Chapter 11: Metabolism - Powerpoint

where is the feeding/satiety center in the brain?

hypothalamus

what is thee glucostatic theory?

relies on blood \[glucose\] levels to stimulate or inhibit the feeding/satiety centers

→ has a short term effect

→ decrease glucose = stimulate feeding and inhibit satiety

→ increase glucose = inhibit feeding and stimulate satiety

what is the lipostatic theory?

relies on lipid and adipose tissue to stimulate or inhibit the feeding/satiety centers

→ has a long term effect as it pulls from storage

→ increase production of leptin hormone = inhibit neuropeptide Y release = decrease stimulation of feeding/satiety center

→ the more fat in storage, the more leptin that is produced

how does the stomach influence feeding and satiety?

it secretes the hormone ghrelin which increases feeling of hunger and stimulates growth hormone release

how does the duodenum influence feeding and satiety?

it secretes CCK and GLP-1 to decrease feelings of hunger

what are other factors that influence feeding and satiety?

→ eating and chewing, gut distension

→ sight, smell, taste

→ cravings: physiological and psychological

what is the mass balance of energy equation?

total body energy = energy stored + energy in - energy out

what is energy stored?

it is the energy that is not needed for immediate work

→ glycogenesis

→ lipogenesis

what is glycogenesis?

the production of glycogen

→ 1 glycogen can contain 55,000 glucose molecules

→ liver can store 100g and skeletal muscle can store 200g

→ **taking out of glucose nutrient pool and into glycogen stores**

what is lipogenesis?

the production of lipids

→ from subcutaneous and abdominal adipose tissue

what is energy in?

it is the food we consume where potential energy is stored in chemical bonds

→ good calorimetry measures the energy in food

→ direct calorimetry measures heat production

→ measured in kilocalories (kcal) = Calorie (C) = 1000 calories

what is energy out?

it is the work + heat production

→ work

→ metabolism

→ metabolic rates: BMR, RMR, MR

what is work?

it is the things that we do on cellular and body levels

→ **transport**: between compartments and within cells

→ **mechanical**: internal work within cells, heart beats, external work of movemennt

→ **chemical**: storage of energy in chemical bonds

what is metabolism?

it is the energy used by the body

→ measured using indirect calorimetry

→ **metabolic rate (kcal/day) = L O2 consumed/day x 4.825 kcal/L O2**

what is basal metabolic rate (BMR)?

the lowest amount of energy required by the body to stay alive

→ kcal/day or cal/hr

what is resting metabolic rate (RMR)?

close approximation of BMR measured at rest, after 12 hr fast and at a comfortable temperature

→ kcal/day or cal/hr

→ thermoneutral: not using energy to warm/cool the body (82-86 degrees F)

what is metabolic rate (MR)?

energy expenditure at any time

→ BMR + any activity

→ kcal/day or cal/hr

what are factors that influence metabolic rate?

→ **age**: growing children have increased BMR, BMR decreases as we age

→ **sex**: males have higher BMR

→ **lean muscle mass vs body fat**: muscle requires more energy to maintain

→ **hormones**: thyroid hormone and epinephrine has a calorigenic effect (increases metabolism)

→ **genetics**

what is food-induced thermogenesis?

when there is a rapid increase in MR due to processing of food by the liver

what happens when you alter calorie intake?

the body attempts to maintain weight within a range

→ increase caloric intake = increases metabolic expenditure and BMR

→ decrease caloric intake = decreases metabolic expenditure and bMR

how does exercise affect weight set points?

exercise increases caloric expenditure

→ **short term**: immediate calorie expenditure

→ **long term**: lowers weight set point and increases metabolic demand with increase muscle mass

what is body mass index (BMI)?

it screens for weight categories that may lead to health problems

→ weight (kg) divided by height squared (m)

→ BMI > 25 is overweight

→ BMI > 30 is obese

→ decreasing BMI can reduce sedentary lifestyles

what are problems with the BMI values?

