Lecture 3 (1/23): Cellular Biology Energetics

Hypothalamic Centers

Feeding center

Satiety center

Feeding center

tonically active

Satiety center

inhibts feeding center

Glucostats Theory

glucose uptake causes the satiety center to send inhibitory signals to the hunger center and thus suppresses the appetite

Lipostatic Theory

Positive fat increases, leptin released, sends a signal to the brains to decrease energy store.

Peptides the Increase Food Intake

Ghrelin

NPY and Aguoti-related protein (AGPR)

Orexins (hyocretins)

Peptides that Decrease Food Intake

CCK

Glucagon-like peptide-1

Leptin

Corticotropin-releasing hormone (CRH)

alpha- Melanocyte-stimulating hormone (alpha-MSH)

CART (cocaine-and-amphetamine-regulated transcript) and POMC (pro-opiomelanocortin)

Ghrelin

Stomach

NPY and Agouti-related protein (AgRP)

Co-expressed in hypothalamus

Orexins

Hypothalamus

CCK

small, intestine, neurons

Glucagon-like-peptide-1 (GLP-1)

intestines

Leptin

Adipose cells

Corticotropin-releasing hormone (CRH)

Hypothalamus

alpha- Melanocyte stimulating hormone (alpha-MSH)

Hypothalamus

CART (cocaine-and-amphetamine-regulated transcript) and POMC (pro-opiomelanocortin)

Co-expressed in hypothalamus

First Law of Thermodynamics

Conservation of Energy

Energy Intake Equals

Diet

Energy output equals

Work+Heat

Work

Transport across membranes

Mechanical movement

Chemical- synthesis for growth and maintenance, energy storage of ATP and Chemical bonds

Energy Intake

Food Energy

Energy of Absorption

Digestive Waste

Fat

9

Carbohydrates

4

Fats

4

Energy Output

Indirect Calorimetry

Basl Metabolic Rate

Activity Level

Thermic Effect of Eating

Indirect Calorimetry

Oxygen Consumption

Carbon Dioxide Production

Respiratory Quotient

Metabolic Rate

Respiratory Quotient

1 for CHO

0.8 for Protein

0.7 for Fat

6 kcal/L O2

Products of Anaerobic Metabolism

0 NADH, 2 ATP

Products of Aerobic Metabolism TOTAL

6 H20, 20-32 ATP, 6CO2

Products of Aerobic Metabolism AFTER ETC

26-28 ATP

Lipid Anabolism: Step 1

Bile salts help break down dietary fats into components that can be absorbed

Lipid Anabolism: Step 2

Intestinal epithelial cells assemble absorbed cholesterol, lipoproteins, and lipid complexes into chylomicrons.

Lipid Anabolism: Step 3

Chylomicrons are transported to the blood via the lymphatic vessels

Lipid Anabolism: Step 4

Lipoprotein lipase converts triglycerides into free fatty acids and glycerol

Lipid Anabolism: Step 5

Adipose cells reassemble free fatty acids and glycerol into triglycerides for storage. Other cells use free fatty acids for enegy production.

Lipid Anabolism: Step 6

Chylomicron remnants and HDL-C enter the liver for further processing, creating lipoprotein complexes such as LDL and VLDL. Some of the cholesterol is recycled in new bile salts.

Lipid Anabolism: Step 7

LDL-C is transported via the blood to most of the cells, where the cholesterol is used for synthesis.

Lipid Catabolism: Step 1

Lipases digest triglycerides into glycerol and 3 fatty acids

Lipid Catabolism: Step 2

Glycerol becomes a glycolysis substrate

Lipid Catabolism: Step 3

Beta-oxidation chops 2-carbon acyl units off the fatty acid

Lipid Catabolism: Step 4

Acyl units become acetyl CoA and can be used in the citric acid cycle.

Deamination: Step 1

Removal of the amino group from an amino acid create ammonia and an organic acid.

Deamination: Step 2

Ammonia is toxic and must be converted to urea

Fed State

Energy absorbed and stored

Anabolism

Fasted State

Energy Used

Catabolism

Glucagon

alpha cells

Insulin

Beta cells

Somatostatin

delta cells

Pancreatic Polypeptide

F cells

Blood flow

from Beta cells to a and delta cells

Homrones of Glycemic Control

Glucagon

Insulin

Somatostatin

Epinephrine

Cortisol

GLP-1

Leptin

Source, Target Tissue, Action: Glucagon

a cells

Liver (adipose, skeletal muscle)

Promotes glycogenolysis and gluconeogenesis in liver

Source, Target Tissue, Action: Insulin

Beta cells

Liver (adipose, skeletal muscles)

