Unit 10 - Metabolism & Energy Balance

Question 1

Once nutrients are ingested, digested and absorbed by the digestive system, they can…

Answer 1

be used for various metabolic processes.

Question 2

Metabolism

Answer 2

Is the sum of all chemical reactions in the body

Question 3

Metabolism

Includes:

Answer 3

1. Anabolic pathways

2. Catabolic pathways

Question 4

Anabolic pathways

Answer 4

that build larger molecules from smaller ones.

Question 5

Catabolic pathways

Answer 5

that breakdown larger molecules into smaller ones.

Question 6

There are two different metabolic states:

Answer 6

1. Fed or absorptive state

2. Fasted or post-absorptive state

Question 7

Fed or absorptive state:

Answer 7

overall ANABOLIC state following a meal when plasma levels of absorbed nutrients are high and are used to build high energy compounds (like ATP and phosphocreatine) or are converted into storage forms for later use.

(period of time following a meal, when the products of digestion are being absorbed, used, & stored)

Question 8

Fasted or post-absorptive state:

Answer 8

overall CATABOLIC state occurring between meals when plasma levels of absorbed nutrients are low and the body breaks down stored nutrients (i.e. taps into its stored reserves) to obtain the molecules needed

(once nutrients from a recent meal are no longer in the bloodstream & avail. for use by the tissues, the body enters this state)

Question 9

The fate of absorbed nutrients is one of the following:

Answer 9

1. Energy production.
2. Synthesis
3. Storage.

Question 10

Energy production.

Answer 10

Biomolecules are broken down, releasing energy that is stored in the bonds of high energy molecules like ATP, phosphocreatine

Question 11

Synthesis

Answer 11

of biomolecules required for growth and maintenance of tissues (for example, synthesis of cell
membranes and membrane proteins, synthesis of actin and myosin in muscle cells, etc.)

Question 12

Storage.

Answer 12

When plasma levels of an ingested nutrient exceeds the levels required for energy production and synthesis, the remainder is stored as either glycogen or fat (mostly the latter since glycogen stores in the liver and skeletal muscle tissue are limited).

Question 13

Whether a nutrient is used for energy production, synthesis of biomolecules or is stored depends on…

Answer 13

whether the body is in the fed or fasted state.

Question 14

Carbohydrate Metabolism

Fed (Absorptive) State Metabolism:

Answer 14

After absorption, almost all absorbed monosaccharides that are not glucose (i.e. fructose and galactose) are converted to glucose in the liver. As a result, 95% of all monosaccharides circulating in the blood plasma are glucose.

Circulating glucose enters tissue cells (e.g. skeletal muscle cells) by facilitated diffusion using GLUT (glucose transport) carrier proteins.

Once inside of cells, glucose is immediately phosphorylated into GLUCOSE-6-PHOSPHATE via the action of the enzyme GLUCOKINASE (in liver cells) or HEXOKINASE (all other cells). This helps to trap glucose inside of the cell and maintain concentration gradients of glucose that favour movement of glucose into the cells.

Question 15

Carbohydrate Metabolism

Fed (Absorptive) State Metabolism:

The type of GLUT used is specific to the tissue:

Answer 15

a. GLUT2 in liver (similar to kidney).
b. GLUT3 in neurons.
c. GLUT4 in skeletal and cardiac muscle cells, and adipose cells. Insulin increases the number of GLUT4 proteins in cell membranes and therefore increases glucose transport into these cells.

Question 16

Carbohydrate Metabolism

Fed (Absorptive) State Metabolism:

During the fed state, glucose-6-phosphate is:

Answer 16

a. Converted into ATP via glycolysis, the citric acid cycle, and the electron transport chain (aerobic pathways for ATP synthesis)
b. Stored as glycogen.
c. Stored as fat.
d. Used for lipoprotein synthesis.

Question 17

Carbohydrate Metabolism
1. Fed (Absorptive) State Metabolism:

During the fed state, glucose-6-phosphate is:

a. Converted into ATP via glycolysis, the citric acid cycle, and the electron transport chain (aerobic pathways for ATP synthesis)

Answer 17

i. GLYCOLYSIS = conversion of glucose-6-phostphate to 2 pyruvate, in the cytosol of the cell. Produces net 2 ATP.
ii. In mitochondria, pyruvate is converted to Acetyl Coenzyme A.
iii. Acetyl CoA enters the CITRIC ACID CYCLE (aka Krebs cycle), and under the effects of multiple enzymes is converted into a cascade of products, the end results of which produces net 2 ATP, along with carbon dioxide and hydrogen ions and high energy electrons.
iv. The flow of H+ down a gradient is involved in the oxidative phosphorylation of ADP to ATP in the ELECTRON TRANSPORT CHAIN (ETC) process. The ETC produces net 28 ATP.
v. Overall net ~32 ATP are produced by this process.

Question 18

Carbohydrate Metabolism
1. Fed (Absorptive) State Metabolism:

During the fed state, glucose-6-phosphate is:

b. Stored as glycogen.

