Dr. William R. Law

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PHYB 301Human Physiology
Basic cell physiology, membranes, and the
membrane potential
Dr. William R. Law Room 203A, CMW 6-7622 wrlaw_at_uic
.edu
http//www.uic.edu
/wrlaw
Office hours 630-830 AM 1230-130 PM
Office hours 630-830 AM 1230-130 PM
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Why study pathophysiology?
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Homeostasis the foundation of Physiology

• When things go right a balance of interactive
  and varied
• functions at all levels of organization

• The body is considered from the perspective of
  the interactions of different organ systems
• Organs are considered from the vantage of the
  interactions of different cell types.
• Cells are viewed from the perspective of the
  interactions of different structures and
  organelles.
• Structures/organelles from the perspective of
  interactions of different molecules

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Homeostasis the foundation of Physiology
When things go wrong the balance has been
disrupted, or a new, deleterious balance has been
instituted. PATHOPHYSIOLOGY

• Teleological approach molecules, organelles,
  celles, organs, etc, fulfill a bodily need.
• Mechanistic approach molecules, organelles,
  cells, organs, etc, just do.

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Homeostasis the foundation of Physiology
Homeostasis occurs through key regulatory
paradigms to achieve steady-state conditions

• Feedback the effect influences the cause
• thermostat
• Hierarchical communication there is a command
  structure controlling an outcome.
• Hypothalamus-pituitary-adrenal axis
• Adaptation the steady-state is changed to
  accommodate a new situation
• Altitude

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Why cellular physiology?The cell is the smallest
unit capable of carrying out the processes
associated with life.

• Classical Properties of Living Organisms
• Reproduction
• Nutrition
• Respiration
• Excretion
• Irritability/respond
• Movement
• Growth

• How cells fulfill these criteria of Living
  Organisms
• Cell replication
• Nutrition
• Respiration
• Excretion
• Respond to environment
• Movement within and externally
• Grow in number and size

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Organization of the cell

• Membranes
• Plasma membrane encompasses the functional cell
  unit
• Membranes segregate most other individual
  components of the cell
• Nucleus
• Organelles
• Cytoplasm - suspension of fluid with various
  cellular elements

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Double membrane
Cristae
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Double membrane
Cristae
Matrix
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Mitochondria Cellular Power Plant

• Unique Characteristics
• Contains its own DNA (maternal lineage only)
• Double membrane
• The inner memrane is heavily folded into
  "cristae"
• The gel-like fluid "matrix" contains enzymes for
  production of adenosine triphosphate (ATP)
• Energy conversion
• C-H bonds of substrate (food) is converted to
  high energy phosphate bonds through the citric
  acid cycle (also called the Kreb or tricarboxylic
  acid cycle).
• Hydrogen atoms carried by nicotinamide adenine
  dinucleotide (NAD) and flavine adenine
  dinucleotide (FAD)
• importance of niacin and riboflavin
• Electrons carried through a very ordered series
  of reactions to incoporate energy into usable
  form (ATP)

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GDP
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Mitochondria Cellular Power Plant

• Unique Characteristics
• Contains its own DNA (maternal lineage only)
• Double membrane
• The inner memrane is heavily folded into
  "cristae"
• The gel-like fluid "matrix" contains enzymes for
  production of adenosine triphosphate (ATP)
• Energy conversion
• C-H bonds of substrate (food) is converted to
  high energy phosphate bonds through the citric
  acid cycle (also called the Kreb or tricarboxylic
  acid cycle).
• Hydrogen atoms carried by nicotinamide adeninje
  dinucleotide (NAD) and flavine adenine
  dinucleotide (FAD)
• importance of niacin and riboflavin
• Electrons carried through a very oerdered series
  of reactions to incoporate energy into usable
  form (ATP)

• Oxygen is the final electron acceptor combines
  with H to form water
• Carbon combines with oxygen to form CO2

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Organization of the cell

• Membranes Structurally define cells, nucleus,
  and organelles.
• Phospholipids

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Phsopholipids are amphipathic

• Phospholipids are polar, having hydrophobic
  "tails" made of lipids, and hydrophilc "head"
  groups
• Phosphatidylcholine head is choline (lecithins)

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Phospholipids are amphipathic

• Phospholipids are polar, having hydrophobic
  "tails" made of lipids, and hydrophilc "head"
  groups
• Phosphatidylcholine head is choline (lecithins)

• Phosphatidylethanolamine head is ethanolamine
• Phosphatidylinositol wellyou get the idea
• The hydrophobic "tail" is composed of varying
  phospholipids, a fatty acid esterified to
  glycerol or (serine sphingomyelin)
• Because of this polar nature, phospholipids
  self-assemble in aqueous solutions to form
  bilayers.