→ not known at what BMI value increase heart rate

→ confounding factors include sedentary lifestyle/dietary habits

→ patterns of fat deposition (apples vs pears)

what is fed-state/absorptive state?

it is the intake of food and absorption of nutrients from the GI tract

→ nutrients are available and **taken from the nutrient pool** for use by cells

→ excess nutrients will be stored in cells for later use in the liver, muscles, and adipose

→ **anabolism** (building up) occurs to convert nutrients

what is the fasted-state/post-absorptive state?

it is between meals and when the GI tract is empty

→ nutrients are taken from liver, muscles, and adipose stores and **added to the nutrient pool**

→ nutrients are made available to cells

→ **catabolism** (breaking) occurs to convert nutrients)

how would you expect blood glucose concentrations to compare between the fed and fasted states?

the concentration of glucose would be higher in the fed-state compared to the fasted-state

how is glucose used?

it is used for ATP production and synthesis of fats

→ glycogenesis

→ glycogenolysis

→ gluconeogenesis

what is glycogenolysis?

the breaking down of glycogen by all cells, liver (to the bloodstream), and muscles

→ **taking out of glycogen stores and putting back into glucose nutrient pool making it available for cells to use**

what is gluconeogenesis?

the new production of glucose from amino acids, lactate and pyruvate, and glycerol

→ **taking from other pools and putting it into the glucose nutrient pool making it available for cells to use**

how is fatty acids used?

it is used for ATP production, synthesis of lipoproteins (LDL and HDL) and steroids

→ lipogenesis

→ lipolysis

what is lipogenesis?

the production of fats from adipose tissue, free fatty acids, and glucose

→ **taking from free fatty acid pool and excess glucose and put into the fat nutrient store**

what is lipolysis?

the breaking down of fats from adipose tissue and ketone bodies from the liver

→ **taking from fat nutrient stores and put into the free fatty acid pool making it available for cells to use**

how are amino acids used?

it is used for mostly protein synthesis (structural, clotting factors, and enzymes), hormones and neurotransmitters

→ amino acids

→ protein synthesis

what are amino acids?

used by all cells, liver, and muscles

→ **put into the amino acid nutrient pool**

what is protein synthesis?

used by all cells, liver, and muscle

→ **amino acids are taken from the nutrient pool and used for body protein that is eventually put back into the nutrient pool**

nutrients in plasma are available to cells for _____________

cellular respiration and the production of ATP

→ **glucose**: glyogenesis and lipogenesis

→ **amino acids**: protein synthesis

→ **fats**: storage, steroid synthesis, gluconeogenesis

what is cholesterol?

a waxy, hydrophobic, and fat-like substance that's found in all the cells in your body

→ **dietary cholesterol**: animal fats, saturated fats, trans-fatty acids

→ **cholesterol synthesis** by the GI tract and liver

what is low density lipoproteins (LDL)?

a cholesterol that is hydrophobic and needs a carrier to be transported

→ less than 100 mg/dL is optimal

→ **familial hypercholesterolemia**: defective protein component

→ decrease in LDL reuptake by cells = LDL and cholesterol remains in plasma

what is high density lipoproteins (HDL)?

it delivers cholesterol to the liver and to steroid producing cells

→ greater than 40 mg/dL is desirable

what is the LDL:HDL ratio?

the lower the ratio the lower risk of cardiovascular disease (atherosclerosis)

→ men: 3.6 = average risk

→ women: 3.2 = average risk

when the concentration of glucose is low in the plasma, what haappens?

glycogenolysis and gluconeogensis

when the concentration of proteins is low in the plasma, what happen?

amino acids are immediately used for ATP and gluconeogensis

→ **deamination**: NH3 → NH4 → urea

→ amino acids → glucose

when the concentration of fats is low in the plasma, what happens?

→ **lipolysis**: fatty acids are used for ATP, but not in nervous cells

→ **ketone production**: liver takes fatty acids and turns them into ketones in nervous tissue

→ **gluconeogensis**: kicks in during starvation, uses glycerol

what is ketosis and ketoacidosis?

excess ketone production risks the lowering off blood pH

during fed-state, what hormone is released?

beta pancreatic islet cells are triggered with food intake and releases **insulin** to promote glycogenesis, lipogenesis, and protein synthesis

→ **glucose, lipids, and proteins are taken out of the nutrient pool**

→ prevents **hyperglycemia**: when blood glucose is greater than 120 mg/dL

what is the normal blood glucose range?

60-120 mg/dL whole blood

what are the receptors for insulin?

→ **GLUT4** transporters is insulin-**dependent** within adipocytes, cardiac and skeletal muscles

→ **GLUT2** transporters is insulin-**independent** within hepatocytes and beta islet cells

how do GLUT4 transporters work?

insulin binds to receptors causing a signal transduction cascade where GLUT 4 is inserted into the membrane and glucose is taken up by the cell

→ when there is no insulin, GLUT4 is removed (fasted-state)

how do GLUT2 transporters work?

insulin binds to receptors, but has no impact on membrane transporters

→ GLUT2 receptors are always on the membrane

→ hepatocytes convert glucose into glycogen to keep glucose low in the cell and maintain concentration gradient

→ \[glucose\] high outside and low inside

where is GLUT1 and 3 present?

the brain utilizes these transporters in order to always bring in glucose

when is insulin secreted?