Answer 18

• Glycogenesis = formation of glycogen (a polymer
  of glucose) from glucose.
• Glycogen stores are limited – they store enough glycogen to satisfy the body’s energy needs for 12-24 hours.
• Steps:
  i. Glucose-6-phosphate is converted to
  glucose-1-phosphate.
  ii. glucose 1-phosphate is converted to uridine- diphosphate glucose
  iii. Uridine diphosphate glucose is converted to glycogen.

Question 19

Carbohydrate Metabolism
1. Fed (Absorptive) State Metabolism:

During the fed state, glucose-6-phosphate is:

c. Stored as fat.

Answer 19

Any excess glucose is converted to triglycerides and stored in adipose tissue (LIPOGENESIS). Involves:

i. Conversion of glucose and/or glycolysis intermediates into glycerol.
ii. Conversion of acetyl CoA molecules (produced as a result of glucose catabolism) into fatty acids via the action of FATTY ACID SYNTHETASE.
iii. Inside of the smooth ER, the glycerol from (a) and the fatty acids from (b) are combined to form triglycerides.

Question 20

Carbohydrate Metabolism
1. Fed (Absorptive) State Metabolism:

During the fed state, glucose-6-phosphate is:

d. Used for lipoprotein synthesis.

Answer 20

Acetyl CoA from glucose metabolism can be used for production of lipoproteins (e.g. LDL and HDL). Lipoproteins are responsible for carrying insoluble fat and cholesterol in the plasma.

Question 21

LDL =

Answer 21

low density lipoproteins

Question 22

HDL =

Answer 22

high density lipoproteins

Question 23

Carbohydrate Metabolism

2. Fasted (Post-Absorptive) State Metabolism:

Answer 23

During the fasted state, stored carbohydrates are converted back into glucose to be used for ATP production (meets energy demands between meals).

a. Glycogenolysis: Glycogen is converted to glucose-6- phosphate and glucose. Involves:
i. Conversion of glycogen into Glucose-1-phosphate, through the action of the enzyme phosphorylase.
ii. Conversion of Glucose-1-phosphate to glucose-6- phosphate.
iii. Glucose-6-phosphate can then enter glycolysis in the cell or be converted to glucose (via the enzyme
glucose phosphatase) and released into the blood).

b. Gluconeogenesis: production of glucose from substrates other than glycogen, including amino acids and triglycerides.

Question 24

Glycogenolysis:

Answer 24

Glycogen is converted to glucose-6- phosphate and glucose.

Question 25

Gluconeogenesis:

Answer 25

production of glucose from substrates other than glycogen, including amino acids and triglycerides.

Question 26

Glycogen can be converted directly to glucose 6-phosphate by the addition of phosphate. Glycogen that is broken down first to glucose & then phosphorylated...

Answer 26

"costs" the cell an extra ATP

Question 27

Lipid Metabolism | 1. Fed (Absorptive) State Metabolism:

Answer 27

Recall from Unit 9 – most lipids are packaged into lipoproteins/lipid complexes called CHYLOMICRONS, which exit enterocytes via exocytosis and are absorbed by the lymph lacteals. Some short chain fatty acids (less than 12 carbons long) are absorbed into the blood by simple diffusion.

Question 28

Chylomicrons contain

Answer 28

triglycerides (87%), phospholipids (9%), cholesterol (3%) and apolipoprotein (1%).

Question 29

Lipid Metabolism 1. Fed (Absorptive) State Metabolism: During the fed state:

Answer 29

a. The enzyme LIPOPROTEIN LIPASE (found on the capillary endothelium in adipose, liver and muscle tissues) breaks down the triglycerides of the chylomicron into monoglycerides and fatty acids that can diffuse into tissue cells. b. Adipose and liver cells convert monoglycerides and fatty acids into triglycerides (LIPOGENESIS), and store them until needed. High insulin levels during the fed state suppress fatty acid oxidation in other tissues (e.g. skeletal muscle) and increase oxidation of glucose. c. The leftover parts of the chylomicron (namely the apolipoprotein and cholesterol) are taken to the liver. d. LDL-C is transported to cells that will use the cholesterol for synthesis (e.g. building cell membranes, steroid hormone synthesis, etc). e. Excess glucose and protein are converted to triglycerides - LIPOGENESIS – glucose or amino acids are converted to pyruvate and then to Acetyl CoA. Acetyl CoA is used to produce fatty acids, which can then be incorporated into triglycerides in adipose tissue cells (or liver cells) for storage.

Question 30

Cholesterol can be used...

Answer 30

to form bile acids/salts, or can be repackaged into lipoproteins formed in the liver. (the body can make cholesterol from acetyl CoA through a series of rxns)

Question 31

Cholesterol can be used to form bile acids/salts, or can be repackaged into lipoproteins formed in the liver. The most important are the

Answer 31

LOW DENSITY LIPOPROTEINS (including LDL cholesterol, LDL-C) and HIGH DENSITY LIPOPROTEINS (like HDL cholesterol, HDL-C).