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micelle
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Organization of the cell

• Membranes Structurally define cells, nucleus,
  and organelles.

• Phospholipids- primary building block of the
  membrane
• Fluid mobile
• Individual phospholipids remain in a singel
  monolayer
• Provide some substrate for cellular signalling
• Cholesterol
• stiffens membranes
• Can move in any dimension through membrane
• Glycolipids lipid/sugar moiety
• Proteins
• Glycoprotein protein/sugar moiety

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DNA
RNA
Protein
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RNA

• Messenger RNA (mRNA) - long, single nucleotide
  strands that resemble half of a DNA molecule and
  carry the "message" containing instructions for
  protein synthesis from the DNA in the nucleus to
  the ribosomes in the cytoplasm.
• Transfer RNA (tRNA) - small, between 70 and 80
  nucleotides, cloverleaf-shaped molecules that
  transfer amino acid molecules to the mRNA.

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Protein synthesisinvolves two major phases

• Transcription - complementary mRNA is made at the
  DNA gene. Three-base sequences, or triplets, on
  the DNA specify a particular amino acid. The
  corresponding three-base sequences on mRNA are
  called codons. The form is different, but the
  information is the same.
• Translation The mRNA is "decoded" to assemble
  proteins in a ribosome using tRNA. The language
  of nucleic acids (base sequence) is "translated"
  into the language of proteins (amino acid
  sequence). There are four basic steps
• Messanger RNA from the nucleus attaches to a
  ribosome in the cytoplasm.
• Transfer RNA transports an amino acid to the mRNA
  strand and recognizes a mRNA codon calling for
  its amino acid by binding its anticodon to the
  codon.
• The ribosome moves the mRNA strand along as each
  codon is read sequentially.
• As each amino acid is bound to the next by a
  peptide bond, its tRNA is released. The
  polypeptide chain is released when the
  termination (stop) codon is read.

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Endoplasmic Reticulum (ER)Cellular manufacturing
facilities

• Major site of protein synthesis
• ribosomes begin the polypeptide synthesis process
  with a segment that binds to a signal-recognition
  protein (SRP) in the cytoplasm.
• SRP associates with a transmembrane receptor, or
  docking protein, on the rough ER. NOTE the
  SRP inhibits peptide synthesis until it can
  dock.
• Synthesis and translocation of the polypeptide
  into the ER occur simultaneously.

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Endoplasmic Reticulum (ER)Cellular manufacturing
facilities

• Major site of protein synthesis
• ribosomes begin the polypeptide synthesis process
  with a segment that binds to a signal-recognition
  protein (SRP) in the cytoplasm.
• SRP associates with a transmembrane receptor, or
  docking protein, on the rough ER. NOTE the
  SRP inhibits peptide synthesis until it can
  dock.
• Synthesis and translocation of the polypeptide
  into the ER occur simultaneously.

• Secretory proteins
• translocated freely into interior of the ER
• Move to "smooth" ER secrion for encapsulation
• Vesicle "pinched off" for secretion, or further
  processing at Golgi complex

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Endoplasmic Reticulum (ER)Cellular manufacturing
facilities

• Major site of protein synthesis
• ribosomes begin the polypeptide synthesis process
  with a segment that binds to a signal-recognition
  protein (SRP) in the cytoplasm.
• SRP associates with a transmembrane receptor, or
  docking protein, on the rough ER. NOTE the
  SRP inhibits peptide synthesis until it can
  dock.
• Synthesis and translocation of the polypeptide
  into the ER occur simultaneously.
• Secretory proteins
• translocated freely into interior of the ER
• Move to "smooth" ER secrion for encapsulation
• Vesicle "pinched off" for secretion, or further
  processing at Golgi complex

• Transmembrane proteins
• Translated into the ER membrane
• Membrane and protein is later incorporated into
  plasma membrane or membrane of other organelles

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Endoplasmic Reticulum (ER)Cellular manufacturing
facilities

• Major site of protein synthesis
• ribosomes begin the polypeptide synthesis process
  with a segment that binds to a signal-recognition
  protein (SRP) in the cytoplasm.
• SRP associates with a transmembrane receptor, or
  docking protein, on the rough ER. NOTE the
  SRP inhibits peptide synthesis until it can
  dock.
• Synthesis and translocation of the polypeptide
  into the ER occur simultaneously.

