Metabolic States & Thermoregulation Study Guide

What is metabolism? anabolism? catabolism?

Metabolism - the 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?

As food fuels are oxidized (lose oxygen), their energy is transferred to a series of other molecules and, eventually, ADP to form ATP.

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

Substrate-level phosphorylation
- high-energy phosphate groups are transferred directly from phosphorylated substrates (like glyceraldehyde 3-phosphate) 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 the mitochondria (location of 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 release during the oxidation of food fuels is used to pump protons across the inner mitochondrial space into the inter membrane space
- this creates concentration gradient for protons across the membrane

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

C6H12O6 + 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 is phosphorylated in the cytosol of the cell and is converted to fructose-1, 6-biphosphate. 2 ATP molecules are used to phosphorylate glucose.
2. Fructose-1, 6-biphosphate is split into two 3-carbon fragments (glyceraldehyde 3-phosphate or dihydroxyacetone phosphate)
3. The 3-carbon fragments are oxidized and 4 ATP molecules are formed.
4. NAD+ picks up the hydrogen.
5. The net gain is 2 ATP because two ATP molecules had to be broken down for glycolysis to begin.

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

When oxygen is present, NADH + H+ delivers the hydrogen atoms to the enzymes of the electron transport chain in the mitochondria, which delivers them to O2 for water formation.

However, when oxygen is not present in sufficient amounts, NADH + H+ unloads the hydrogen ions back onto pyruvic acid, which becomes 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?

The citric acid cycle occurs in the mitochondrial matrix.

Each turn of the TCA cycle produces two CO2 molecules, four molecules of reduced enzymes (3 NADH + 3H+ and 1 FADH2).

The cycle turns twice.

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?

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.
4. The protons escape into the watery matrix, only to be picked up and pump 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 -> H2O).
6. ATP synthase harnesses the energy of the proton gradient to synthesize ATP. As H+ flows back across the membrane through ATP synthase, the synthase rotor spins, causing Pi to attach to ADP, forming ATP

- inner membrane of mitochondria
- electrons split from hydrogen ion that come off NADH and FADH2
- O2 is final electron acceptor

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 at the end to be the final acceptors of hydrogen ions

6H2O - formed by combining the 6O2 and hydrogen ions

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

Define glycolysis, glycogenesis, glycogenolysis, and gluconeogenesis.

glycolysis - glucose to pyruvic acid
glycogenesis - formation of glycogen from glucose in liver and skeletal muscle (anabolic); occurs when glucose supplies exceed demand for ATP (glucose to glycogen)
glycogenolysis - glycogen converted to glucose in liver and skeletal MT (catabolic); stimulated by low blood glucose (glycogen to glucose)

gluconeogenesis - glycerol and AA converted to glucose when none is available (anabolic) (glycerol/AA to glucose)

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

Beta-oxidation: 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

Define lipolysis and lipogenesis.

Lipolysis - the breakdown of stored fats into glycerol and fatty acids
Lipogenesis - forms lipids from acetyl CoA and glyceraldehyde 3-phosphate

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 = ketones in urine from acetyl CoA conversion
metabolic acidosis - pH drops because ketones are acids, fruity from acetone, rapid breathing to blow off CO2 carbonic acid

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 each compartment in terms of metabolic interconversions.

Brain
- has a high & fairly constant energy and O2 demand
- does not like anaerobic respiration
- prefers glucose as a fuel
- can use ketone bodies if necessary during periods of prolonged fasting
- does not have any fuel reserves and cannot use fatty acids

Skeletal Muscle
- relies primarily on fatty acids
- stores glycogen and breaks it down when they need to
- GLUT4 is the glucose transporter and is unregulated by insulin
- at rest, energy needs are met largely by fatty acids
- during exercise, skeletal muscles rely more heavily on CHO to meet its energy needs

Heart (Cardiac Muscle)
- only does aerobic respiration (becomes ischemic if not)
- does not store glycogen or fats (picks up fuel from blood)
- can use lactate when available
- uses ketone bodies when desperate

Adipose Tissue
- GLUT4 can pick up glucose and make glycerol for triglyceride formation
- unlimited reserve of triglycerides
- prefers fatty acids