Question 32

Lipoproteins that have a high concentration of protein are

Answer 32

high density

Question 33

LDL cholesterol (LDL-C)

Answer 33

is known to cause atherosclerosis (build up of lipid plaques inside blood vessels), leading to arteriosclerosis (stiffening of blood vessels) that can cause high blood pressure, cardiovascular disease, stroke, etc. ("lethal cholesterol")

Question 34

HDL-C

Answer 34

is “healthy” cholesterol as it carries cholesterol back to the liver where it can be eliminated in bile.

Question 35

Lipid Metabolism 2. Fasted (Post-Absorptive) State Metabolism:

Answer 35

Most of the body’s energy reserves are stored as lipids. During the fasted state (in between meals), stored triglycerides are broken down and the components used in various pathways to meet energy demands between meals. Involves: a. Lipolysis

Question 36

Lipid Metabolism 2. Fasted (Post-Absorptive) State Metabolism: Involves:

Answer 36

a. Lipolysis – breakdown of triglycerides into fatty acids and glycerol for ATP production. i. Triglycerides in adipose tissue are hydrolyzed into glycerol and fatty acids by the intracellular enzyme HORMONE SENSITIVE-LIPASE (HSL). ii. Glycerol is transported to the liver where it undergoes GLUCONEOGENESIS to become glucose, which can then be used as a substrate for glycolysis and ATP production in various tissues (skeletal muscle, brain, etc). iii. Fatty acids are transported in the blood bound to albumins: • At target tissues they enter the mitochondria and undergo BETA-OXIDATION which removes 2-carbon acyl units from the fatty acid. These acyl units are then converted into acetyl CoA which is used in the citric acid cycle to produce ATP. • In the liver, fatty acids undergo beta-oxidation to form ketone bodies. Ketones can then be used as an energy source to produce ATP (particularly by the brain during starvation).

Question 37

Protein Metabolism 1. Fed (Absorptive) State Metabolism:

Answer 37

- Recall from Unit 9 – most proteins are absorbed as amino acids. - After absorption into the blood, they are first delivered to the liver, which uses them to synthesize plasma proteins like albumins and lipoprotein (such as LDL-C and HDL-C) that will transport lipids in the blood. Amino acids are then circulated to the rest of the tissues in the body and used by cells for protein synthesis (via transcription and translation of DNA and mRNA).

Question 37

Protein Metabolism 1. Fed (Absorptive) State Metabolism:

Answer 37

- Recall from Unit 9 – most proteins are absorbed as amino acids. - After absorption into the blood, they are first delivered to the liver, which uses them to synthesize plasma proteins like albumins and lipoprotein (such as LDL-C and HDL-C) that will transport lipids in the blood. Amino acids are then circulated to the rest of the tissues in the body and used by cells for protein synthesis (via transcription and translation of DNA and mRNA).

Question 38

Protein Metabolism 1. Fed (Absorptive) State Metabolism: Unlike for carbohydrates and lipids, there is no...

Answer 38

storage form of amino acids in the body. Excess amino acids in the blood can be converted to pyruvate (through the process of deamination – removal of an amino group – NH2). Pyruvate is then converted to Acetyl CoA in the mitochondria, and can be used for: - Lipogenesis – by converting Acetyl CoA into fatty acids. - Aerobic production of ATP (enters citric acid cycle).

Question 39

If glucose intake is LOW...

Answer 39

AA's can be used for energy (in fasted-state)

Question 40

If more protein is ingested than is needed for syn. & energy expenditures...

Answer 40

excess AA's are converted to fat

Question 41

When AA intake exceeds the body's need for protein syn...

Answer 41

excess AA's are burned for energy or stored as fat

Question 42

Protein Metabolism 2. Fasted (Post-Absorptive) State Metabolism:

Answer 42

- Free amino acids in the blood are be used to make ATP. If the fasted state lasts a particularly long time (e.g. starvation), then the body will actively breakdown muscle tissue to supply amino acids for protein synthesis and for ATP production. - Like the fed state, amino acids undergo deamination – removal of an amino group (NH2), which forms ammonia (NH3) and and an organic acid. - Organic acid can enter the citric acid cycle to produce ATP. - NH3 is toxic, and so is converted to ammonium (also toxic) and then into urea in the liver. Urea can then be filtered by the kidneys and excreted in the urine (it also contributes to vertical osmotic gradient in the kidney – see unit 8). Amino acids can also be used to produce glucose via gluconeogenesis (the reverse of glycolysis). a. Amino acids are deaminated and their organic acids can either directly undergo gluconeogenesis or they can be converted to pyruvate which will undergo gluconeogenesis. b. Product of gluconeogenesis is glucose-6-phosphate. c. Glucose -6-phosphate is converted to glucose (by phosphatase in the liver).

Question 43

Extrinsic Control of Metabolism

Answer 43

As we have seen in the previous sections, metabolic processes in both the fed and fasted states are mediated by enzymes. Often the forward and reverse reactions are mediated by separate enzymes, which allows for “push-pull” control of a metabolic process by upregulating the activity of one enzyme and downregulating the activity of the other. Modulation of metabolic enzyme activity occurs as a result of hormonal stimuli, however neural stimuli can also be involved.

