Metabolic States and Thermoregulation Study Guide

What is metabolism? anabolism? catabolism?

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

How do redox reactions provide energy for ATP production?

oxidation: Hydrogen atoms removed from compounds

reduction: Hydrogen atom added to compound

redox: as food fuels are oxidized, their energy is transferred to a series of other molecules and ultimately to ADP to form ATP

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

substrate-level phosphorylation:

- high-energy phosphate groups directly transferred from phosphorylated substrates (ie metabolic intermediates) to ADP

- occurs b/c high energy bonds attaching phosphate groups to the substrates are more unstable than those in ATP

- ATP synthesized twice during glycolysis and once during each turn of the citric acid cycle

- enzymes located in cytosol (where glycolysis is) and the watery matrix inside the mitochondria (where citric acid cycle is)

oxidative phosphorylation:

- releases most energy eventually captured in ATP bonds during cell respiration

- carried out by electron transport proteins embedded in the inner mitochondrial membranes

- chemiosmotic processes: couples the movement of substances across membranes to chemical reactions

- energy released during oxidation pumps protons into intermembrane space, creating a conc gradient across the membrane

- when H+ then flows back across the membrane through ATP synthase, gradient energy creates ATP

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

C6H12O6 (glucose) + 6O2 --> 6H2O + 6CO2 + 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.)

1. glucose phosphorylated twice in the cytosol, converting into fructose-1,6-bisphosphate

- uses 2 ATP to provide activation energy

2. fructose-1,6-bisphosphate split into two 3-carbon fragments that exist as either glyceraldehyde 3-phosphate or dihydroxyacetone phosphate

3. the two 3-carbon fragments are oxidized by the removal of H+ by NAD+, transferring some of glucose's energy to NAD+

- inorganic phosphate groups attached to each oxidized fragment by high-energy bonds

- when the terminal phosphates split off, four ATP molecules formed (substrate-level phsophrylation)

2 pyruvic acid and 2 net ATP formed

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

when oxygen readily available:

- NADH + H+ delivers H+ to the electron transport chain in the mitochondria

no sufficient oxygen:

- NADH + H+ unloads H+ back onto pyruvic acid, reducing it, yielding lactic acid

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?

occurs in the mitochondrial matrix

each turn of the cycle produces:

- two CO2

- four reduced coenzymes (3 NADH + 3H+ and 1 FADH2)

- one ATP via substrate-level phosphorylation

the cycle turns twice per glucose (two pyruvic acid made from one glucose)

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?

located at mitochondrial matrix inner mitochondrial membrane

steps:

1. reduced coenzymes (NADH and FADH2) deliver electrons to respiratory enzyme complexes I and II

- NADH + H+ and FADH2 become NAD+ and FADH+

2. electrons transferred from one complex to another in the membrane

- ea complex reduced and oxidized

- ea successive carrier has a greater affinity for electrons than the ones preceding it until it reaches oxygen (highest affinity)

- energy released pumps H+ into the intermembrane space, creating an electrochemical gradient b/w the matrix and the intermembrane space

- coenzyme Q and chytochrome c shuttle electrons b/w the larger complexes

3. at respiratory enzyme complex IV, two electrons combine w/ two protons and half molecules of O2 to make water

4. ATP synthase harnesses the energy of the proton gradient back into the cell, causing the synthase rotor to spin and attaching Pi to and ADP to form ATP

- conc gradient allows for pH gradient and voltage gradient

In the chemical reaction summarizing glucose catabolism 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).

6O2:

- used in the ETC to be the final acceptor of H+ and electrons

6CO2:

- 2 from transitional phase (from pyruvic acid turning into acetyle CoA) and 4 made in CAC (2 CO2 made per each turn of the CAC)

6H2O:

- made in the ETC by combining H+ and O2

Define glycolysis, glycogenesis, glycogenolysis, and gluconeogenesis.

glycolysis: anaerobic breakdown of glucose to pyruvic acid that occurs in the cytosol

glycogenesis: glucose molecules combined into glycogen after high ATP levels turn off glycolysis

glycogenolysis: glycogen splitting when blood glucose drops

gluconeogenesis: process of forming new glucose from noncarbohydrate molecules in the liver

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

beta-oxidation: the initial phase of fatty acid oxidation that converts fatty acids to acetyl CoA

- occurs in the mitochondria

the acetyl-CoA enters the citric acid cycle where it is oxidized into CO2 and H2O

Define lipolysis and lipogenesis.

lipolysis: the breakdown of stored fats into glycerol and fatty acids

- occurs when carb intake is inadequate

lipogenesis: formation of lipids from acetyl CoA and glyceraldehyde 3-phosphate

- occurs when blood sugar is high

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: occurs when large amounts of ketone bodies accumulate in the blood and are excreted in the urine