Liver
- central hub for nutrient processing and distribution
receives nutrients from hepatic portal system
- conversion of fuels
- high rate of blood flow to pick ups and release
- when fuels are abundant, the liver takes fatty acids to make lipoproteins; converts many fatty acids to ketone bodies during fasting
- CHO: hepatocytes mostly use glucose to build glycogen
- the rest is used for lipogenesis
- amino acids: can take them up when they are about to make plasma proteins
- liver can also catabolize them if we are starving or there are too many
- deamination: leaves carbon-based molecule for gluconeogenesis

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

Absorptive state - last about four hours after eating begins, when nutrients are flushing into the blood from the GI tract

Post-absorptive state - period when the GI tract is empty and body reserves are broken down to supply energy

Describe how CHO, fats, and proteins are utilized during each of the above states (#16).

absorptive
- CHO = glycogenesis, fat, energy
- fats = lipogenesis, energy for adipose, skeletal and cardiac
- proteins = AA are used in protein synthesis
post absorptive
- CHO = glycogenolysis (liver, skeletal), gluconeogenesis
- fats = lipolysis
- proteins = AAs converted to glucose

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

Absorptive
- 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)
- neural: parasympathetic activity

Post-Absorptive
- neural = sympathetic ANS epinephrine = glycogenolysis, lypolysis
- hormonal = glucagon = glycogenolysis, gluconeogenesis, lypolysis from fat; GH, tyroxine, sex hormone, corticosteroids

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.

- glycogenolysis in the liver (depleted after about 12 hours)
- 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, performs glycogenolysis and releases glucose to the blood
- gluconeogenesis converts amino acids and glycerol to glucose when glycogen stores are exhausted and blood glucose levels are falling
- 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.

At rest: stores fuel as glycogen and prefers fatty acids
During exertion: energy from carbohydrates, glycogenolysis or blood glucose made in liver by gluconeogenesis
absorptive - glucose uptake, glycogenesis post-absorptive - glycolysis

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

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?

in the resting body, most heat is generated in 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 (liver, heart, brain, etc.)

Shell - skin and surface temperature

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 is fairly constant. 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 - heat is transferred through infrared waves
Conduction - the transfer of heat from one surface to another through direct physical contact
Convection - the transfer of heat by the movement of the surrounding fluid, which may be either a liquid or gas
Evaporation - water evaporates when its molecules absorb sufficient heat to move them from the 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.

insensible heat loss accompanies insensible water loss from evaporation in mucosa, mouth, skin - 10-20% basal heat loss

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 the 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?

preoptic region

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

- constriction of cutaneous blood vessels:
- shivering: skeletal muscle activity produces large amounts of heat
- increase in metabolic rate: enhances heat production
- enhanced release of thyroxine: activates the release of TSG, which releases more thyroid hormone to the blood (heat production rises)

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
- enhanced sweating: to lose heat by evaporation

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

negative feedback, rising temperatures signal shut off in hypothalamus positive in case of hyperthermia

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

hyperthermia - ineffective heat loss depressing hypothalamus heat stroke - continuous increase in temperature leading to organ damage because we cannot effectively cool
hypothermia - low temperature from cold exposure and inability to generate heat

Distinguish between heat exhaustion and heat stroke.

heat stroke - increasing temperature 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 stroke

How does fever differ from other types of hyperthermia?

controlled hyperthermia- macrophages release pyrogens which act on hypothalamus to increase temp by vasoconstriction and shiverring- temp lowers when macrophages no longer eat infection and pyrogens don't act on hypothalamus

transamination

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

ketone bodies

the by-products of the incomplete breakdown of fat

ketogenesis

creation of ketone bodies

Deamination

the removal of an amino group from an amino acid

GLUT-4

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

thermoregulation

Process of maintaining an internal temperature within a tolerable range.

heat of vaporization

The amount of energy required for the liquid at its boiling point to become a gas

hypothermia

abnormally low body temperature

fever

elevated body temperature

hyperthermia

Abnormally high body temperature

heat exhaustion

a form of physical stress on the body caused by overheating

heat stroke

a dangerous condition in which the body loses its ability to cool itself through perspiration

glycogenesis

formation of glycogen from glucose

Glycogenolysis

breakdown of glycogen to glucose

Gluceoneogenesis

A metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates.

lipogenesis

the metabolic formation of fat

lipolysis

the breakdown of fats and other lipids by hydrolysis to release fatty acids