Question 44

Extrinsic Control of Metabolism Modulation of metabolic enzyme activity occurs as a result of hormonal stimuli, however neural stimuli can also be involved.

Answer 44

- For example: in carbohydrate metabolism, insulin promotes the activity of enzymes that cause glycogen formation (glycogenesis) during the fed state and inhibits enzymes that promote glycogen break down (glycogenolysis). - In contrast, glucagon promotes the activity of the enzymes that cause glycogenolysis during the fasted state, and inhibits the activity of the enzymes that cause glycogenesis.

Question 45

Extrinsic Control of Metabolism An important step in making the transition between fed state and fasted state metabolism is...

Answer 45

the behavioural regulation of food intake and satiety.

Question 46

Food intake is thought to be controlled by ____ ____ and ____ ____ in the hypothalamus.

Answer 46

feeding centre satiety centres

Question 47

Food intake is thought to be controlled by feeding centres and satiety centres in the hypothalamus. Two theories exist as to how these centres are controlled:

Answer 47

1. Glucostatic theory | 2. Lipostatic theory

Question 48

Glucostatic theory

Answer 48

suggests that food intake is controlled by blood glucose levels. When blood glucose levels are low the satiety centre is suppressed and the activity of the tonically active feeding centre dominates, causing food intake.

Question 49

Lipostatic theory

Answer 49

suggests that food intake is controlled by signals from the body’s adipose tissues (fat stores), and that when fat stores are increased, the activity of the feeding centres is inhibited and food intake decreases.

Question 50

Extrinsic Control of Metabolism Some peptide hormones and neurotransmitters released by the gut and hypothalamus are known to stimulate the feeding centres of the brain and increase food intake. These include:

Answer 50

1. neuropeptide Y (NPY) | 2. ghrelin

Question 51

Neuropeptide Y (NPY)

Answer 51

is a neurotransmitter released in the hypothalamus, which is a potent stimulator of the hypothalamic feeding centres.

Question 52

Ghrelin

Answer 52

(which is released mainly by enteroendocrine cells in the stomach) stimulates release of NPY and so acts to stimulate feeding and hunger.

Question 53

Several hormones act to either stimulate the satiety centre or inhibit the action of feeding centre (particularly through inhibition of neuropeptide Y, NPY) thereby decreasing food intake..These include:

Answer 53

1. Cholecystokinin (CCK) 2. Glucose-like peptide-1 (GLP-1) 3. Leptin 4. Corticotropin-releasing hormone 5. Peptide YY

Question 54

Cholecystokinin (CCK)

Answer 54

released by the small intestine, and stimulates the satiety centre.

Question 55

Glucose-like peptide-1 (GLP-1)

Answer 55

also released by the small intestine stimulates the satiety | centre.

Question 56

Leptin

Answer 56

released from adipose tissue cells in response to an increase in fat storage and acts to inhibit the actions of NPY.

Question 57

Corticotropin-releasing hormone

Answer 57

released by the hypothalamus inhibits NPY and decreases food intake, which may explain why some people lose their appetite in times of chronic stress.

Question 58

Peptide YY

Answer 58

released from small and large intestine after intake of food. Inhibits NPY and therefore decreases food intake.

Question 59

Disruptions in the functions of these hormones (hormone resistance, hyposecretion of hormones that stimulate satiety centre/inhibit feeding centre OR hypersecretion of hormones that inhibit satiety centre/stimulate feeding centre can play important roles in...

Answer 59

the pathophysiology of obesity

Question 60

Extrinsic Control of Metabolism The two most important hormones controlling metabolism and the transition between the fed and fasted states are...

Answer 60

insulin and glucagon produced by the endocrine pancreas. While both of these hormones are often circulating in the blood simultaneously, the ratio of insulin to glucagon in the blood plasma at any given time, determines the dominant metabolic state at that moment. Insulin levels are higher during the fed state, while glucagon levels are higher during the fasted state. As such, plasma insulin levels increase right after a meal, while plasma glucagon levels decrease.

Question 61

Insulin levels are higher during the ____ state, while glucagon levels are higher during the ____ state.

Answer 61

FED FASTED

Question 62

As such, plasma insulin levels _____ right after a meal, while plasma glucagon levels ______.

Answer 62

INCREASE DECREASE

Question 63

Extrinsic Control of Metabolism 1. Insulin (dominates in fed state)

Answer 63

peptide hormone produced by BETA cells in the Islets of | Langerhans in the pancreas.

Question 64

Extrinsic Control of Metabolism 1. Insulin (dominates in fed state) Secretion of insulin from beta cells is STIMULATED BY:

Answer 64

a. HIGH PLASMA GLUCOSE LEVELS: >100 mg/dL b. HIGH CONCENTRATIONS OF AMINO ACIDS in the plasma. c. GI Tract hormones – including GLP-1 and GIP. - GLP-1 (glucose-like peptide-1) and GIP (gastric inhibitory peptide) are released in response to the presence of carbohydrates in the lumen of the small intestine. d. PARASYMPATHETIC ACTIVITY – beta cells are innervated by the PSNS, and so PSNS neurons can amplify insulin secretion. - after eating a meal: distension of the GI tract wall activates stretch receptors that send sensory input to the brain triggering an increase in PSNS activity.

