Cellular Bio - Energetics

Appetite & Satiety

(Cellular Bio - Energetics)

• Control of food intake is a complex process

• Two competing behavioral states

  • Appetite - hunger

  • Satiety - feeling full/satisfied

What are the two hypothalamic centers?

(Cellular Bio - Energetics)

• Feeding center: Tonically activate (active when hungry)

• Satiety center: Inhibits feeding center (you’re not hungry)

What is the glucostatic theory?

(Cellular Bio - Energetics)

• The satiety center has neurons called glucostats that rapidly absorb blood glucose after a meal

• Hypothesis: Glucose uptake causes the satiety center to send inhibitory signals to the hunger center and thus suppresses appetite

What is the lipostatic theory?

(Cellular Bio - Energetics)

• Body fat content is maintained for homeostasis

• When energy balance is positive, fat increases

• Leptin release (from fat cells)

• Leptin feeds back to the brain to decrease energy storage

  • Don’t need anymore energy - enough is stored

Explain the process of peptide regulation.

(Cellular Bio - Energetics)

1. Neuropeptide Y: Hunger-stimulating peptide made in the hypothalamus, which activates the hypothalamic feeding center

2. When the feeding center is activated

↑ Food intake

↑ Fat stores

↑ Leptin secretion (leptin comes from fat cells)

3. Leptin then feeds back to the brain and:

   • Inhibits NPY

   • Suppresses the feeding center

   • Part of a negative feedback loop

     • ↑ Fat, ↑ Leptin, less hunger/eat less

How does the gut communicate with the brain to regulate hunger and satiety?

KEY TAKEAWAY: Food intake isn’t regulated by just one hormone or one brain center. It’s influenced by mechanical signals, nerves, hormones, and reward pathways all at once.

• Nerve signals (blue dashed line – vagus nerve)

  • Stomach distension (stretching when you eat → “I’m full”)

  • Changes in gut movement/pressure
    These travel quickly to the hindbrain and hypothalamus.

  • Ghrelin from the stomach - induce hunger

• Hormones in the bloodstream (red line)

  • Ghrelin from the stomach → signals hunger

  • Satiety hormones like GLP-1 from intestines → signal fullness
    These circulate in blood and act on the brain.

The brain areas involved:

• Hypothalamus – homeostatic control (energy balance)

• Hindbrain – basic feeding control

• Reward center – pleasure/motivation to eat

How do we do work?

Eating!

• First law of thermodynamics (conservation of energy)

• Change in energy = Energy intake - Energy Output

• Energy Intake = Diet

• Energy Output = Work + Heat

• Work: Transport, Mechanical, Chemical

How do we intake energy?

Through food (energy)!

• Direct calorimetry'

  • Fat - 9 kcal/g

  • Protein 4 kcal/g

  • CHO (carbohydrate) - 4 kcal/g

• Energy of Absorption

• Digestive Waste

Energy Output

• By mass balance: Output = Intake - Heat

• Indirect calorimetry

  • Oxygen consumption

  • CO₂ production

  • Respiratory Quotient (indicates what fuel source is being used)

    • 1 - CHO

    • 0.8 - Protein

    • 0.7 - Fat

    • 6 kcal/L O₂ (RQ = 1)

• Metabolic Rate - L O₂/day x kcal/L O₂

What are the factors that contribute to the basal metabolic rate?

• Age and sex

• Lean Body Mass

• Hormones

• Genetics

• Activity/diet level

• Thermic effect of eating

  • How often you eat

  • How much heat is released from digestion

How is glucose (from blood or glycogen) converted into usable energy?

Through the process of glycolysis!

• Fed state

• Occurs in cytoplasm

• Glucose enters the cell and becomes G6P

  • This glucose comes from blood glucose or glycogen (stored glucose)

• Glucose goes through glycolysis to become pyruvate

• Anaerobic pathway: becomes lactate

• Aerobic pathway: enters mitochondria

Explain the steps of aerobic metabolism

• Takes place in the mitochondria (aerobic metabolism)

• Pyruvate → Acetyl-CoA

• Fatty acids are broken down by beta oxidation → Acetyl-CoA

• Acetyl-CoA enters citric acid cycle

  • Produces CO2 and high energy electrons from NADH and FADH₂

• Electrons → ETC → lots of ATP + H₂O

• Excess acetyl-CoA in liver → ketone bodies

How does the body make glucose during fasting?

Through gluconeogenesis (fasting state)!

• Occurs in liver & kidney

• Lactate, amino acids → pyruvate

• Pyruvate + amino acids + glycerol → G6P → Glucose (liver/kidney(

• Maintains blood glucose when intake is low

How many net ATP are produced through anaerobic metabolism?

