1. introduction to physiology.membrane physiology

Welcome to the Physiology Course! Course Director: Motoc Daniela MD, PhD motocdana2005@yahoo.com

AP Biology

Course Requirements/Recommendations:

1)   Attend lectures

2)   Readings

a)   Class handouts – required readings

b)  Textbooks

i)   Medical Physiology by Boron and Boulpaep

ii)   Physiology by Berne and Levy

iii)   Textbook of Medical Physiology by Guyton iv)   Review of Medical Physiology (Lange series) by Ganong

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PHYSIOLOGY BOOKS

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Human Physiology

•  Study of how the human body functions. •  Pathophysiology:

– How physiological processes are altered in disease or injury.

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Goal of this course: 1) To understand cellular physiology 2) To understand how each organ system works to maintain

the composition, volume and pressure of the extracellular fluid.

3) Understanding from the whole human body level to the molecular level

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What is Physiology? Focuses on homeostasis, the maintenance of important properties of living organisms in a narrow range in the face of significant environmental fluctuations Examples of properties

blood pressure ionic composition of blood osmolarity of blood oxygen and carbon dioxide content of blood acid-base balance of blood glucose concentration of blood body temperature

Goals are to identify the processes that control and regulate the important properties of living systems

sensors – afferent pathways integrating centers - set points effectors – efferent pathways

How do these systems respond to perturbations in order to return to normal?

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Physiology is Different Than Histology or Anatomy

Concepts vs Memorization like physics there are things to memorize but it is the concepts that are essential you must put in the intellectual effort to understand the concepts you must think about the ideas to become comfortable with them do not expect that you will learn physiology by cramming for exams

Dynamic vs Static subject

new discoveries new insights so what you learn today may need to be revised in the future

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What is Physiology? Focuses on homeostasis, the maintenance of important parameters in living organisms in a narrow range (in the steady state) in the face of significant environmental fluctuations

normal range

elevated

decreased

Example: body temperature

Shivering

Sweating

Core Body Temperature Sensors

CNS Integrating Center

Sweat Ducts

Skeletal Muscle, Brown Fat

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Physiology is the Basis of Medicine many diseases cause organ dysfunction medicine

tries to correct dysfunction or minimize its effects trying to restore system towards normal homeostatic setpoint

need to understand physiological parameters that can be manipulated Example – Congestive Heart Failure (CHF)

leads to pump failure – inability to maintain adequate level of circulation need to know causes of failure some may be reversible others irreversible if irreversible what else can be done to maximize pumping minimize symptoms changes in blood volume, arterial or venous blood pressure at molecular level need to know potential targets that can be modulated

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Chemical Composition of the Body

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Elements

•  Four elements important to living organisms – Carbon (C) – Nitrogen (N) – Oxygen (O) – Hydrogen (H)

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Four main classes of organic molecules

•  Lipids •  Carbohydrates •  Proteins •  Nucleic Acids

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Lipids

•  GR: Lipos=Fat •  Diverse group of molecules. •  Insoluble in polar solvents (H20). •  Hydrophobic (nonpolar) •  Consist primarily of hydrocarbon chains and

rings.

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Lipids

•  Hydrocarbons •  Fatty acids •  Triglycerides •  Ketone Bodies •  Phospholipids •  Steroids •  Prostaglandins

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Carbohydrates

•  Organic molecules that contain carbon, hydrogen and oxygen.

•  CH20 •  General formula:

– CnH2nOn

•  -ose denotes a sugar molecule

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Carbohydrates

•  Supply energy – Glucose – Complex carbohydrates

•  Provide structural support – cellulose

•  Part of plasma membrane •  Monomer: monosaccarides

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Carbohydrates

•  Monosaccharide: the “simple sugars” – Pentoses (5-carbons):

•  Ribose: in RNA •  Deoxyribose: in DNA

– Hexoses (6-carbons):structural isomers •  Glucose, fructose and galactose •  Characteristics

–  Soluable –  Sweet –  Alcoholic fermentation

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Carbohydrates

•  Disaccharide: – 2 monosaccharides joined covalently.

• Sucrose – Glucose and fructose

• Maltose – Glucose and glucose

• Lactose – Glucose and galactose

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Carbohydrates

•  Polysaccharides: – Many monosaccharides joined covalently. – General formula: (C6H10O5)n

– Characteristics: • Devoid of taste • Do not form solutions •  Iodine test

– Iodine +starch+blue

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Polysaccarides

•  Kinds: – Starch

•  Glucose subunits •  branched

– Dextrins – Glycogen (animal starch)

•  Glucose subunits •  Branched

– Cellulose •  Glucose subunits •  Long, unbranched chains

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Proteins

•  General Information: – GR: proteios=first rank – ~50% of the organic material of the

body – Functions

• Structural: – Cell structures, CTs

• Functional: – Enzymes, hormones, Hb, etc!