Question 65

Extrinsic Control of Metabolism 1. Insulin (dominates in fed state) Secretion of insulin from beta cells is INHIBITED BY:

Answer 65

a. SYMPATHETIC ACTIVITY and CATECHOLAMINES FROM ADRENAL GLAND (epinephrine and norepinephrine).

Question 66

Extrinsic Control of Metabolism 1. Insulin (dominates in fed state) Target tissues:

Answer 66

a. Primarily liver, muscle and adipose tissue. b. Some tissues do not rely on insulin to obtain glucose, including the brain, kidneys and intestines. They possess an insulin-independent GLUT transporter, that will allow for adequate glucose transport even when plasma insulin levels are low.

Question 67

Extrinsic Control of Metabolism 1. Insulin (dominates in fed state) Mechanism of action: second messenger system

Answer 67

a. Insulin receptors are tyrosine kinase receptors in the membranes of target cells. b. Binding of insulin to the receptor activates phosphorylation of insulin receptor substrates (IRS) c. IRSs activate second messenger pathways that alter protein synthesis and the activity of existing proteins in the cell. d. End result is a change in membrane transport of glucose (increases transport into the cell) as well as a change in the metabolic activity of the cell (increases glucose use). - e.g. in skeletal muscle cells second messenger stimulates vesicles to insert GLUT4 transporters into the cell membrane which increases the glucose entry into the cells.

Question 68

Extrinsic Control of Metabolism 1. Insulin (dominates in fed state) Effects of Insulin:

Answer 68

(overall ANABOLIC – stimulates building of macromolecules) a. Increases glucose transport into target cells (especially skeletal and cardiac muscle and adipose tissue cells). E.g. 1: Skeletal muscle cells: During the fasted resting state, the absence of insulin prevents skeletal muscle cells from transporting glucose, since there are no GLUT4 transporters in the membrane. As such, RESTING FASTED MUSCLES RELY PRIMARILY ON FATTY ACID OXIDATION FOR ENERGY PRODUCTION. During the fed state insulin signals the cells and the cells respond by inserting GLUT4 transporters into their membranes (via exocytosis of vesicles that contain GLUT4 transporters in their membranes). With a transporter in place during the fed state, the cells uptake glucose from the plasma (decreasing plasma concentrations of glucose). Movement of glucose into adipose tissue is regulated in a similar manner. E.g. 2: Liver cells: These cells always have a GLUT transporter in their membranes, specifically GLUT2. This is due to the fact that glucose needs to move across the membrane of liver cells during both the fed and fasted states. i. In the fasted state, liver cells produce glucose by breaking down glycogen (glycogenolysis) or by converting amino acids or triglycerides into glucose (gluconeogenesis) . This production of glucose in the liver cell increases intracellular glucose concentrations, and glucose will move out of the cell by facilitated diffusion through the GLUT2 transporter. (a carrier protein) ii. In the fed state, the glucose concentration is higher in the blood than in the cell, so transport though the GLUT2 transporter reverses, and liver cells uptake glucose from the blood. They can then use this glucose to produce ATP (glycolysis, etc) or store it as glycogen (glycogenesis). b. Increases glucose use and storage by target cells. - Activates enzymes for glycolysis and glycogenesis. - Inhibits the enzymes for gluconeogenesis and lipolysis. c. Activates enzymes involved in protein synthesis (and inhibits enzymes involved in protein catabolism). d. Promotes synthesis of fats (lipogenesis) from all substrates (including excess glucose and amino acids) and inhibits beta- oxidation of fatty acids (prevents gluconeogenesis from fatty acids).

Question 69

Extrinsic Control of Metabolism 1. Insulin (dominates in fed state) Overall effect:

Answer 69

in response to high plasma glucose levels, insulin causes a decrease in plasma glucose levels (homeostatic control of blood glucose).

Question 70

Extrinsic Control of Metabolism 2. Glucagon (dominates in fasted state)

Answer 70

produced by ALPHA cells in the Islet of Langerhans in the pancreas.

Question 71

Extrinsic Control of Metabolism 2. Glucagon (dominates in fasted state) Glucagon secretion from the pancreas is STIMULATED BY:

Answer 71

a. Hypoglycemia = low plasma glucose levels (<85-70mg/dL) b. High concentrations of amino acids in the blood. c. Sympathetic (or adrenal epinephrine) stimulation of the pancreatic alpha cells.

Question 72

Extrinsic Control of Metabolism 2. Glucagon (dominates in fasted state) Glucagon secretion from the pancreas is INHIBITED BY:

Answer 72

a. high plasma glucose levels

Question 73

Extrinsic Control of Metabolism 2. Glucagon (dominates in fasted state) Target Tissues

Answer 73

primarily the liver.