- common in starvation, diabetes mellitus, and carb restriction

- can lead to metabolic acidosis

metabolic acidosis: body's buffer systems can't tie up the acids (ketones) fast enough, causing blood pH to drop to dangerously low levels

- person's breath smells fruity and breathing becomes more rapid

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

- brain/neural tissue

- skeletal muscle

- heart

- adipose tissue

- liver

- other peripheral tissue

Briefly describe the unique characteristics of the brain in terms of metabolic interconversions

1. high and constant energy and O2 demand

- 20% of resting oxygen consumption goes to the brain

- needs a constant flow of blood and oxygen to be maintained

2. prefers glucose as fuel reserve

- 60% of resting glucose consumption

- can't use fatty acids as fuel (does not cross blood brain barrier b/c they attach to albumin and are too big)

- has a GLUT transporter that acts independent of insulin for neural uptake of glucose

3. doesn't have fuel reserves

- picks up glucose for immediate use

- neurons have GLUT-3 transporters in plasma membrane that always work as long as concentration gradient is maintained

4. can use ketones during periods of prolonged fasting and starvation

- not sustainable, increased fatty acid breakdown by the liver when there is starvation or vigorous exercise

- will see brain fog and confusion when the ketones are the main form of fuel

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

absorptive state (fed state): lasts about four hours after eating begins when nutrients are flushing into the blood from the GI tract

- anabolism exceeds catabolism and nutrients are stored

- increased blood glucose, amino acids, and fatty acids

- glucose converted into glycogen; amino acids into proteins; glycerol and fatty acids into triglycerides

postabsorptive state (fasting state): period when the GI tract is empty and body reserves are broken down to supply energy

- can last 12-15 hours after absorptive state

- gluconeogenesis by the liver

- glycogenolysis by the skeletal muscle

Describe how CHO, fats, and proteins are utilized during the absorptive state

absorptive state:

CHO:

- absorbed monosacc directly delivered to the liver where fructose and galactose converted into glucose

- glucose released to blood or converted to glycogen and fat

- glycogen stored by liver

- glycogenesis, fat, energy

fats:

- lipogenesis, energy for adipose, skeletal and cardiac

- triglycerides hydrolyzed to fatty acids and glycerol to be used as an energy source for adipose cells, skeletal and cardiac muscle cells, and liver cells

- most fatty acids and glycerol are reconverted to triglycerides and stored

proteins:

- deaminated into keto acids by liver

- can be used for ATP synth or converted to liver fat stores

- can be used to synth plasma proteins

- most remain in the blood for uptake by other body cells for prot synth

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

hormonal control of absorptive:

- directed by insulin

- increased blood glucose, amino acid levels, glucose-dependent insulinotropic peptide (GIP), gastrin, CCK stimulate and promote beta cells release of insulin

neural control of absorptive:

- parasympathetic stimulation promotes insulin release

hormonal control of postabsorptive:

- glucagon stimulated by declining glucose levels

- glucagon targets liver and adipose where hepatocytes respond by accelerating glycogenolysis and gluconeogenesis

- adipose cells undergo lipolysis and release fatty acids and glycerol into blood

- protein intake increases amino acid levels which trigger both insulin and glucagon

-growth hormone, thyroxine, sex hormones, and corticosteroids influence metabolism and nutrient flow

-growth hormone exerts anti-insulin effects

neural control of postabsorptive:

- adipose supplied by sympathetic neurons

- epinephrine released by adrenal medulla in response to sympathetic activation on the liver, skeletal muscle, and adipose tissues

- sympathetic activation mobilizes fat and promotes glycogenolysis

- can be activated by injury, anxiety, mobilization of the fight or flight response

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

insulin

List insulin's metabolic effects.

- stimulate up-regulation of GLUT-4

- enhances glucose oxidation for energy

- stimulates glycogenesis, lipogenesis, and protein synthesis

- inhibits gluconeogenesis and release of glucose into the blood

- increases active transport of amino acids

Describe the regulation of metabolism during the postabsorptive state.

regulated toward either making glucose available in blood or sparing glucose for use by organs that need it most (brain)

- inhibits insulin release

- releases glucagon to accelerate glycogenolysis and gluconeogenesis

- glucagon also enhances glucose and fatty acid levels, mobilizing fat and converting it to ketone bodies

- release of epinephrine and sympathetic activation mobilize fat and promote glycogenolysis

- cortisol stimulates gluconeogenesis and blocks glucose uptake

- growth hormone exerts anti-insulin effects

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

- converts galactose and fructose into glucose

- stores glucose as glycogen and performs glycogenolysis, releasing glucose into blood

- converts amino acids and glycerol to glucose when glycogen stores are exhausted and blood glucose levels are falling

