METABOLIC STATES & THERMOREGULATION- LECTURE EXAM 3

Metabolism

sum of all the biochemical reactions in the body

Anabolism

all reactions that build larger molecules or structures from smaller ones

Catabolism

all processes that break down complex structures to simpler ones

• Ex. the hydrolysis of food in the digestive tract

How do redox reactions provide energy for ATP production?

• As food fuels are oxidized (GAIN OXYGEN), their energy is transferred to a series of other molecules and, eventually ADP to form energy rich ATP 

• Oxidation: the gain of oxygen or loss of hydrogen 

  • Whichever way oxidation occurs, the oxidized substance always loses (or nearly loses) electrons as they move to (or toward) a substance that more strongly attracts them

Explain the difference between substrate-level phosphorylation and oxidative  phosphorylation.

SUBSTRATE LEVEL PHOSPHORYLATION 

• High energy phosphate groups are transferred direction from phosphorylated substrate to ADP 

• Occurs because the phosphate groups are more unstable than ATP 

• ATP is synthesized in this route twice during glycolysis and once during each turn of the citric acid cycle 

• Enzymes involved are located in the cytosol (where glycolysis happens) and the matrix of mitochondria (location of the citric acid cycle)

  OXIDATIVE PHOSPHORYLATION

  • Releases most of the energy eventually captured in ATP bonds during cellular respiration 

  • Carried out by electron transport proteins embedded in the inner mitochondrial membranes

  • An example of a chemiosmotic process (the movement of substances across membranes to chemical reactions) 

  • Some of the energy released during the oxidation of food fuels is used to pump protons across inner mitochondrial space into the inter mem. Space

  • This creates a concentration gradient for protons across mem.

Write the chemical reaction that summarizes the complete catabolism of glucose.

Glucose + 6oxygen → 6water+6carbondioxide + 32 ATP + heat

Summarize the important events and products of glycolysis. (Include in your answer where in the cell glycolysis occurs and be sure to explain why the net gain of ATP is 2  rather than 4

LOCATION: cytosol of cell

1. Sugar activation 

   1. Glucose is phosphorylated twice and converted to fructose- 1,6- bisphosphate 

   2. USE TWO ATP MOLECULES (to be recouped later) which provides activation energy needed to prime the later stages of pathway 

   3. INVESTMENT PHASE 

2. Sugar cleavage

   1. Fructose- 1,6- bisphosphate is split into 3-carbon fragments that exist as one of the two isomers- glyceraldehyde 3-phosphate or dihydroxyacetone phosphate 

3. Sugar oxidation and ATP formation 

   1. 3 carbon fragments are oxidized by the removal of hydrogen, which NAD + picks up 

   2. Some of glucose’s energy is transferred to NAD+ 

   3. Inorganic phosphate groups (Pi) are attached to each oxidized fragment by high-energy bonds 

   4. Later when these terminal phosphate groups are split off, enough energy is captured to form 4 ATP molecules 

PRODUCTS: 2 pyruvic acid, two molecules of reduced NADH, two H+. and 2 ATP

• 4 ATP produced, but they are consumed in phase I to activate reactions 

 What happens to pyruvate when O₂ is readily available? when O₂ is not present in  sufficient amounts?

When O2 is present, NADH + H+ delivers its burden of hydrogen atoms to enzymes of the electron transport chain in the mitochondria which deliver them to O2, forming water (H2O)

When O2 is not present in sufficient amounts (during exercise) → NADH + H+ unload its hydrogen atoms back onto pyruvic acid, REDUCING IT BECAUSE IT (PA) IS GAINING HYDROGEN ATOMS

• The addition of two hydrogen atoms back onto pyruvic acid yields lactic acid 

• Some of this lactic acid diffuses out of the cells and is transported to the liver for processing

WE GO TO CITRIC ACID CYCLE IF OXYGEN IS PRESENT

The citric acid cycle (also called the TCA cycle or Krebs cycle) begins with a 3-carbon  citric acid molecule undergoing a series of redox reactions that removes H atoms and  transfers them to the coenzymes NAD⁺and FAD. Where does the TCA cycle occur?  What are the products of each turn of the TCA cycle? How many times does the cycle  “turn” per glucose molecule?