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Proteins

•  Protein Structure – Large molecules (polymers)

composed of amino acid sub-units (monomers).

– Amino Acid structure • amino group (NH2) •  carboxylic acid group (COOH) • Radical group (R): functional group • H

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Proteins

•  20 different standard amino acids. – Based on the properties of the

functional group – E.g.:

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Proteins

•  Dipeptide: 2 amino acids •  Tripeptide: 3 amino acids •  Polypeptide: many amino acids

– Number of amino acids varies – Up to 100 aa

•  Protein – Over 100aa – Great variety!

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Conjugated proteins

•  Protein combined with another type of molecule

•  Glycoproteins: carbohydrate with protein – Membranes, hormone

•  Lipoproteins: Lipid and protein – Membranes, blood plasma

•  Hemoproteins: iron and protein – Hemoglobin, cytochromes

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Nucleic Acids

•  Include the macromolecules: –  DNA: deoxyribonucleic acid –  RNA: ribonucleic acid

•  Involved in heredity and genetic regulation •  Are polymers:

–  Monomeric subunit:nucleotides –  Bonded together in a dehydration synthesis

reaction

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Nucleic Acids

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Nucleotides

•  Structure of a nucleotide: 3 subunits – Pentose sugar – Phosphate group – Nitrogenous base

•  Purines: two rings – Guanine –  Adenine

•  Pyrimidines: one ring – Cytosine –  Thymine – Uricil

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Nucleotide Structure

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DNA

•  Huge molecules with simple structure •  Big time data storage! •  Structure

– Nucleotides •  Pentose sugar: Deoxyribose •  Bases:

–  Purines: G and A –  Pyrimidines: C and T

– Form double-stranded helix

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DNA

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RNA

•  Means by which DNA directs cellular activities •  Structure

–  Pentose sugar: ribose –  Bases: uracil (not thymine) –  Single stranded

•  Three main types –  Messenger RNA (mRNA) –  Transfer RNA (tRNA) –  Ribosomal RNA (rRNA)

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DNA vs RNA

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Cell

•  Basic living unit of structure & function of the body. –  > 100 trillion cells in body. –  very small (10-5 m in diameter). –  highly organized. –  variety of shapes & sizes. –  each type of cells has a special function.

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Primary Tissues

•  4 Different Primary Tissues: – Muscle – Nervous – Epithelial – Connective

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Muscle Tissue

•  Specialized for contraction. •  3 Types of Muscle Tissue:

– Skeletal – Cardiac – Smooth

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Epithelial Tissue

•  Types of Epithelial Tissue: – Cells that form membranes:

• Squamous • Columnar • Cuboidal

– Exocrine glands – Endocrine glands

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Connective Tissue

•  Large amounts of extracellular (ECF) material in the spaces between connective tissue cells.

•  4 Types of Connective Tissue: – Connective tissue proper – Cartilage – Bone – Blood

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Connective Tissue Proper

•  Loose connective tissue: – Scattered collagen and tissue fluid.

•  Dermis of skin

•  Dense fibrous connective tissue: – Regular arranged.

•  Collagen oriented in same direction. –  Tendons

–  Irregularly arranged. •  Resists forces applied in many directions.

– Capsules and sheaths

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Organs

•  Organs: – Composed of at least two primary

tissues. – Serve different functions of the organ.

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Systems

•  Organs that are located in different regions of the body and perform related functions.

•  Examples: – Skeletal system – Cardiovascular system – GI system

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Cell

•  All Cells share certain characteristics:

–  general cell structure & components. –  general mechanisms for changing nutrients to

Energy. –  deliver end products into their surrounding fluid. –  almost all have the ability to reproduce.

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Cell (continued)

•  Great diversity of function. –  Organ physiology derived from complex functions of

the cell. •  3 principal parts:

–  Plasma membrane. –  Cytoplasm and organelles. –  Nucleus.

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General Cell structure:

o  The cell has two major compartments: the nucleus & the cytoplasm. The cytoplasm contains the major cell organelles & a fluid called cytosol.