- break down amino acids into keto acids for ATP generation or lipogenesis (absorptive) or gluconeogenesis (postabsorptive)

- converts glucose to fats for storage (exportation of VLDLs to adipose tissue)

- converts fatty acids into ketones for fuel and export

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

at rest:

- energy needs are met via fatty acids

- uses GLUT-4 to take up glucose

- builds glycogen

exertion:

- relies more heavily on carbs

- glycogenolysis

- slow twitch uses FA more than fast twitch can

- generates pyruvic acid/lactate (which can be used in liver/cardiac muscle)

absorptive state:

- skeletal muscle mainly uses carbs

- glucose uptake

- glycogenesis

postabsorptive state:

- glycolysis

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

- to provide constant energy to the brain

- most tissues and organs need glucose constantly as an important source of energy

- low blood glucose can cause seizure, loss of consciousness and death

- long lasting elevation of glucose can result in blindness, renal failure, vascular disease

- hypoglycemia can lead to death → DKA due to use of ketone bodies as fuel

- hyperglycemia can lead to kidney problems, nerve damage, heart attack, etc.

Where in the resting body is most heat generated?

at rest: liver, heart, brain, kidneys, and endocrine

- inactive skeletal muscles accounting for only 20-30%

when shivering, skeletal muscles can produce 30-40X more heat than the rest of the body

Name and locate the body's thermal compartments.

core: organs in the skull, thoracic, and abdominal cavities

shell: skin and surface tissues

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

the core temperature is precisely regulated via blood

the shell experiences greater temperature variability

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

radiation:

- loss of heat in the form of infrared waves (thermal energy)

- any object warmer than its environment will transfer heat to those objects

- close to 1/2 of your body heat loss occurs via radiation

conduction:

- transfers heat from a warmer object to a cooler one when the two are in direct contact w/ ea other

- EX: step into a hot tub, some of the heat of the water transfers to your skin

convection:

- transfer of heat that occurs b/c warm air expands and rises and cool air falls

- enhances heat transfer from the body surface to the air b/c cooler air absorbs heat by conduction more rapidly than already-warmed air

- enhanced by wind or fan (more rapid movement of air across the skin)

evaporation:

- molecules of water absorb heat from the environment and escape as a gas

- every gram of water that evaporates removes about 0.58 kcal of heat from the body

Which of the physical mechanisms for heat transfer accounts for most of the heat lost under normal resting conditions?

radiation

Which heat transfer mechanism is dependent on relatively low ambient humidity?

evaporation

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

insensible water loss: unnoticeable water loss that occurs due to the continuous evaporation of water from the lungs, oral mucosa, and skin

- leads to insensible heat loss

insensible heat loss: dissipates abt 10% of the basal heat production of the body and is a constant not subject to body temperature controls

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

receptors:

- peripheral thermoreceptors in the shell (free dendritic endings that sense enviro)

- central thermoreceptors in the core (walls of BVs and pre-optic region of the hypothalamus that sense blood temp)

integration center: hypothalamus (particularly the anterior region)

- heat-loss center located more anteriorly

- heat-promoting center

efferent fibers: ANS motor fibers

effectors:

- sweat glands

- skin blood vessels

- skeletal muscles

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

pre-optic region (located in the anterior portion of the hypothalamus)

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

constriction of cutaneous blood vessels:

- sympathetic vasoconstrictor fibers activate and constrict BVs serving skin

- heat loss from core to shell dramatically lowered

- shell temp close to external environ

shivering:

- triggered when hypothalamus activates brain centers that cause increase in muscle tone

- stretch receptors alternately stimulated in antagonistic muscles

- skeletal muscle activity produces large amounts of heat

increase in metabolic rate (chemical thermogenesis):

- cold increases sympathetic stimulation of the adrenal medulla, releasing epinephrine and norepinephrine

- elevates metabolic rate and enhances heat production

enhanced release of thyroxine:

- infants release TRH that releases TSH to release TH, raising metabolic rate

- not in adults

Identify and describe the body's heat loss mechanisms.

dilation of cutaneous BVs:

- inhibits vasomotor fibers serving BVs of the skin allows vessels to dilate

- shell loses heat via radiation, conduction, and convection

enhanced sweating:

- evaporation necessary if body extremely overheated

- sympathetic fibers activate sweat glands to spew out large amounts of sweat

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

negative feedback

- rising temperatures signal shut off in hypothalamus

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

hyperthermia: overexposure to hot and humid environment renders normal heat-loss processes ineffective

- creates positive feedback cycle at around 41 C as increasing temps increase metabolic rate which increases heat production