LOCATION: mitochondrial matrix 

• Each turn of the krebs cycle produces 2 CO2, 4 molecules of reduced coenzymes (3 NADH + 3 H+ and 1 FADH2), one molecule of ATP -> MULTIPLY THIS BY 2 FOR 2 TURNS 

• Two cycles for one glucose molecule

Summarize the important events and products of the electron transport chain (ETC).  Where are the respiratory complexes of the ETC located? What is the energy source for  the proton pumps of the ETC? What is the final electron acceptor for the ETC?

USE O2 DIRECTLY 

1. Reduced coenzymes (NADH + H+ and FADH2) deliver electrons to respiratory enzyme complexes I and II, respectively

2. The hydrogen atoms that the reduced coenzymes deliver are quickly split into H= and e- 

3. The electrons are shuttled along the mitochondrial membrane from one complex to the next, losing energy with each transfer (REDUCED then OXIDIZED)

4. The protons escape into the watery matrix, only to be picked up and pumped across the inner mitochondrial membrane into the inter membrane space by one of the major respiratory enzyme complexes (I, III, or IV) 

5. Two electrons are delivered to half a molecule of O2, creating oxygen ions that strongly attract water (2H+ + 2e- + 1/2O2 -> H20) 

6. ATP synthase harnesses the energy of the proton gradient to synthesize ATP. As H+ flows back across the membrane through ATP synthase rotor spins, causing Pi to attach to ADP, forming ATP

LOCATION: inner membrane of mitochondria 

• Electrons split from hydrogen ion come off NADH and FADH2 

• O2 is final electron acceptor

PRODUCTS: water and 28 ATP

In the chemical reaction summarizing glucose catabolism (#4) you hopefully noted that  6 O₂ are used per glucose molecule and 6 H₂O and 6 CO₂ are produced per glucose.  Specifically identify the stage of catabolism related to these 3 molecules (i.e., CO₂, H₂O, and O₂).

• 6CO2: citric cycle: each pyruvic acid produces 3 CO2 molecules from decarboxylation (two from the regular turn and one from the transitional phase) 

• 6H2O: ETC: formed by combining 6O2 and hydrogen ions 

• 6O2: ETC: used as the final electron acceptors of hydrogen ions

Glycolysis

converts glucose to pyruvic acid

Glycogenesis

• Polymerizes glucose to form glycogen 

• Synthesizes glycogen from glucose

• Occurs when glucose supplies exceed demand for ATP 

• LIVER AND SKELETAL MUSCLE (anabolic)

Glycogenolysis

• Breaks down glycogen to form glucose monomers 

• Stimulated by low blood glucose 

• LIVER AND SKELETAL MUSCLE (catabolic)

Gluconeogenesis

forms glucose from noncarbohydrate precursors

• ANABOLIC 

Define beta-oxidation. What happens to the acetyl-CoA produced in beta-oxidation?

• BETA OXIDATION:

  • Location: MITOCHONDRIA 

  • The initial phase of fatty acid oxidation, which converts fatty acids to acetyl-CoA; the carbon in the beta position is oxidized each time a two-carbon fragment is broken off 

  • Acetyl CoA enters the citric acid cycle where it is oxidized to CO2 and H2O

Lipolysis

• the breakdown of stored fats into GLYCEROL AND FATTY ACIDS 

  • The fatty acids and glycerol are released to the blood, helping to ensure that body organs have continuous access to fat fuels for aerobic respiration

Lipogenesis

• forms lipids from acetyl CoA and glyceraldehyde 3-phosphate 

  • Triglyceride synthesis, occurs when cellular ATP and glucose levels are high 

  • Excess ATP leads to an accumulation of acetyl CoA and glyceraldehyde 3-phosphate, two intermediates of glucose metabolism that would otherwise feed into citric acid cycle 

  • When these two metabolites are present in excess, they are channels into triglyceride synthesis pathways

 When excess acetyl-CoA accumulates in the liver due to high rates of beta-oxidation, the liver converts the acetyl-CoA to ketones which diffuse into the blood. What types of metabolic states can be associated with ketosis?

KETOSIS: because most ketone bodies are organic acids, ketosis leads to METABOLIC ACIDOSIS. The body’s buffer system cannot tie up the acids (ketones) fast enough, and the blood pH drops to dangerously low levels 

• The breath smells fruity from ketones 

• Rapid breathing reduces blood carbonic acid by blowing off CO2 to try to force blood pH up 

Starvation 

Diabetes mellitus

Identify the basic tissue compartments that play key roles in metabolic interconversions  in the body.

