Principles of Cell and Systemic Physiology

Dr. DeBello, Fall 2024, Lectures 2-3

The Plasma Membrane

• A thin phospholipid bilayer studded with membrane proteins enclosing each cell

• Confer selective permeability to ions, glucose, and other molecules

Membrane Proteins

• Imbedded into the plasma membrane

• Channels and carries to transport molecules and ions into and out of the cell

• Receptors to signal responses

• Form adhesions and junctions

The Nucleus

• Membrane bound organelle containing the genetic material

• Is the sight of replication and transcription (produces mRNAs that are exported to the cytoplasm)

The Cytoplasm

• Portion of the cells interior not occupied by the nucleus

• Contains cytosol, organelles, and the cytoskeleton

The Cytosol

• Semiliquid portion of the cytoplasm

• Enzymatic regulation of intermediate metabolism

• Ribosomal protein synthesis

• Storage of fat and glycogen

Ribosomes

• Site of protein synthesis (translation)

• Found studded on the endoplasmic reticulum (ER) or free in the cytosol

Organelles

• Membrane-enclosed structures that carry out specific functions

• Five main types similar in all cells

  • Endoplasmic Reticulum

  • Golgi Complex

  • Lysosomes

  • Peroxisomes

  • Mitochondria

Endoplasmic Reticulum (organelle)

• Continuous fluid filled network of membranous tubules

• Rough ER: membrane covered with ribosomes

• Smooth ER: membrane lacking ribosomes

Golgi Complex (organelle)

• Processes raw material into finished products

• Directs products to their destination

Lysosomes (organelle)

• Membrane-enclosed sacs containing hydrolytic enzymes

• Digest debris by fusing with intracellular vesicles often derived from endocytosis

Peroxisomes (organelle)

• Membrane-enclosed sacs containing oxidative enzymes which act to remove hydrogen from toxic molecules

• Detoxify free radicals

Mitochondria (organelle)

• Responsible for aerobic metabolism and the production of cellular energy (ATP)

• Produces ATP from glucose or fatty acids (amino acids in extreme cases)

Aerobic Metabolism (mitochondria)

• Glycolysis: occurs in cytosol, no oxygen required, yields 2 ATP

• TCA Cycle: occurs in mitochondria, no oxygen required, yields 2 ATP

• Electron Transport: occurs in mitochondria, oxygen required, yields 28-32 ATP

How do the endoplasmic reticulum and Golgi complex work together?

• The ER and Golgi complex use vesicle-based systems, budding and fusion, to sort new proteins to either the plasma membrane, outside the cell (soluble proteins released by exocytosis), or lysosomes

• Proteins made in the ER are never part of the cytoplasm, they are contained in the lumen

  • Once proteins are synthesized on ribosomes, they stay inside the endomembrane system

Where do organelles (besides lysosomes) and the cytoplasm get their proteins?

• The mitochondria makes a few proteins from their own mini genome and transcription/ translation apparatus

• Other organelles and the cytoplasm get their proteins from free ribosomes

The Cytoskeleton

• Protein network for structural support, transport, and cellular movement

• The major components

  • Microtubules

  • Microfilaments

  • Intermediate Filaments

Microtubules (cytoskeleton)

• Dynamic polymers of tubulin

• Form highways for movement of transport vesicles via kinesin and dynein motor proteins, and cilia and flagella for generating movements

Microfilaments (cytoskeleton)

• Dynamic polymers of actin

• In association with myosin (motor protein), they produce cellular contraction

Intermediate Filaments (cytoskeleton)

• Longer proteins produced by an array of different genes

• Provide support for components subject to mechanical stress

What does complex multicellular life require?

• Many different types of cells specialized for different tasks

• Differential gene expression is the proximate cause

  • All cell types contain the same DNA, but express unique subsets for any given cell type

Levels of Organization

1. Cell

2. Tissue

3. Organ

4. Organ System

5. Organism

Tissue (levels of organization)

• Aggregate of cells and extracellular material

• Four types

  • Muscle: contraction

  • Nervous: electrochemical signals

  • Connective: structural support

  • Epithelial: exchange

    • Exocrine: external secretion

    • Endocrine: internal secretion

Organ (levels of organization)

• Two or more primary tissues organized to perform a function

Organ System (levels of organization)

• Organs working together to perform a function to maintain homeostasis

Homeostasis

• Dynamic maintenance of a stable internal (extracellular) environment within the organism

• Essential to the survival of each cell

• Requires continual exchange of material between the inter and extracellular spaces

• Each organ system contributes by counteracting changes of internal environments

Intrinsic (homeostasis)

• Local control system built into an organ

Extrinsic (homeostasis)

• External control system outside of an organ permitting coordinated regulation of several organs

Negative Feedback (homeostasis)

• Change in a controlled variable triggers a response that opposes the change- return to the ‘normal’ state, maintain homeostasis

  • Sensor, set point, integrator, effector

Sensor (negative feedback)

• Mechanism to detect the controlled variable

• Constant

Set Point (negative feedback)

• The desired value of the variable

Integrator (negative feedback)

• Compares the sensor’s input with the set point

• Notices the direction and magnitude of change

• Activates or inhibits the effector

Effector (negative feedback)

• Adjusts the value of the controlled variable

• Activated or inhibited by the integrator

Positive Feedback (homeostasis)

• Reinforces the change in a controlled variable

  • Occurs very rarely

Extracellular Chemical Messengers

• Specific ligand-receptor interactions

• Ligand typically activates the receptor

• Cellular response depends on the molecular identity of the receptor

• Three types: hormonal, paracrine, synpatic

Hormonal (extracellular chemical messengers)

• Releases signal into blood stream, which goes body wide

• Exposed to all cells but only activates those with the receptor

Paracrine (extracellular chemical messengers)

• Cell releases signaling molecules which are detected by cells around it which have the receptor

• Cells in the same tissue

• About 10-100 microns

Synaptic (extracellular chemical messengers)

• Signal released into the extracellular space and is detected by the postsynaptic cell

• About 1 micron

• Detected at one part of one cell

Extracellular Chemical Messenger Receptors

• Specific ligand-receptor interactions, typically the ligand activates the receptors

• Cellular response depends on the molecular identity of the receptor

• Four types: nuclear, GPCRs, enzyme-linked, ionotropic

Nuclear Receptor (extracellular chemical messenger receptor)

• Intracellular

• Chemical messenger/ molecule diffuses through the plasma membrane and binds to a nuclear receptor protein

• The activated complex moves into the nucleus and binds to the regulatory region of the target gene and activates transcription

GPCR (extracellular chemical messenger receptor)

• Chemical messenger binds to the cell surface receptor, which activates a G-protein cascade, leading to a sequence of phosphorylation events that alter the shape and function of preexisting proteins and bring about a cellular response

Enzyme-Linked Receptor (extracellular chemical messenger receptor)

• Cell surface receptors that bind their ligand and initiate an enzymatic cascade

Inotropic Receptor (extracellular chemical messenger receptor)

• Chemical messenger, a neurotransmitter, binds the receptor and opens the ion channel, allowing ions to flow down their electrochemical gradient