• Other functions "smooth" ER contains enzymes for
• Lipid synthesis lipid and steroidal hormone
  synthesis
• Detoxifying endogenous and exogenous toxic
  substances (esp. liver)
• Calcium storage (muscle sarcoplasmic reticulum)

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Golgi Complex The devil is in the details
Transport vesicles from smooth ER
Fuse with golgi stack, and proteins undergo
refinement
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Golgi ComplexCellular refining facilities

• Post-translational Modification
• Glycosylation (oligosaccharide )
• Disulfide bonds
• Folding
• Quaternary structure
• Sorting and directing

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Vesicular TransportSorting and
Directing(Example proteins for secretion)

• Directed binding of proteins to specific markers
• Sorting signal on the protein to be secreted
• Recognition marker on golgi-binds the sorting
  signal

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Vesicular TransportSorting and
Directing(Example proteins for secretion)

• Directed binding of proteins to specific markers
• Sorting signal on the protein to be secreted
• Recognition marker on golgi-binds the sorting
  signal

• Triskelions (clathrin) or adaptins in cytosol
  form a "coating" that also causes bulging to form
  the vesicle.
• Coating may (or not) shed, exposing the V-snare

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V-snare docks at T-snare on target
membrane Protein released beyond the membrane
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Triskelion (clathrin) self-assembly
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LysosomesCellular cleanup crew

• Membrane-enclosed sacs of hydrolytic enzymes
• Remove cellular debris
• Destroy invading pathogens

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Vaults Ribonucleoprotein complexes that contain
untranslated RNA. Function speculated storage,
transport, or removal? Elevated in multi-drug
resistance in cancers.
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Cytosol(cytoplasm and friends)

• Ribosomal protein synthesis
• Intermediate metabolism and storage degradation,
  synthesis, or transformation of small organic
  molecules for fuel.
• Metabolism
• Glycolysis - breakdown of simple sugars (esp.
  glucose) for oxidative metabolism. Yields small
  amount of energy.
• Process fatty and amino acids for entry into TCA
  cycle
• Storage
• Fat droplets (esp adipose cells)
• Glycogen
• Ultrastructure - the cytoskeleton
• Microtubules at 22 nm, the largest of the
  cytoskeletal structures composed of tubulin
• Architecture needed to maintain asymetry (Ex.
  Axons) or act as scaffolding during development
• Motion
• Transport of materials (vesicles, etc.)
• Movement
• Mitosis

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Cytosol(cytoplasm and friends)

• Ribosomal protein synthesis
• Intermediate metabolism and storage degradation,
  synthesis, or transformation of small organic
  molecules for fuel.
• Metabolism
• Glycolysis - breakdown of simple sugars (esp.
  glucose) for oxidative metabolism. Yields small
  amount of energy.
• Process fatty and amino acids for entry into TCA
  cycle
• Storage
• Fat droplets (esp adipose cells)
• Glycogen
• Ultrastructure - the cytoskeleton
• Microtubules at 22 nm, the largest of the
  cytoskeletal structures composed of tubulin
• Architecture needed to maintain asymetry (Ex.
  Axons) or act as scaffolding during development
• Motion via dynein and kinesin

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Cytosol(cytoplasm and friends)

• Ribosomal protein synthesis
• Intermediate metabolism and storage degradation,
  synthesis, or transformation of small organic
  molecules for fuel.
• Ultrastructure - the cytoskeleton
• Microtubules at 22 nm, the largest of the
  cytoskeletal structures composed of tubulin

• Microfilaments at 6 nm, the smallest visible
  with standard EM composed of actin (G-form),
  which forms twisted strands (F-form).
• Architechture cell section stiffeners
• Microvilli increased surface areas in repeating
  pattern
• Stress fibers interconnect membrane sections
  forming support
• Movement
• Commonly with myosin molecules
• Myofilaments
• Transport
• Amoeboid motion cyclic assembly/dissembly of
  actin from sol to gel state

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Cytosol(cytoplasm and friends)

• Ribosomal protein synthesis
• Intermediate metabolism and storage degradation,
  synthesis, or transformation of small organic
  molecules for fuel.
• Ultrastructure - the cytoskeleton
• Microtubules at 22 nm, the largest of the
  cytoskeletal structures composed of tubulin
• Microfilaments at 6 nm, the smallest visible
  with standard EM composed of actin (G-form),
  which forms twisted strands (F-form).

• Intermediate filaments stable protein strands,
  7-10 nm Provide a stable framework within the
  cell.

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"free" ribosomes
ER
Plasma membrane
mitochondrion
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