• Brain/ neural tissue 

• Skeletal muscle (resting and during exertion) 

• Heart

• Adipose tissue 

• Liver

• Other peripheral tissue

Briefly describe the unique characteristics of each compartment (#14) in terms of  metabolic interconversions.

• Brain: 

  • Has high and fairly constant energy and oxygen demand

  • Prefers glucose as fuel 

  • Doesn’t have fuel reserves and requires CONTINUOUS SUPPLY OF GLUCOSE

    • Transported by GLUT3 transporter 

  • Can also use ketones during periods of prolonged fasting and starvation

• Skeletal muscle:

  • GLUT4 is the glucose transporter in skeletal muscle (UPREGULATED BY INSULIN) 

  • Resting: preferred fuel is fatty acids 

  • During exertion: preferred fuel is glucose 

    • Lactate exported 

• Heart muscle: 

  • Aerobic and can’t sustain oxygen debt 

  • Uses fatty acids as preferred fuel

• Adipose tissue: 

  • Stored at triglycerides 

  • Released as glycerol or fatty acids into the blood 

  • GLUT4 can pick up glucose and make glycerol for triglyceride formation 

• Liver: 

  • Stored as glycogen and triglycerides 

  • Uses amino acids, glucose, fatty acids

  • Exported as fatty acids, glucose, and ketone bodies  

Identify the two distinct metabolic states of the body and tell when each would  normally occur.

• ABSORPTIVE (fed) state 

  • Lasts about 4 hours after eating begins 

  • ANABOLISM EXCEEDS CATABOLISM 

  • Excess nutrients are stored as fats if not used 

• PRE ABSORPTIVE (FASTING) STATE 

  • The period when the GI tract is empty and body reserves are broken down to supply energy

  • CATBOLISM EXCEEDS ANABOLISM

Describe how CHO, fats, and proteins are utilized during ABSORPTIVE STATE

• CHO 

  • CHO is a major fuel source for all body cells 

  • Liver and skeletal muscle stored CHO as glycogen (glyconeogenesis) 

  • Liver and adipose tissue package excess CHO as TG/fat 

• FATS

  • Chylomicrons are hydrolyzed to fatty acids and glycerols before they can pass through capillary walls 

  • Most enter adipose tissue to be reconverted to triglycerides and stored 

  • Adipose cells, skeletal and cardiac muscle cells, and liver cells use triglycerides as primary energy source 

• PROTEINS

  • Absorbed amino acids delivered to the liver (an excess delivered here), which deaminates some of them to keto acids 

  • Liver uses amino acids to make plasma proteins, including albumin, clotting and transport proteins 

  • Most amino acids remain in blood for uptake by other cells to be synthesized to proteins

Describe how CHO, fats, and proteins are utilized during PRE ABSORPTIVE STATE

CHO

• Glycogenolysis in the liver: glycogen stores mobilized into blood glucose 

• Gluconeogenesis in skeletal muscle: begins after liver, and glucose produced must first be oxidized to pyruvic acid, reconverted to glucose by the liver, and then released to the blood again

• FATS

  • Adipose and liver cells produce glycerol by lipolysis, and liver converts glycerol to glucose (gluconeogenesis) -> when you wake up after taking a nap that immediately follows eating 

  • Fatty acids cannot be used to bolster glucose levels 

• PROTEIN

  • Become source of blood glucose during prolonged fasting

  • Cellular amino acids deaminated and converted to glucose in liver 

  • Kidneys also carry out gluconeogenesis and contribute as much glucose to blood as the liver

Identify the hormonal and neural regulation involved with each metabolic state.

• ABSORPTIVE (fed) state 

  • Hormonal

    • Insulin is the primary regulator 

    • Rising blood glucose levels are the main stimulus for insulin 

    • Elevated plasma amino acids; GI tract hormones (GIP, gastrin, CCK) 

    • Stimulate beta cells of pancreatic islets to secrete more insulin 

  • Neural

    • Parasympathetic activity 

• POSTABSORPTIVE (FASTING) state 

  • Neural 

    • Sympathetic ANS interacts with several hormones 

    • Epinephrine = glycogenolysis, lipolysis

      • Released by adrenal medulla 1stimulates liver, skeletal muscle, and adipose tissues to mobilize fat and promote glycogenolysis 

  • Hormonal

    • Glucagon= glycogenolysis , gluconeogenesis, lypolysis from fat; GH, tyrosine, sex hormone, corticosteroids 

    • Glucagon is a hyperglycemic hormone that targets liver and adipose tissue to accelerate glycogenolysis and gluconeogenesis 

    • Growth hormone, thyroxine, sex hormones, corticosteroids can influence metabolism and nutrient flow

What is the primary regulator of metabolic events during the absorptive state? 

