is the General Adaptation Syndrome? How might the ideas of the adaptation syndrome be applied to developmental periods?

36. Stress, Homeostasis, and Allostasis An organism must vary all parameters of its internal milieu and match them appropriately to environmental demands through: Homeostasis: steady state and optimal set-points are achieved; it is obtained by repeated fluctuation s of various physiological systems (allostasis) and/or long-term exposure to elevated levels of physiologic activity Allostasis: emphasis is on optimal operating ranges of physiologic systems; it represents stability obtained through change Allostatic load: the cumulative, multi-system view of physiologic toll that may be exacted on the body through attempts at adaptation

37. Stress: Hormesis • What types of physical stress affect cortisol secretion? What types of psychological stress? • What role does stress play in longevity • Why do we get sick when we are stressed?

38. Hormesis • Hormesis: the beneficial action (s) resulting from the response of an organism to a low-intensity stressor • The term “Hormesis” was first utilized by T. D. Luckey in 1991 in a book entitled Radiation Hormesis. • High doses of radiation increase mortality and shorten life; small doses of radiation prolong life (as compared to the non-irradiated animals).

39. Hormesis & Chaperones • The beneficial effects of moderate stress on the resistance to extreme and prolonged stresses, and the promotion of longevity, may be due to their action in stimulating the production of “heat-shock proteins” (HSP) (also known as “stress proteins”). • HSP are a type of “chaperone” protein • Chaperones ubiquitin, glucose related proteins, endoplasmic reticulum chaperones.

40. Hormesis & Chaperones • During stress, HSP level increases and protects the normal assembly of proteins by promoting their appropriate folding • In C. Elegans it has been shown that upon stress, there is increase levels of HSP together with a longer life.

41. However, there is no such thing as a “free meal” Increased longevity is associated with unwanted effects on growth, fertility, length of development, metabolic rate, etc.

42. Stress • What is the difference between a specific and a nonspecific response to stress? Give an example of each. • Know the features of the fight/flight response. • What bodily functions are inhibited by stress? Stimulated? • What happens to the immune system during prolonged stress?

43. Stress induces defense mechanisms for maintenance of homeostasis in response to environmental challenges Types of stress known to stimulate the HPA axis*: Physical Stress:hypoglycemia, trauma, exposure to extreme temperatures, infections, heavy exercise Psychological Stress: Acute anxiety, Anticipation of stressful situations, Novel situations, Chronic anxiety Exposure to stress generates: Specific responses: varying with the stimulus and generating different responses with each stimulus Non-Specific responses:always the same, regardless of the stimulus and mediated through stimulation of neural, endocrine & immune axes *HPA axis = hypothalamo-pituitary-adrenal axis Some Characteristics of Stress

44. “Fright, Flight, or Fight” Responses to Stress • Increased blood pressure • Increased heart rate • Increased force of heart contraction • Increased heart conduction velocity • Shift of blood flow distribution • Away from the skin and splachnic regions • And more to heart, skeletal muscle, and brain • Contraction of spleen capsule • Increased depth and rate of respiration • Mobilization of liver glycogen to glucose (glycogenolysis) • Mobilization of free fatty acids from adipose tissue (lipolysis) • Mydriasis (widening of pupil) • Accommodation for far vision (relaxation of ciliary muscle) • Widening of palpebral fissure (eyelids wide open) • Piloerection • Inhibition of gastrointestinal motility and secretion, contraction of sphincters • Sweating (cold sweats as skin blood vessels are constricted).

45. Pathophysiologic Responses During and After Stress During Stress Energy storage ceases because: Sympathetic activity Parasympathetic activity Insulin secretion Access to energy storage is facilitated & energy storage steps are reversed: glucocorticoid secretion Epinephrine/norepinephrine secretion Glucagon secretion After Stress If physiologic responses are insufficient and adaptation is incomplete, symptoms of poor health are registered (e.g. loss of energy when freeing energy from storage and returning to storage) Examples of consequences: Muscle wasting, Diabetes (Type 2), ulcers, colitis, diarrhea Inhibition of growth (in childhood), Osteoporosis (in old age) LHRH, testosterone