2 ATP

How many net ATP are produced through aerobic metabolism?

30-32 ATP

(26-28 from ETC)

Explain the process of lipid anabolism

Fat synthesis consists of two parts:

Explain the process of lipid catabolism.

1. Triglycerides are broken down

   • Enzymes called lipases split a triglyceride into:

     • 1 glycerol

     • 3 fatty acids

2. Glycerol enters glycolysis

   • Glycerol becomes pyruvate and is used to make ATP

3. Fatty acids enter the mitochondria

   • Inside, they undergo β-oxidation

   • This process chops fatty acids into 2-carbon units

4. 2-carbon units → Acetyl-CoA

   • Each unit becomes acetyl-CoA

   • Acetyl-CoA enters the citric acid cycle

   • → produces CO₂, high-energy electrons

   • → feeds the ETC to make lots of ATP

What happens to amino acids during deamination, and why must ammonia be converted to urea?

• Deamination: Amino group from an amino acid is removed to produce ammonia and an organic acid, which then enters glycolysis or the citric acid cycle

• Ammonia is toxic, which is why it is converted to urea

What is the fed state?

• Absorptive

  • Energy absorbed and stored

  • Ingested molecules (from food)

    • Used in energy

    • Used in synthesis

    • Stored

  • Anabolism - builds complex molecules required for bodily processes

What is the fasted stated?

• Energy used

• Catabolism - breaks down nutrients/molecules for energy

What are the three fates of ingested biomolecules?

1. Energy to do mechanical work

2. Synthesis for growth and maintenance

3. Storage as glycogen and fat

How do alpha, beta, and delta cells in the pancreatic islets (cluster of cells) interact to regulate blood glucose?

• Alpha cells (green) → secrete glucagon

• Beta cells (purple) → secrete insulin

• Delta cells (brown) → secrete somatostatin

• Note: F cell produces pancreatic polypeptide

• Beta cells predominate (60-80%)

• Cells linked by tight junctions

  • Regulated entry of small molecules

• Blood flows from beta to alpha and delta cells (BAD)

• Beta cell is primary glucose center

Diagram:

• Beta cells → Insulin

  • Lowers blood glucose

  • Inhibits alpha cells (↓ glucagon release)

• Alpha cells → glucagon

  • Raises blood glucose

  • Stimulates beta cells → ↑ insulin release

  • Stimulate delta cells → ↑ somatostatin

• Delta cells → somatostatin

  • Alpha cells → ↓ glucagon, ↓ blood glucose

  • Beta cells → ↓ insulin, ↑ blood glucose

What is the function of glucagon?

• Source: alpha cell (pancreas)

• Target Tissues: Liver (adipose, skeletal muscle)

• Action: Promotes glycogenolysis (breaking down stored glycogen into glucose-1-phosphate and glucose in the liver and muscles) and gluconeogenesis in the liver

What is the function of insulin?

• Source: beta cell (pancreas)

• Target Tissues: Liver (adipose, skeletal muscle)

• Action: Promotes uptake of glucose, amino acids, and fatty acids from blood into cells for storage as glycogen, protein, and triglyceride

What is the function of somatostatin?

• Source: Delta cell (pancreas), GI tract, hypothalamus

• Target tissues: Other islet cells, GI tract, brain, and pituitary gland

• Action:

  • ↓ release of insulin and glucagon

  • ↓ GI tract motility

  • ↓ growth hormone secretion

What is the function of ephinephrine?

• Source: Adrenal medulla

• Target tissues: Many

• Action:

  • Promotes glycogenolysis in liver, lipolytic vis hormone-sens. Lipase

What is the function of cortisol?

• Source: Adrenal cortex

• Target tissues: Many

• Action: Antagonizes insulin action

Think of it being like a court (its arguing against insulin)

What is the function of GLP?

• Source: Ileum

• Target tissues: Pancreas, stomach, brain, heart

• Action:

  • ↑ beta cell mass and insulin secretion

  • Delays gastric emptying

  • ↓ food intake and glucagon secretion

What is the function of leptin?

• Source: Adipoctyes

• Target tissues: CNS (basomedial hypothalamus)

• Action:

  • Signals adequacy of energy stores (doesn’t need anymore)

  • ↓ food intake

What is glycogenesis?

The process of synthesizing glycogen (stores glucose)

What is glycogenolysis?

The process of breaking down glycogen to release glucose

What is gluconeogenesis?

The process of synthesizing glucose

What is glycolysis?

The process of utilizing glucose metabolically

Explain the glucose–glycogen metabolic see-saw.