→ in a negative feedback mechanism, we begin stimulation of insulin release when **[glucose] is greater than 100 mg/dL**

→ when there is an **increase in plasma amino acids**, beta cells are also stimulated

→ incretins such as **GIP and GLP-1** are involved in a feedforward mechanism that releases insulin in response to nutrients in the duodenum

what is the parasympathetic’s influence on beta pancreatic cells during fed-state?

stimulatory

→ feedforward system activates in response to eating and releases insulin

what is the sympathetic’s influence on beta pancreatic cells during fed-state?

inhibitory

→ stress inhibits the release of insulin and switches from metabolism to gluconeogensis in order to keep nutrient levels high for extra fuel

during fasted-state, what hormone is released?

alpha pancreatic islet cells are triggered between meals to release **glucagon** which promotes glycogenolysis, gluconeogenesis, lipolysis, and protein break down

→ **glucose, lipids, and proteins are taken out of storage and put into the nutrient pool**

→ prevents **hypoglycemia**: when blood glucose levels are below 60 mg/dL

where is glucagon most active?

inn the liver which stores glucose for the rest of the body

→ increases glycogenolysis

→ increases gluconeogenesis

→ increases the production of ketones

→ no known effect on adipocytes

ketones are usually associate with which nutrient state?

fasted-state

→ fatty acids are converted into ketones

→ also associated with uncontrolled diabetes mellitus

when is glucagon released?

there is always a tonic release of glucagon, but when \[glucose\] changes, a negative feedback mechanism occurs

→ increase glucagon release when \[glucose\] is less than 100 mg/dL

→ decrease glucagon release when \[glucose\] is greater than 100 mg/dL

what is the sympathetic’s influence on glucagon during fasted-state?

alpha cells are stimulated to release glucagon

what is the sympathetic’s influence on the adrenal medulla during fasted-state?

stimulates the release of epinephrine which promotes nutrient pools and availability to cells

what is the sympathetic’s influence on the liver during fasted-state?

glycogenolysis and gluconeogenesis

what is the sympathetic’s influence on skeletal muscles during fasted-state?

glycogenolysis

what is the sympathetic’s influence on adipocytes?

lipolysis

during the fasted-state, what is the function of cortisol?

cortisol is released from the adrenal cortex and is permissive for glucagon function

→ allows the liver and adipose to function during this state

→ maintains normal enzyme levels

stress reduces cell sensitivity to insulin, what is the consequence?

→ increase gluconeogensis, protein catabolism, lipolysis

→ decrease muscle and adipose uptake of glucose

during the fasted-state, what is the function of the growth hormone?

growth hormone released from the anterior pituitary will promote protein production and growth

→ with too much of the growth hormone, it has anti-insulin effects

→ increase gluconeogensis, protein catabolism, lipolysis

→ decrease muscle and adipose uptake of glucose

what occurs during fasting?

→ decrease synthesis of organics

→ increase glyogenolysis, lipolysis, and liver gluconeogenesis

what occurs during prolonged fasting?

→ kidney gluconeogenesis

→ increase lipolysis = increased blood ketones, but there is a potential for ketosis and ketoacidosis causing acetone breath and acidic urine

what happens to metabolism when there is an increase in energy demand (exercise)?

→ increase liver glycogenolysis and gluconeogenesis

→ increase adipocyte lipolysis at aerobic rates = most effective

during exercise, reactions are similar to fasting. what occurs?

decrease plasma glucose = decrease insulin = increased glucagon

→ increased sympathetic and epinephrine action

→ increased cortisol and growth hormone action

during exercise, reactions are opposite to fasting. what occurs?

increase glucose uptake and utilization by muscle cells

→ up-regulation of GLUT4 transporters (independent)

→ up-regulation of insulin receptors

why is regular exercise important for people with diabetes?

→ people who are pre-diabetic and begin exercise can stop the progression of type 2 insulin resistance

→ exercise decreases glucose due to the insertion of GLUT4 dependent transporters

→ exercise decreases insulin concentration

what is diabetes mellitus?

“sweet”

→ osmotic diuresis is the solute and water loss causing high specific gravity and concentrated urine

→ glucosuria

→ caused by lack off insulin or functional insulin receptors

what is diabetes insipidus?