Insulin

List insulin’s metabolic effects.

• Enhances glucose uptake 

• Increases amino acids uptake and protein synthesis

• Increases glycogenesis 

• Increases lipogenesis and decreases lipolysis in adipose tissue 

• Increases triglyceride synthesis and decreases ketogenesis

Describe the regulation of metabolism during the postabsorptive state.

• Glycogen is stored in the liver for when needed, glycogenolysis 

• Gluconeogenesis in the liver (rely on this for blood glucose once glycogen is depleted - amino acids or fatty acids

• Glycolysis in skeletal muscle- epinephrine stimulates glycogenolysis and lipolysis 

• Ketogenesis in the liver

In what ways does liver metabolism help in maintaining normal blood glucose levels?

• It converts galactose and fructose to glucose 

• Stores glucose as glycogen when blood glucose levels are HIGH 

• In response to hormonal controls, it performs glycogenolysis and releases glucose to the blood 

• Gluconeogenesis converst amino acids and glycerol to glucose when glycogen stores are exhausted and blood glucose levels fall 

• Converts glucose to fats for storage 

Compare/contrast the metabolic profile of skeletal muscle under the following  conditions: during rest vs. exertion; absorptive state vs. postabsorptive state.

• Rest: relies on fatty acids

• Exertion: relies on glucose/ carbs 

• Absorptive state: decrease blood glucose levels by glycogenesis 

• Postabsorptive state: increases blood glucose levels by glycolysis

Why is it important to maintain a homeostatic plasma glucose level?

To provide constant energy to the brain; glucose is energy, too low can cause issues, as can too high, so it needs to be maintained

Where in the resting body is most heat generated?

Brain, heart, liver, kidneys, endocrine organs (inactive skeletal muscles only account for 20-30%)

Name and locate the body’s thermal compartments.

• CORE- deep body tissues like liver, heart, brain, etc. 

  • Organs within the skull and thoracic and abdominal cavities 

  • Has the highest temp 

• SHELL- skin and surface tissue of the body (LOWER TEMP THAN CORE)

  • Variable temp but always lower than core

Which of the above compartments (#26) maintains a fairly constant temperature (i.e.,  its temperature is precisely regulated)? Which experiences the greater temperature  variability?

• Core temp: stays constant

• Shell temp: fluctuates

Identify and describe the four physical mechanisms by which heat is  transferred/exchanged between the body and the surrounding environment.

• RADIATION : heat is transferred through infrared waves

  • Radiant energy travels from warm → cool 

  • Cold initially, as we sit radiating we get warmer 

  • Can gain or lose heat through radiation 

  • About 50% of heat lost at rest is through radiation 

• CONDUCTION: the transfer of heat from one surface to another through direct physical contact 

  • Sitting on chair 

• CONVECTION: the transfer of heat by the movement of surrounding fluid, which may be either a liquid or gas  

  • Heat exchange requires that one of the media be moving 

  • Convection substantially enhances heat transfer from the body surface to the air because cooler air absorbs heat by conduction more rapidly than the already warmed air 

• EVAPORATION: water evaporates when its molecules absorb sufficient heat to move them from liquid to gas state 

Which of the above mechanisms (#28) accounts for most of the heat lost under normal  resting conditions?

Radiation

Which mechanism (#28) is dependent on relatively low ambient humidity?

Evaporation

Describe insensible heat loss and its contribution to heat loss from the body.

• The noticeable water loss occurring via these routes, the accompanying heat is insensible heat loss 

• Insensible heat loss dissipates about 10% of the basal heat production of the body and is a constant not subject to body temperature controls 

• Evaporative heat loss becomes an active or sensible process when body temperature rises and sweating produces increased amount of water for vaporization 

• Mouth, skin, mucosa

Name and locate the components of the feedback system that regulates body  temperature.

• Temperature sensors: peripheral thermoreceptors over the skin surface and central thermoreceptors located internally 

• Afferent nerve fibers: thalamic pathways that travel to the cerebral cortex 

• Control center: in hypothalamus 

• Efferent nerve fibers

• Thermal effectors: sweat glands, skin blood vessels, and skeletal muscles

What region of the hypothalamus serves as the main integration center for afferent  input from the peripheral and central thermoreceptors?