Question 74

Extrinsic Control of Metabolism 2. Glucagon (dominates in fasted state) Effects

Answer 74

a. Stimulates glycogenolysis (break down of glycogen) b. Stimulates gluconeogenesis (formation of glucose from non-carbohydrate substrates like fatty acids or amino acids). c. Stimulates lipolysis (breakdown of of fats). Products of lipolysis in the fasted stated are converted to ketones in the liver (ketogenesis). Overall effect: in response to low plasma glucose levels, glucagon causes an increase in plasma glucose levels (homeostatic control of blood glucose).

Question 75

Extrinsic Control of Metabolism 3. Cortisol (stress hormone)

Answer 75

- Resting/normal levels of cortisol are permissive for gluconeogenesis and lipolysis during the fasted state. - High levels of cortisol: a. increase break down (catabolism) of protein b. increase gluconeogenesis c. Increase lipolysis (break down of triglycerides). d. decrease glucose uptake by muscle cells and adipose-tissue cells

Question 76

Extrinsic Control of Metabolism 4. Growth Hormone

Answer 76

- Stimulates protein synthesis - Effects on carbohydrate and fat metabolism are minimal, but are opposite to the effects of insulin (anti- insulin effects) similar to those exhibited by cortisol: a. Increases gluconeogenesis.. b. Increases lipolysis. c. Inhibits glucose uptake

Question 77

Extrinsic Control of Metabolism 5. Epinephrine and Sympathetic Nerves to Liver and Adipose Tissue

Answer 77

In addition to the effects on the pancreas (stimulating glucagon secretion and inhibiting insulin release), sympathetic stimulation and epinephrine can affect nutrient metabolism directly by acting on liver cells and adipose tissue cells. Overall, the function of this “fight-or-flight” stimulation is to mobilize nutrients to provide substrates (glucose) for ATP synthesis. These would all be important for example during exercise. a. Promotes lipolysis in adipose tissue by stimulating activity of hormone sensitive-lipase (HSL) b. Promotes glycogenolysis and and gluconeogenesis in the in liver c. Sympathetic activity also stimulates glycogenolysis in skeletal muscle cells

Question 78

Diabetes mellitus

Answer 78

is a group of conditions characterized by chronic HYPERGLYCEMIA (abnormally high blood glucose concentrations) that results from reduced insulin secretion (Type 1 diabetes) or reduced responsiveness of target cells (Type 2 diabetes), or both.

Question 79

Chronic hyperglycemia

Answer 79

can cause damage to the eyes (diabetic retinopathy), kidneys, blood vessels (leading to cardiovascular disease), and nervous system (diabetic neuropathy).

Question 80

Metabolic Imbalance: Diabetes mellitus Two main types:

Answer 80

1. Type 1 diabetes mellitus | 2. Type 2 diabetes mellitus

Question 81

Type 1 diabetes mellitus

Answer 81

= insulin deficiency due to autoimmune destruction of beta cells In the absence of insulin, blood glucose levels are high due to a) reduced uptake by cells and b) loss of the inhibitory effects of insulin on glycogenolysis and gluconeogenesis. Treatment = insulin injections.

Question 82

Type 1 diabetes mellitus Without the ability to uptake glucose (and amino acids) insulin dependent cells enter fasted state metabolism and produce the responses characteristic of Type 1 diabetes including:

Answer 82

a. Break down of muscle tissue to provide substrates for ATP and protein synthesis. Leads to loss of muscle tissue. b. Lipolysis of adipose to release substrates for ATP production (fatty acids). Leads to loss of fat tissue. Some fatty acids undergo beta-oxidation and gluconeogenesis in the liver, which also produces ketones. c. If left untreated, ketone production can lead to METABOLIC ACIDOSIS (i.e. ketoacidosis). - see Unit 8. - Signs of metabolic acidosis include – increased ventilation, decreased pH of urine (as H+ ions are secreted into filtrate), hyperkalemia. d. Polyuria and glucosuria: excessive glucose in the blood is filtered by the kidney but exceeds the renal threshold and transport maximum for reabsorption in the nephron (see unit 7). The excess glucose in the filtrate prevents reabsorption of water and leads to production of a high volume of dilute urine, that contains glucose (glucosuria). e. Dehydration: due to higher water loss in urine. f. Polydipsia: excessive thirst (due to dehydration). g. Polyphagia: lack of glucose uptake and utilization by tissues is interpreted by the brain as starvation, which results in excessive hunger and food consumption.

Question 83

Polyuria and glucosuria:

Answer 83

excessive glucose in the blood is filtered by the kidney but exceeds the renal threshold and transport maximum for reabsorption in the nephron (see unit 7). The excess glucose in the filtrate prevents reabsorption of water and leads to production of a high volume of dilute urine, that contains glucose (glucosuria).

Question 84

Dehydration:

Answer 84

due to higher water loss in urine.

Question 85

Polydipsia:

Answer 85

excessive thirst (due to dehydration).

Question 86

Polyphagia:

Answer 86

lack of glucose uptake and utilization by tissues is interpreted by the brain as starvation, which results in excessive hunger and food consumption.