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

Source, Target Tissue, Action: Somatostatin

delta cell, GI tract, hypothalamus

Other islet cells, GI tract, brains and pituitary gland

Lower release of insulin and glucagon, lower GI tract motility and lower growth hormone secretion

Epinephrine

Adrenal medulla

Many

Promotes glycogenolysis in lover., Lipolytic via hormone-sen. lipase

Cortisol

Adrenal cortex

ManyAntagonized insulin action

GLP-1

Illeum

Pancrease, stomach, brain, heart

Increase beta cell mass and insulin secretion. delays gastic emptying, food intake and glucagon secretion

Leptin

Adipocytes

CNS (basomedial hypothalamus)

Signals adequacy of energy stores, decreased food intake.

Glycogenesis

The process of synthesizing glycogen

Glycogenolysis

The process of breaking down glycogen to release glucose.

Gluconeogenesis

The process of synthesizing glucose

Glycolysis

the process of utilizing glucose metabolically

Fed State: Insulin vs Glucagon

Insulin dominates

Fasted State: Insulin vs Glucagon

Glucagon Dominates

Fasted State: Adipose and Resting Skeletal Muscle

The absence of insulin, there are not GLUT 4 transporters in the memebrane.

Fed State: Adipose and Resting Skeletal Muscle

Insulin signals the cell to insert GLUT 4 transporters into the membrane, allowing glucose to enter cell.

Fasted State: Liver Heptatocytes

The hepatocytes make glucose and trasnports it out into the blood, using GLUT 2 transporters

Fed State: Liver Heptatocytes

the glucose concentration gradient reverses and glucose enter the hepatocyte.

Pharmacological Properties of Insulin

Protein Metabolism

• Increase transport of amino acid into cells

• protein synthesis

• Positive nitrogen balance

Fed- State Metabolism: Carbohydrates

Used immediately for energy through aerobic pathways

used for lipoprotein synthesis in liver

Stored as glycogen in lover and muscle

Excess converted to fat and stored in adipose tissue

Fed- State Metabolism: Proteins

Most amino acids go to tissues for protein synthesis

If needed for energy, amino acids converted in lover to intermediates for aerobic metabolism,

Fed- State Metabolism: Fats

Stored as triglycerides primarily in the liver and adipose tissue

Cholesterol used for steroid synthesis or as a membrane component

Fatty acids used for lipoprotein and eicosanoid synthesis

Fasted-state Metabolism: Carbohydrates

Glycogen polymers broken down to glucose in lover and kidney or to glucose 6-phospoahe for use in glycolysis

Fasted-state Metabolism: Proteins

Proteins broken down into amino acid

Aminoa cids deaminated in liver for ATP production or used to make glucose

Fasted-state Metabolism: Fats

Triglycerides broken down into fatty acids and glycerol

Fatty acids used for ATP production through aerobic pathways

How cells regulate their metabolic pathways

1. controlling enzyme concentrations

2. Producing modulator that change reaction rates

3. Using different enzymes to catalyze reversible reactions

4. Compartmentalizing enzymes within organelles

5. Maintain optimim ration of ATP to ADP

Chemical work

making and breaking of chemicla bonds

Transport Work

Moving ions, molecules, and larger particle. Useful for creating concentration gradients

Mechanical work

Moving organelles, changing cell shape, beating flagella and cilia

Contracting muscles

Kinetic energy

energy of motion

Potential energy

stored energy in concentration gradients and chemical bonds

First Law of Thermodynamic

Energy is conserved

Second Law of Thermodynamics

the total entropy (disorder) of an isolated system can never decrease over time and is always increasing in spontaneous

Chemical Reactiosn

Net free energy change of the reaction

Combination

A+B—> C

Decomposition

C—> A+B

Single Displacement

L+MX—→ LX+M

Double Displacement

LX+MY—→ LY+MX

Activation energy

the push needed to start a reaction

Exergonic Reactions

Release energy because the products have less energy than the reactants

Endergonic Reactions

trap some activation energy in the products, which then ahve more free energy than the reactants

Enzymes

Speed up the rate of chemcial reactions

Mostly proteins

Isozymes

May be activated, inactivated, or modulated

Enzymes lower the activation energy of reactions

Acid phosphatase

Prostate cancer

Alkaline phospatase

disease of bone or liver

Amylase

Pancreatic disease

Creatine kinase

Myocardial infarction, muscle disease

Lactate dehydrogenase (DH)

Tissue damage to hear, liver, skeletal muscle, red blood cells.

Oxidation-reduction

add or subtract electrons

Hydrolysis-dehydration

add or subtract a water molecule