- heat stroke: skin hot and dry; organs can be damaged

- heat exhaustion: dehydration and low BP w/ depressed heat-loss mechanisms

hypothermia: low body temps from prolonged uncontrolled exposure to cold

- decreased vital signs w/ sluggish enzymes

- drowsiness

- stopping of shivering at 30-32 C b/c body has exhausted heat-generating capabilities

- can progress to coma and death

Distinguish between heat exhaustion and heat stroke.

heat exhaustion: heat-associated extreme sweating and collapse of an indiv during or following vigorous physical activity

- elevated body temp and mental confusion

- due to dehydration and low BP

- can lead into heat stroke

heat stroke: skin becomes hot and dry; organs can damage

- creation of a positive feedback loop as increasing temps increase metabolic rate which increases heat production

- must immerse body in cool water and administer fluids

How does fever differ from other types of hyperthermia?

fever: controlled hyperthermia that typically results from infection, cancer, allergic reactions, or CNS injuries

- macrophages and other cells release cytokines acting as pyrogens that cause the release of prosta-glandins that reset the hypothalamic thermostat to a higher-than-normal temp

- heat loss from the body surface declines, skin cools, and shivering begins, generating heat

- temps rise to reach new setting and maintained until disease process is reversed

- reversal allows for heat-loss mechanisms to begin

Briefly describe the unique characteristics of the skeletal muscle in terms of metabolic interconversions

1. half of the body's mass, has large impact in metabolism

- relies on fatty acid (resting fuel) and glucose (exercise fuel)

- stores glycogen

2. GLUT-4 is glucose transporter and upregulated by insulin

- one of 2 tissues that express GLUT-4 (and adipose)

- when blood glucose increases, insulin increases, GLUT-4 causes more uptake of glucose by muscles

3. resting skeletal metabolism works differently from working muscle

a. at rest, energy needs met with fatty acids

- some glucose is taken up and used but most used to make glycogen for conservation and usage only by skeletal muscle

b. during exercise, muscles rely on CHO

-need more ATP

-white fibers need energy through aerobic metabolism

- start to break down proteins if needed to use amino acids for energy

- generates lactate when glucose is used (glycolysis is so fast, excess pyruvate forms lactate which the liver picks up for gluconeogenesis)

Briefly describe the unique characteristics of the heart in terms of metabolic interconversions

- high concentration of mitochondria, blood supply b/c it only aerobic metabolism (quickly ischemic)

- no fuel stores (no glycogen), picks up fuel from blood, needs a continuous supply of blood

- glucose and fatty acid --> prefers fatty acids

- picks up lactate if needed

- ketone bodies used if desperate

Briefly describe the unique characteristics of the adipose tissue in terms of metabolic interconversions

- stores reserve of energy in form of triglycerides

- prefers fatty acids

- can hydrolyze triglycerides, generating glycerol (used by the liver to make glucose) and fatty acids (that can be picked up by other cells as fuel)

GLUT-4 transporter:

- uses glycerol in glucose to build triglycerides (storage)

- glycerol used for gluconeogenesis in the liver

Briefly describe the unique characteristics of the liver in terms of metabolic interconversions

- central hub of nutrient distribution

- hepatic portal circulation delivers nutrient rich blood for anabolism and catabolism

- takes up 1/2-2/3 of needed glucose during digestion

carbohydrates:

- hepatocytes take in glucose from blood via diffusion to perform glycogenesis

- will perform glycogenolysis when the blood glucose levels drop

- if there's an excess of carbs, will make fatty acids out of glucose

lipids:

- performs lipogenesis

- packs lipids and fatty acids into VLDLs to be released into the blood for fuel

- during fasting/starvation, liver converts fatty acids into ketones to be exported into the blood as fuel

amino acids:

- in well-fed state, liver takes up amino acids for protein synthesis to make plasma proteins and help with liver repair

- catabolizes amino acids via deamination where the amine group is excreted

- C-backed cell catabolized to make ATP or gluconeogenesis or lipogenesis

Briefly describe the unique characteristics of the other peripheral tissues in terms of metabolic interconversions

- picks up what is readily available

- glucose, fatty acids, ketone bodies

Describe how CHO, fats, and proteins are utilized during the postabsorptive state

CHO:

- glycogenlysis in the liver where liver's glycogen stores are broken down

- glycogenolysis in skeletal muscle where glucose is partially oxidized to pyruvic acid and reconverted to glucose by the liver

- gluconeogenesis

fats:

- lipolysis in adipose tissues and liver that produces glycerol that is converted into glucose in the liver

proteins:

- cellular protein catabolized into blood glucose

VLDL

transport triglycerides from the liver to peripheral (nonliver) tissues, mostly to adipose tissues

refed state (not in study guide but she mentioned it in lecture)

when your liver and skeletal muscle replenishes glycogen storage after sleep (postabsorptive state prolonged)