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General Cell Structure & Function

Function Structure Component Surrounds, holds cell together & gives its form; controls passage of materials into & out of cell

Membrane composed of double layer of phospholipids in which proteins are embedded

Cell membrane

Serves as matrix substance in which chemical reactions occur.

Fluid, jellylike substance b/w cell membrane & nucleus in which organelles are suspended

Cytoplasm

Supports nucleus & controls passage of materials b/w nucleus & cytoplasm

Produces ribosomal RNA for ribosomes

Contains genetic code that determines which proteins (including enzymes) will be manufactured by the cell

Double-layered membrane that surrounds nucleus, composed of protein & lipid molecules

Dense nonmembranous mass composed of protein & RNA molecules

Fibrous strands composed of protein & DNA

Nucleus: - Nuclear envelope

- Nucleolus

- Chromatin

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Cytoplasm and Organelles

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Cytoplasm, Organelles, Nucleoli (continued)

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Cytoplasm and Cytoskeleton

•  Cytoplasm: –  Jelly-like matrix within

the cell. –  Includes organelles and

cytosol. –  Highly organized

structure with microtubules and microfilaments that function as cytoskeleton.

•  Cytoskeleton: –  Actin and myosin

(microfilaments). –  Spindle apparatus

(microtubules).

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Cytoplasm

•  The aqueous content of a cell (fluid, jellylike substance), that lies beetwen cell membrane and nucleus in which organelles are suspended.

•  Serves as matrix substance in which chemical reactions occur.

•  ‘Cytosol’ is the term used to describe fluid portion of

the cytoplasm.

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Organelles •  Subcellular structures within the cytoplasm that perform specific

functions.

o  Mammalian cell showing organelles common to all cells and specialized structures (e.g., cilia) found only in some cells.

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Cytoplasmic Organelles: Structure & Function

Function Structure Component

Agranular (smooth) ER metabolizes nonpolar compounds & stores Ca2+ in striated muscle cells; granular (rough) ER assists in protein sysnthesis

System of interconnected membrane-forming canals & tubules

Endoplasmic reticulum

Synthesize proteins Granular particles composed of protein & RNA

Ribosomes

Synthesizes carbohydrates & packages molecules for secretion. Secretes lipids & glycoproteins

Cluster of flattened membranous sacs

Golgi complex

Release energy from food molecules & transform energy into usable ATP

Membranous sacs w folded inner partitions

Mitochondria

Digest foreign molecules & damaged organelles

Membranous sacs Lysosomes

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Function Structure Component

Contain enzymes that detoxify harmful molecules & break down hydrogen peroxide

Spherical membranous vesicles

Peroxisomes

Helps to organize spindle fibers & distribute chromosomes during mitosis

Nonmembranous mass of 2 rodlike centrioles

Centrosome

Store & release various substances within the cytoplasm

Membranous sacs Vacuoles

Support cytoplasm & fx as cytoskeleton, transport materials within the cytoplasm

Thin, hollow tubes Microfilaments & microtubules

Move particles along cell surface, or move the cell

Minute cytoplasmic projections that extend from the cell surface

Cilia & flagella

Cytoplasmic Organelles: Structure & Function (continued)

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Cell Nucleus

•  Is a large spheroid body. •  Largest of organelles. •  Contains the genetic material (DNA). •  Most cells have a single nucleus.

•  Enclosed by inner & outer membrane (nuclear envelope). –  Outer membrane is continuous w ER.

•  Nuclear pore complexes fuse inner & outer membranes together. –  Selective active transport of proteins & RNA.

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Cell Nucleus

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Cell Nucleus (continued)

•  Nucleoli: –  Dark areas within the nucleus, not surrounded by

membrane. –  Centers for production of ribosomes.

•  Chromatin: –  Threadlike material that makes up

chromosomes.

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Plasma membrane:

•  Surrounds, holds cell together and gives its form. •  10 nanometer thick. •  Not solid. •  Separates cell’s internal structures from

extracellular environment. •  Is selectively permeable, controls passage of

materials into and out of cell. •  Participates in intracellular communication.

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Plasma (Cell) Membrane

Composed of:

–  Double layer of phospholipids (hydrophobic/ hydrophilic parts).

–  Proteins span, or partially span the membrane.

–  Negatively charged carbohydrates attach to the outer surface.