When one process is running, the other isn’t

• Fed state (high blood glucose, insulin present)
  → The body wants to store glucose (so u need a large concentration of glycogen)
  → Glycogenesis is activated
  → Glycogenolysis is inhibited

• Fasting or stress (low blood glucose, glucagon/epinephrine present)
  → The body wants to release glucose
  → Glycogenolysis is activated
  → Glycogenesis is inhibited

At the enzyme level:

• Glycogen synthase = makes glycogen

  • Activated by insulin

  • Inhibited by glucagon/epinephrine (via cAMP, phosphorylation) → has stored enough glycogen

• Glycogen phosphorylase = breaks down glycogen

  • Activated by glucagon/epinephrine

  • Inhibited by insulin

Hormones control this “see-saw” through signaling pathways (cAMP, phosphorylation) so the cell never wastes energy building and breaking glycogen at the same time.

How is glucagon and insulin balanced?

Fed state:

• Insulin dominates

• ↑ Glucose oxidation

• ↑ Glycogen synthesis

• ↑ Fat synthesis

• ↑ Protein Synthesis

Fasted State:

• Glucagon dominates

• ↑ Glycogeneolysis

• ↑ Gluconeogenesis

• ↑ Ketogenesis

Before meal:

• ↑ Glucagon

• ↓ Glucose

• ↓ Insulin

After meal:

• ↓ Glucagon

• ↑ Glucose

• ↑ Insulin

Describe how insulin functions in the fed state.

How does insulin function in adipose and resting skeletal muscle (both fasted and fed state)?

Fasted state:

• No insulin - no GLUT4 transporters in the membrane

Fed state:

• Insulin signals the cell to insert GLUT4 transporters into the membrane, allowing glucose to enter the cell

1. Insulin binds to the receptor

2. Signal transduction cascade - GLUT4 transporters are produced

3. Exocytosis (transporter fuses with membrane)

4. Glucose enters the cell via the transporter

How does insulin function in liver hepatocytes (both fasted and fed state)?

Fasted state:

• The hepatocyte makes glucose and transports it out into the blood, using GLUT2 transporters

• Low insulin (doesn’t bind to receptor)

• High concentration of glucose (inside cell)→ glycogen stores and gluconeogenesis

Fed state:

• The glucose concentration gradient reverses and glucose enters the hepatocyte

• Hexokinase-mediated conversion of glucose to G6P keeps intracellular [glucose] low

How does the body regulate blood glucose in the fasted state using glucagon?

1. ↓ Plasma glucose

• Low glucose stimulates α cells in the pancreas

• At the same time, low glucose inhibits β cells, so insulin decreases (not enough plasma glucose to uptake)

2. α cells release glucagon (↑ glucagon) + ↑ plasma amino acids
   Glucagon’s main target is the liver.

3. Glucagon acts on the liver to raise blood glucose:

   • ↑ Glycogenolysis – liver breaks down glycogen → releases glucose

   • ↑ Gluconeogenesis – liver makes new glucose from:

     • Lactate

     • Pyruvate

     • Amino acids

   • During prolonged fasting:

     • Liver produces ketones from fatty acids

4. Other tissues help supply fuel:

   • Muscle, adipose, and other cells release:

     • Amino acids

     • Lactate/pyruvate

     • Fatty acids

   • These go to the liver to support gluconeogenesis and ketone production.

5. Result:

• Liver releases glucose into the blood → ↑ plasma glucose

• Brain and peripheral tissues now have fuel

• Rising glucose provides negative feedback, reducing further glucagon release

What are the pharmacologic properties of insulin?

• Protein metabolism

  • ↑ Transport amino acids into cells

  • ↑ Protein synthesis

  • Positive nitrogen Balance

• Diabetes - low insulin → ↑ aa, ↑ FFA (ketosis), ↓ protein synthesis, ↑ glycogenolysis, ↑ glucose

What is the fate of CHO?

• Absorbed as: Glucose primarily; also fructose and galactose

• Fed-state Metabolism:

  • Used immediately for energy through aerobic pathways (glycolysis and citric acid cycle)

  • Stored as glycogen in the liver and muscles (glycogenesis)

  • Excess converted to fat and strored in adipose tissue (lipogenesis)

• Fasted-state Metabolism:

  • Glycogen polymers are broken down (glycogenolysis) to glucose in the liver and kidneys or to G6P for use in glycolysis

What is the fate of proteins?

• Absorbed as: Amino acids, primarily plus some small peptides

• Fed-state Metabolism:

  • Most amino acids go to tissues for protein synthesis

  • If needed for energy, amino acids converted in liver to intermediates for aerobic metabolism (deamination)

  • Excess is converted to fat and stored in adipose tissue (lipogenesis)

• Fasted-state Metabolism:

  • Proteins broken down into amino acids

  • Amino acids deaminated in liver for ATP production or used to make glucose (gluconeogenesis)

What is the fate of fats?