“non-sweet”

→ water diuresis is the solvent loss without solute loss causing low specific gravity and dilutes urine

→ caused by lack of vasopressin or functional vasopressin rreceptors

→ central and nephrogenic

what is the blood glucose test?

a person should fast for at least 8 hours before drinking concentrated glucose

→ normal subjects will show increased glucose levels at 30 minutes and then slowly decrease due to insulin

→ per-diabetic subjects will show increased glucose levels after 2 hours due to dysfunctional insulin

what is type I diabetes mellitus?

insulin dependent diabetes which lack the ability to produce insulin because of the autoimmune destruction of beta cells

→ osmotic diuresis

→ diabetic ketoacidosis

when individuals with type I diabetes mellitus, they lack the ability to produce insulin. what are the consequences?

→ low plasma insulin levels

→ high plasma glucose levels: inability to absorb glucose

→ tonic activity of glucagon

→ liver glycogenolysis and gluconeogensis

→ continued lipolysis and protein breakdown

when individuals with type I diabetes mellitus, they suffer from osmotic diuresis. what are the consequences?

→ glucose transport maximum is exceeded

→ the filtered load is greater than the transport maximum

→ glucosuria

→ water follows the solute

one of the pathophysiologies of diabetes mellitus is **dehydration**, what occurs?

→ glucosuria

→ increased Na+ loss and additional water loss

→ polyuria: decreased plasma volume = decreased arterial pressure and blood flow = increase plasma osmolarity

→ polydipsia: hypothalamus telling you that you're thirsty

one of the pathophysiologies of diabetes mellitus is **metabolic acidosis**, what occurs?

→ ketone production

→ circulatory failure requires a switch to anaerobic metabolism which produces additional metabolic acids

one of the pathophysiologies of diabetes mellitus is **tissue loss**, what occurs?

→ continued catabolism and augments hyperglycemia

one of the pathophysiologies of diabetes mellitus is polyphagia, what occurs?

→ no insulin signals to satiety center to increase appetite

what is type II diabetes mellitus?

non-insulin dependent diabetes due to a decreased sensitivity to insulin

→ obesity

→ defective beta pancreatic cells

when individuals with type II diabetes mellitus, they suffer from a decreased sensitivity to insulin. what are the consequences?

→ often there are normal to elevated plasma levels of insulin that ma y progress to reduced insulin

→ high plasma glucose levels

→ inability to absorb glucose

→ continued liver glycogenolysis and gluconeogensis

→ continued lipolysis

how does obesity play a roll in type II diabetes mellitus?

the individual is insulin resistance due to the resistin hormone which is produced in response to excess adipose tissue and involved in inflammation

→ down-regulation of glucose transporters in skeletal muscle and adipose tissue

how do you treat type II diabetes mellitus?

diet and weight reduction along with exercise to increase the number of GLUT4 glucose transporters in skeletal muscle cells

what is hypoglycemia?

lose plasma glucose concentration usually seen in a fasted-state

what are potential causes of hypoglycemia?

→ excess insulin due to B cell tumors, excess insulin injection, and increased insulin secretion

→ poor fasted state regulation due to liver disease, inactive alpha cells, decreased glucagon secretion, and decreased glycogenolysis, gluconeogensis, and cortisol

what are symptoms of hypoglycemia?

→ sympathetic nervous system responds with increased heart rate, sweating, anxiety and nervousness

→ lack of glucose to the brain causing headache, confusion, dizziness, lack of coordination, convulsions, unconsciousness, and coma

what is the temperature balance equation?

temperature balance = heat production + gain - loss

→ 35.5-37.7 decrees C

→ 96-99 degrees F

what is radiation?

electromagnetic waves

→ gain or loss

what is conduction?

physical contact

→ gain or loss

what is convenction?

moving air or water

→ usually loss, some gain

what is evaporation?

liquid to gaseous phase

→ loss only

what is core temperature?

beneath the skin and subcutaneous layer

what is shell temperature?

skin and subcutaneous layer

→ generally 1-6 degrees C lower than core temperature

what is the thermoneutral zone?

21\.8-30 degrees C; 82-86 degrees F

→ ambient temperature in which heat gain = loss

→ maintain appropriate body temperature through regulation of blood flow

→ no changes in metabolic heat production or evaporative heat loss

what do peripheral thermoreceptors do?

in skin to provide feedforward action

what do central thermoreceptors do?

in hypothalamus that regulate with negative feedback

what is voluntary regulation?

within the motor cortex, the motor system acts voluntarily for heat gan and loss

→ clothing, voluntary movement, body position, eating and food thermogenesis

how does the hypothalamus control the sympathetic system of thermoregulation with cholinergic neurons?

**cholinergic neurons** are used to initiate heat loss by **vasodilating** the cutaneous blood vessels involuntarily