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The Cell Membrane

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General composition of cell membrane

•  Proteins ……………………. 55% •  Lipids ……………………….. 41% - Phospholipids … 25%

- Cholesterol ……. 12% Lipids

- Glycolipids …….. 4%

•  Carbohydrates …………… 3%

AP Biology

Cell membrane phospholipids

•  Consists of:

a. Glycerol head that contains phosphate gp (polar & hydrophilic).

b. 2 fatty acid ‘tails’ (nonpolar & hydrophobic).

•  The hydrophobic parts restricts the passage of H20 & H20- soluble ions.

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Phospholipid bilayer

•  Phospholipids –  Are the most abundant lipid in the plasma

membrane –  Are amphipathic, containing both hydrophobic

and hydrophilic regions •  Scientists studying the plasma membrane

–  Reasoned that it must be a phospholipid bilayer

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Phospholipid bilayer (cross section)

Hydrophilic head Hydrophobic tail

WATER

WATER

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Phospholipids

Fatty acid

Phosphate

•  Fatty acid tails –  hydrophobic

•  Phosphate group head –  hydrophilic

•  Arranged as a bilayer

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Membrane fat composition varies •  Fat composition affects flexibility

–  membrane must be fluid & flexible –  % unsaturated fatty acids in phospholipids

•  keep membrane less viscous •  cold-adapted organisms, like winter wheat

–  increase % in autumn –  cholesterol in membrane

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The Fluidity of Membranes:

•  Phospholipids in the plasma membrane –  Can move within the bilayer

•  The type of hydrocarbon tails in phospholipids –  Affects the fluidity of the plasma membrane

•  The steroid cholesterol –  Has different effects on membrane fluidity at

different temperatures

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The fluidity of membranes

Lateral movement (~107 times per second)

Flip-flop (~ once per month)

Fluid Viscous

Unsaturated hydrocarbon tails with kinks

Saturated hydro- Carbon tails

(a) Movement of phospholipids

(b) Membrane fluidity

(c) Cholesterol within the animal cell membrane

Cholesterol

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The Permeability of the Lipid Bilayer

•  A cell must exchange materials with its surroundings, a process controlled by the plasma membrane

•  Membrane structure results in selective permeability –  Hydrophobic molecules

•  Are lipid soluble and can pass through the membrane rapidly

–  Hydrophilic molecules •  Do not cross the membrane rapidly

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More than lipids… •  In 1972, S.J. Singer & G. Nicolson proposed that

membrane proteins are inserted into the phospholipid bilayer

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A Mosaic of Membrane Proteins

•  A membrane –  Is a mosaic of different proteins embedded

in the fluid matrix of the lipid bilayer

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1. Integral proteins: / Internal or intrinsic proteins - span the membrane. - transport proteins. - provide structural channels or pores.

2. Peripheral proteins: / external or extrinsic proteins - embedded in one side (face) of the membrane. - carrier proteins. - bind w substances to be transported. - include hormone receptors and cell surface antigens.

Cell membrane proteins

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Membrane is a collage of proteins & other molecules embedded in the fluid matrix of the lipid bilayer

Extracellular fluid

Cholesterol

Cytoplasm

Glycolipid

Transmembrane proteins

Filaments of cytoskeleton

Peripheral protein

Glycoprotein

Phospholipids

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The detailed structure of an animal cell’s plasma membrane, in cross section

Glycoprotein

Carbohydrate

Microfilaments of cytoskeleton Cholesterol Peripheral

protein Integral protein

CYTOPLASMIC SIDE OF MEMBRANE

EXTRACELLULAR SIDE OF MEMBRANE

Glycolipid

Fibers of extracellular matrix (ECM)

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Why are proteins the perfect

molecule to build structures in the cell membrane?

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Classes of amino acids

What do these amino acids have in common?

nonpolar & hydrophobic

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Classes of amino acids

What do these amino acids have in common?

polar & hydrophilic

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Proteins domains anchor molecule

•  Within membrane –  nonpolar amino acids

•  hydrophobic •  anchors protein

into membrane •  On outer surfaces of membrane

–  polar amino acids •  hydrophilic •  extend into extracellular

fluid & into cytosol

Polar areas of protein

Nonpolar areas of protein

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General functions of cell membrane proteins

1. Provide structural support. 2. Transport molecules across the membrane. 3. Enzymatic control of chemical reactions at cellular surface. 4. Some fx as receptors for hormones. 5. Some fx as regulatory molecules, that arrive at outer surface of the membrane. 6. Some serve as ‘markers’ (antigens), that identify blood & tissue type of an individual.