Question 87

Metabolic Imbalance: Diabetes mellitus 2. Type 2 diabetes mellitus

Answer 87

= insulin resistant diabetes (insulin receptors do not respond to insulin). Type 2 diabetes may be associated with lower or higher insulin production, however... Because insulin is still present, tissues can carry out a small amount of glucose metabolism. This is usually enough to prevent many of the hallmark features that are associated with Type 1 diabetes. For example, because a small level of glucose uptake is possible, the formation of ketone bodies in the liver is not needed. As a result, metabolic acidosis is a rare occurrence in people with type 2 diabetes. However, hyperglycemia can still lead to polyuria, glucosuria, dehydration, increased thirst, etc. But the tissue loss and ketone production associated with Type 1 diabetes are often reduced except in severe cases.

Question 88

Energy Balance & Metabolic Rate

Answer 88

The nutrients we take into our body are used to produce energy. Energy is conserved, so while it can be converted from one form to another, the amount of energy input into a system (like our bodies) must be equal to the energy output in order to maintain balance.

Question 89

Total body energy =

Answer 89

energy stored + energy intake – energy loss.

Question 90

Total body energy = energy stored + energy intake – energy loss. Where:

Answer 90

energy intake is derived from the ingestion, digestion and absorption of nutrients (see Unit 9).

Question 91

Energy output is in the form of work and heat. The three types of work done in the body are:

Answer 91

Transport work - active transport processes across membranes. Chemical work – metabolic reactions that synthesize and store energy molecules, like ATP, glycogen, fat). Mechanical work – all types of muscle contractions, cell movements, etc.

Question 92

Energy use in the body is measured using

Answer 92

estimates of the energy content of the food we ingest and the energy we expend as both heat and work.

Question 93

Energy content in food is measured in

Answer 93

kilocalories (the amount of heat released from burning of the food that it would take to raise the temperature of 1 L of water by 1○C). 1 kilocalorie = 1 Calorie

Question 94

The energy content of proteins and carbohydrates is estimated to be

Answer 94

~4 kcal/g

Question 95

The energy content of fat is

Answer 95

~9 kcal/g

Question 96

Based on these estimates, we can calculate the caloric content of any food just by knowing how many grams of fat, carbohydrates and proteins there are in the food. For example, a package of high protein oatmeal contains 2g of fat, 26 g of carbohydrates, 6 g of protein. So:

Answer 96

Kilocalories from fat = 2 g x 9 kcal/g = 18 kcal Kilocalories from carbs = 22* g x. 4 kcal/g = 104 kcal Kilocalories from proteins = 6 g x 4 kcal/g = 24 kcal TOTAL kilocalories = 18 + 104 + 24 = 130 kcal

Question 97

Note: When calculating caloric content from carbohydrates , insoluble fibre is...

Answer 97

NOT included in the calculation as the body is unable to digest these fibers and so receives no energy from them. In our example, the oatmeal contains 4g of insoluble fibre, so this is subtracted from the total amount of carbs.

Question 98

The metabolic rate

Answer 98

is a measure of the amount of energy that the body uses to do work (energy expenditure).

Question 99

Basal metabolic rate (BMR)

Answer 99

is the amount of energy the body used (energy expenditure) at rest.

Question 100

A person’s metabolic rate can be estimated by measuring:

Answer 100

a person’s oxygen consumption (~ 4.5-5 kcal of food energy is used per litre of O2 consumed)

Question 101

Metabolic rate (kcal/day) =

Answer 101

O2 consumption/day (L) × kcal/L O2

Question 102

For example, if a person at rest has an oxygen consumption of 0.5 L/min, then they consume 0.5L/min x 1440 min/day = 2160 L/day. (minutes per day = 60 min/hr x 24 hours/day). 2160 L/day x 4.5 kcal/L = 3240 kcal/day If this person’s energy consumption from food intake during the day exceeded 3240 kcal, then

Answer 102

there is an energy imbalance that will cause storage of nutrients and weight gain. If less than 3240 kcal was consumed, then there is an energy imbalance that will cause removal of nutrients from storage and weight loss.

Question 103

For example, if a person at rest has an oxygen consumption of 0.5 L/min, then they consume 0.5L/min x 1440 min/day = 2160 L/day. (minutes per day = 60 min/hr x 24 hours/day). 2160 L/day x 4.5 kcal/L = 3240 kcal/day However, the body is also is capable of changing energy expenditures in response to changes in food intake. For example, a decrease in intake can result in

Answer 103

decreased expenditure. This is why diet alone is not enough to cause weight loss, but must be combined with exercise to maintain or augment expenditure.

Question 104

Factors Affecting Basal Metabolic Rate

Answer 104

1. Age 2. Sex 3. Lean muscle mass 4. Activity level 5. Diet 6. Hormones 7. Genetics

Question 105

1. Age

Answer 105

BMR decreases with age.

Question 106

2. Sex

Answer 106

Males usually have higher BMR than females (related to higher lean muscle mass).