• Absorbed as: Fatty acids, triglycerides, and cholesterol

• Fed-state Metabolism:

  • Stored as triglycerides primarily in the liver and adipose tissue (lipogenesis)

  • Cholesterol used for steroid synthesis or as a membrane component

  • Fatty acid used for lipoprotein and eicosanoid synthesis

• Fasted-state Metabolism:

  • Trigylcerides broken down into fatty acids and glycerol (lipolysis)

  • Fatty acids used for ATP production through aerobic pathways (beta oxidation)

How does metabolism work?

• All chemical reactions that take place in an organism

• Catabolism - breaking down molecules

• Anabolism - building complex molecules

• Kilocalories are measures of energy released from or stored in chemical bonds

• Primary source of energy for cellular reactions is adenosine triphosphate (ATP)

How do cells regulate their metabolic pathways?

1. Controlling enzyme concentrations

2. Producing modulators that change reaction rates

- Feedback inhibition

3. Using different enzymes to catalyze reversible reactions

4. Compartmentalizing enzymes within organelles

5. Maintaining optimum ratio of ATP to ADP

How do enzymes participate in feedback inhibition?

Control reversibility of metabolic reactions

What are the different types of work?

• Chemical work: Making and breaking of chemical bonds

• Transport work:

  • Moving ions, molecules, and larger particles

  • Useful for creating concentration gradients

• Mechanical Work

  • Moving organelles, changing cell shape, beating flagella and cillia

  • Contracting muscles

What are the two forms of energy?

• Kinetic Energy:

  • Energy of motion

  • Work involves movement

• Potential energy:

  • Stored energy

    • In concentration gradients and chemical bonds

  • Must be converted to kinetic energy to perform work

    • Transformation efficiency

What are the two laws of thermodynamics?

• First Law of thermodynamics: Total amount of energy in the universe is constant

• Second Law of thermodynamics: Processes move from state of order to randomness or disorder (entropy)

Chemical reactions

• Bioenergetics is the study of energy flow through biological systems

• Chemical reactions

  • Reactants become products

  • Reaction rate

• Free energy

• Activation energy

• Net free energy change of the reaction

  • Exergonic vs endergonic reactions

  • Coupled reactions (energy from 1st reaction can be used in the second)

• Reversible vs irreversible reactions

Enzymes

• Speed up the rate of chemical reactions

  • Catalysts

  • Reactants are called substrates

• Mostly proteins

• Isozymes

  • Catalyze same reaction, but under different conditions

  • Diagnostic enzymes (act differently in each environment)

• May be activated, inactivated, or modulated

  • Coenzymes → (e.g., vitamins)

  • Chemical modulators → temp and pH

• Enzymes lower the activation energy of reactions

What are the categories of enzymatic reactions?

• Oxidation-reduction reactions

• Hydrolysis-dehydration reactions

• Addition-subtraction-exchange reactions

• Ligation reactions

How is heat production, gain, and loss balanced?

• By body temperature!

• Humans are homothermic temperature regulated within narrow range

• Heat input = heat output

• Heat input

  • Internal heat production

  • External heat input (radiation and conduction)

• Heat output

  • Radiant heat loss

  • Conductive heat loss (can touch temp)

  • Convective heat loss (feel change in temp)

  • Evaporative heat loss (sweating/cooled)

How does the body maintain heat balance to regulate body temperature?

• External heat input + internal heat production = heat loss

• Heat Gain:

  • External heat input

    • From the environment via radiation and conduction

  • Internal heat production

    • From metabolism (“waste heat”)

    • From muscle contraction

      • Shivering thermogenesis (in cold)

      • Nonshivering thermogenesis

      • Above are regulated processes for temp homeostasis

• Heat Loss:

  • Radiation

  • Conduction

  • Convection

  • Evaporation

When you’re cold:

• Heat production ↑ (shivering, metabolism)

• Heat loss ↓

When you’re hot:

• Heat loss ↑ (sweating, vasodilation)

• Heat production ↓

What are the hypothalamic responses to increased vs decreased body temperature?

Explain how temperature is regulated through homeostasis.

How can body’s thermostat be reset?

• Physiological regulation

  • Circadian rhythm, menstrual cycle variations, postmenopausal hot flashes, fever

  • Fever is immune response to pyrogens

• Pathological conditions

  • Hyperthermia

    • Heat exhaustion

    • Heat stroke

    • Malignant hyperthermia

  • Hypothermia