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Functions of Membrane Proteins

Outside

Plasma membrane

Inside Transporter Cell surface

receptor Enzyme activity

Cell surface identity marker

Attachment to the cytoskeleton

Cell adhesion

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Major functions of membrane proteins

Transport. (left) A protein that spans the membrane may provide a hydrophilic channel across the membrane that is selective for a particular solute. (right) Other transport proteins shuttle a substance from one side to the other by changing shape. Some of these proteins hydrolyze ATP as an energy source to actively pump substances across the membrane.

Enzymatic activity. A protein built into the membrane may be an enzyme with its active site exposed to substances in the adjacent solution. In some cases, several enzymes in a membrane are organized as a team that carries out sequential steps of a metabolic pathway.

Signal transduction. A membrane protein may have a binding site with a specific shape that fits the shape of a chemical messenger, such as a hormone. The external messenger (signal) may cause a conformational change in the protein (receptor) that relays the message to the inside of the cell.

(a)

(b)

(c)

ATP

Enzymes

Signal

Receptor

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Cell-cell recognition. Some glyco-proteins serve as identification tags that are specifically recognized by other cells.

Intercellular joining. Membrane proteins of adjacent cells may hook together in various kinds of junctions, such as gap junctions or tight junctions

Attachment to the cytoskeleton and extracellular matrix (ECM). Microfilaments or other elements of the cytoskeleton may be bonded to membrane proteins, a function that helps maintain cell shape and stabilizes the location of certain membrane proteins. Proteins that adhere to the ECM can coordinate extracellular and intracellular changes .

(d)

(e)

(f)

Glyco- protein

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Overview of major functions of membrane proteins:

–  Transport –  Enzymatic activity –  Signal transduction –  Cell-cell recognition –  Intercellular joining –  Attachment to the Extracellular Matrix (ECM)

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Synthesis and Sidedness of Membranes

•  Membranes have distinct inside and outside faces

•  This affects the movement of proteins synthesized in the endomembrane system

•  Membrane proteins and lipids –  Are synthesized in the ER

and Golgi apparatus

Transmembrane glycoproteins

Secretory protein

Glycolipid

Golgi apparatus

Vesicle

Transmembrane glycoprotein

Membrane glycolipid

Plasma membrane: Cytoplasmic face

Extracellular face

Secreted protein

4

1

2

3

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Cell membrane carbohydrates

•  Primarily attached to the outer surface of the membrane as:

- Glycoproteins … (most of it). - Glycolipids …… (1/10).

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1. Attach cells to each other. 2. Act as receptor substances. 3. Some enter in immune reactions. 4. Give most of cells overall surface charge, which

affects the interaction of regulatory molecules of the membrane.

General functions of cell membrane carbohydrates

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The Role of Membrane Carbohydrates in Cell-Cell Recognition

•  Cell-cell recognition –  Is a cell’s ability to distinguish one type of

neighboring cell from another •  Membrane carbohydrates

–  Interact with the surface molecules of other cells, facilitating cell-cell recognition

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Membrane carbohydrates •  Play a key role in cell-cell recognition

–  ability of a cell to distinguish one cell from another •  antigens

–  important in organ and tissue development –  basis for rejection of foreign cells by

immune system (ex. HLA SYSTEM).

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Transport through the Cell Membrane

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Transport through the Cell Membrane

•  Cell membrane is selectively permeable to some molecules & ions. –  Not permeable to proteins, nucleic acids, & other

molecules.

•  Lipid or fat-soluble substances, e.g. O2, CO2, OH; enter directly into cell membrane through the lipid bilayer.

•  Water-soluble substances, e.g. ions, glucose, water; enter through proteins of the cell membrane.

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Bilayer is Not as Rigid or Static as it is Usually Depicted

Importance of thermal motion at the molecular level

Life is dynamic – constant fluctuations

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Categories of transport through Cell Membrane

–  Carrier mediated transport: –  Non-carrier mediated transport. –  Passive transport:

–  Does not require metabolic energy (ATP).

–  Active transport: –  Requires ATP.

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Types of membrane transport

1. Diffusion (passive transport)

•  net movement of molecules & ions across a membrane from higher to lower conc. (down conc gradient) •  doesn’t require metabolic energy.

2. Active transport

o  net movement across a membrane that occurs against conc gradient. (to region of higher conc)

o  Requires metabolic energy (ATP), & involves specific carrier proteins.

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Types of membrane transport

1. Diffusion (passive transport)

a. Simple diffusion. b. Facilitated

diffusion. (Carrier-mediated)

c. Osmosis.