Question 107

3. Lean muscle mass

Answer 107

as muscle mass increases, BMR increases, as muscle consumes more oxygen at rest than adipose tissue (even at rest).

Question 108

4. Activity level

Answer 108

increasing activity produces departures from the BMR. Metabolic rate increases with increasing activity levels.

Question 109

5. Diet

Answer 109

metabolic rate increases after eating due to diet-induced thermogenesis. Eating protein produces the largest increase.

Question 110

6. Hormones

Answer 110

a. THYROID HORMONE (T3, T4) – most important determinant of BMR regardless of age, sex, and body size. Increases O2 consumption and heat production in most tissues. Ability to increase BMR = calorigenic effect. b. CATECHOLAMINES (Epinephrine and Norepineprhine) - increase metabolic rate

Question 111

Regulation of Body Temperature

Answer 111

Humans are homeothermic and body temperature is regulated to maintain it within a narrow range of values (35.5-37.7 C) Body temperature is regulated by balancing the amount of heat production and/or gain with the amount of heat loss.

Question 112

1. Mechanisms of HEAT PRODUCTION/GAIN in the body:

Answer 112

a. INTERNAL HEAT PRODUCTION from METABOLIC PROCESSES or MUSCLE CONTRACTIONS i. SHIVERING THERMOGENESIS ii. NON-SHIVERING THERMOGENESIS iii. DIET-INDUCED THERMOGENESIS b. RADIANT HEAT GAIN c. CONDUCTIVE HEAT GAIN

Question 113

Shivering thermogenesis

Answer 113

involuntary skeletal muscle contractions producing heat .

Question 114

Non-shivering thermogenesis

Answer 114

increased heat production by Brown adipose tissue (BAT) in response to cold exposure (present in infants, not reliably demonstrated in adults).

Question 115

Diet-induced thermogenesis

Answer 115

an increase in heat production as metabolism increases during food intake and digestion.

Question 116

Radiant heat gain

Answer 116

heat emitted from sources NOT in contact with the body (the sun, fire, a room full of other individuals who are radiating heat, etc).

Question 117

Conductive heat gain

Answer 117

heat gained from warm surfaces touching the body (hot cup of coffee, heated blanket, cuddling with your dog/cat/etc.)

Question 118

2. Mechanisms of HEAT LOSS in the body:

Answer 118

a. Conductive heat loss b. Radiant heat loss c. Convective heat loss d. Evaporative heat loss

Question 119

Conductive heat loss

Answer 119

heat loss due to cold surfaces touching the body (e.g. holding a cold glass of water, a cold stethoscope diaphragm,, etc). Accounts for ~3% of heat loss.

Question 120

Radiant heat loss

Answer 120

the body emits the heat it produces as infrared rays to other surfaces without contacting them. (e.g. standing in a cold empty room, there is radiant heat loss from your body to the walls). Accounts for majority (~60%) of heat loss.

Question 121

Convective heat loss

Answer 121

transfer of heat to the air or water surrounding the skin. Air and water currents move warmed air/water away from the body and replace it with cool air/water so that there is continual heat loss. E.g. wind/breeze, going swimming in a cold pool). Accounts for ~15% of heat loss.

Question 122

Evaporative heat loss

Answer 122

evaporation of water from the skin surface (e.g. sweating, cold compress, etc) and via respiratory tract. Accounts for ~20% of heat loss at rest, but up to 85% during exercise).

Question 123

NOTE: radiant and convective heat loss are enhanced by

Answer 123

vasodilation in the skin.

Question 124

Body temperature is controlled by

Answer 124

reflex responses integrated in the thermoregulatory centre of the hypothalamus.

Question 125

The thermoregulatory centre receives

Answer 125

sensory input from peripheral thermoreceptors in the skin and central thermoreceptors in the anterior hypothalamus.

Question 126

In response to an increase in body temperature,

Answer 126

the hypothalamic thermoregulatory centre activates sympathetic CHOLINERGIC neurons that stimulate sweat glands to produce sweat, and stimulate VASODILATION of cutaneous blood vessels. The result is an increase in evaporative heat loss (sweat) and radiant/convective heat loss (vasodilation) that will return body temperature to within the homeostatic range.

Question 127

In response to a decrease in body temperature,

Answer 127

the hypothalamic thermoregulatory centre activates sympathetic ADRENERGIC neurons that stimulate VASOCONSTRICTION of cutaneous blood vessels and may stimulate NON-SHIVERING THERMOGENESIS in Brown adipose tissue (BAT). At the same time, somatic motor neurons to skeletal muscles are activated to produce SHIVERING THERMOGENESIS. The result is both a decrease in radiant/convective heat loss (vasoconstriction) as well as increase in heat production (shivering and possibly non-shivering thermogenesis) all of which will act to increase body temperature and return it to within the homeostatic range.

Question 128

In addition to the physiological responses that regulate body temperature, humans also use

Answer 128

behavioural responses to minimize changes in body temperature. For example, putting on a sweater when we are cold, or using a fan or air conditioning on a hot day.