Thermoregulatory centers (preoptic region)

• Heat loss center

• Heat promoting center

 Identify and describe the body’s heat-promoting mechanisms.

• Constriction of cutaneous blood vessels 

  • Activation of sympathetic vasoconstrictor fibers serving the blood vessels of the skin causes strong vasoconstriction 

  • Restrict blood to deep body areas and largely bypasses the skin 

  • Because a layer of insulating subcutaneous fatty tissue separates the skin from deeper organs, heat loss from the core through the shell is dramatically lowered 

• Shivering: skeletal muscle activity produces large amounts of heat

  • When muscle tone reaches sufficient levels, stretch receptors are alternately stimulated in antagonistic muscles 

• Increase in metabolic rate: enhances heat production

  • Cold increases sympathetic stimulation of the adrenal medulla, releasing epinephrine and norepinephrine 

  • These hormones elevate the metabolic rate and enhance heat production. This mechanism, called chemical (nonshivering) thermogenesis, occurs primarily in infants 

  • Small deposits of brown adipose tissue, a special kind of adipose tissue that dissipates energy and produces heat by this mechanism, are also found in adults 

• Enhanced release of thyroxine: activates release of TSG, which releases more thyroid hormone to blood (heat production rises) 

  • When environmental temp decreases gradually, as in the transition from summer to winter, the hypothalamus of infants releases TSG 

  • This hormone activates the anterior pituitary to release TSH, which induces the thyroid to liberate more thyroid hormone

 Identify and describe the body’s heat loss mechanisms.

• Dilation of cutaneous blood vessels: the shell loses warmth from the blood by radiation, conduction, and convection 

  • Inhibiting vasomotor fibers sebring blood vessels of the skin allows the vessels to dilate 

  • As the blood vessels swell with warm blood, the shell loses heat by radiation, conduction, and convection 

• Enhanced sweating: to lose heat by evaporation 

  • Sympathetic fibers activate the sweat glands to spew out large amounts of sweat

Is thermal balance maintained via positive or negative feedback? Explain.

Negative feedback: rising temps signal shut off in hypothalamus positive in case of hyperthermia

Identify and describe the basic homeostatic imbalances in body temperature  homeostasis.

• Hypothermia (COLDDDDD) 

  • Low core body temperature due to prolonged uncontrolled exposure to cold temperature 

    • Heat loss via conductivity/convection in cold water is much greater in water than in air 

  • Vital signs decreases as enzymes progressively work less effectively 

  • Ultimately unconsciousness results, progresses to coma, and finally death due to cardiac arrest 

  • Accidental hypothermia due to prolonged exposure to cold air or water is a serious condition leading to frostbite of exposed body parts

    • Ice crystals in interstitial fluid causing osmotic imbalance 

    • Cells shrivel, O2 deprive, tissue dies 

• Hyperthermia (HOTTTTT) 

  • Most commonly results from prolonged exposure to heat and high relative humidity 

  • We lost the ability to transfer heat via radiation and conduction/convection (leaves only evaporation as means of heat loss from body) 

  • Ineffective heat loss depressing hypothalamus

  • Heat stroke- continuous increase in temp leading to organ damage because we cannot effectively cool

Distinguish between heat exhaustion and heat stroke.

• Heat stroke: increasing temp shuts off hypothalamus feedback and heat control mechanisms are SUSPENDED

• Heat exhaustion: extreme sweating and collapse after activity from dehydration and low BP, heat loss mechanisms STRUGGLE and can lead to a stroke but not yet one

How does fever differ from other types of hyperthermia?

• FEVER: 

  • Regulated elevation of core temps resulting from infection or disease caused by circulating cytokines called pyogenes 

  • Release prostaglandins (reset set point) 

  • Body thinks it's cold so promotes heat promoting mechanisms 

  • Fever breaks when sweating because set point goes back to normal 

  • Body initiates cooling 

• Represents an increase in the hypothalamic set point for temp regulation 

• Results in the body initiating heat promoting mechanisms (i.e vasoconstriction of subcutaneous blood vessels)

Deamination

 the removal of an amino group from an amino acid

Transamination

The process by which an amino group from one amino acid is transferred to a carbon compound to form a new amino acid.

GLUT-4

Important in muscle and adipose tissue for glucose transport across muscles and triglyceride storage by lipoprotein lipase activation

ketone bodies

the by-products of the incomplete breakdown of fat