2. Active transport

a. Primary active transport. b. Secondary active transport.

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1. Diffusion (passive transport) •  Random movement of substance through the

membrane, either directly or in combination w carrier protein down an electrochemical gradient.

a. simple diffusion b. facilitated diffusion c. osmosis

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Diffusion (passive transport)

•  2nd Law of Thermodynamics governs biological systems –  universe tends towards disorder (entropy)

•  Diffusion –  movement from high → low concentration

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Diffusion •  Move from HIGH to LOW concentration

–  “passive transport” –  no energy needed

diffusion osmosis

movement of water

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Diffusion across cell membrane

•  Cell membrane is the boundary between inside & outside… – separates cell from its environment

IN food carbohydrates sugars, proteins amino acids lipids salts, O2, H2O

OUT waste ammonia salts CO2 H2O products

cell needs materials in & products or waste out

IN

OUT

Can it be an impenetrable boundary? NO!

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Diffusion through phospholipid bilayer

•  What molecules can get through directly? –  fats & other lipids

inside cell

outside cell

lipid salt

aa H2O sugar

NH3

•  What molecules can NOT get through directly?

–  polar molecules •  H2O

–  ions •  salts, ammonia

–  large molecules •  starches, proteins

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Channels through cell membrane

•  Membrane becomes semi-permeable with protein channels –  specific channels allow specific material across cell

membrane

inside cell

outside cell

sugar aa H2O

salt NH3

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Facilitated Diffusion

•  Diffusion through protein channels –  channels move specific molecules across

cell membrane –  no energy needed

“The Bouncer”

open channel = fast transport facilitated = with help

high

low

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The Special Case of Water

Movement of water across the cell membrane

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Osmosis is diffusion of water

•  Water is very important to life, so we talk about water separately

•  Diffusion of water from high concentration of water to low concentration of water –  across a

semi-permeable membrane

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Concentration of water

•  Direction of osmosis is determined by comparing total solute concentrations –  Hypertonic - more solute, less water

–  Hypotonic - less solute, more water

–  Isotonic - equal solute, equal water

hypotonic hypertonic

water

net movement of water

AP Biology freshwater balanced saltwater

Managing water balance

•  Cell survival depends on balancing water uptake & loss

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Managing water balance

•  Isotonic –  animal cell immersed in

mild salt solution •  example:

blood cells in blood plasma •  problem: none

–  no net movement of water »  flows across membrane

equally, in both directions –  volume of cell is stable

balanced

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Managing water balance

•  Hypotonic –  a cell in fresh water

•  example: Paramecium •  problem: gains water,

swells & can burst – water continually enters

Paramecium cell

•  solution: contractile vacuole –  pumps water out of cell –  ATP

–  plant cells •  turgid

freshwater

ATP

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Aquaporins

•  Water moves rapidly into & out of cells –  evidence that there were water channels

1991 | 2003 NOBEL P.

AP Biology Peter Agre

John Hopkins Roderick

MacKinnon Rockefeller

GHEORGHE BENGA UMF Cluj Napoca

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Active transport:

•  Protein-Carrier mediated transport.

•  Involves net transport (uphill), i.e. against electrochemical gradient (from lower to higher conc).

•  Requires metabolic energy (ATP).

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Active Transport

“The Doorman”

conformational change

•  Cells may need to move molecules against concentration gradient –  shape change transports solute from

one side of membrane to other –  protein “pump” –  “costs” energy = ATP

ATP

low

high

AP Biology

Types of active transport

I. Primary active transport II. Secondary active transport

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I. Primary Active Transport

•  Energy is supplied directly from hydrolysis of ATP for the fx of the protein carriers.

•  Molecule or ion binds to “recognition site” on one side of carrier protein.

•  Binding stimulates phosphorylation (breakdown of ATP) of carrier protein.

•  Carrier protein undergoes conformational change. –  Hinge-like motion releases

transported molecules to opposite side of membrane.

•  Some of these carriers transport only one molecule or ion for another.

AP Biology

Primary active transport (continued)

•  Examples:

a. Sodium-Potassium pump (Na+/K+ pump).

b. Primary active transport of calcium (Ca2+ ATPase).

c. Primary active transport of hydrogen ions (H+/K+ ATPase)

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Sodium-Potassium pump (Na+/K+ pump):

•  Present in most cell membranes. e.g. in basolateral membrane of the kidneys, & in intestines.

•  Energy dependent transport, because both ions are moved against their conc gradient.

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Na+/K+ Pump

•  Is also an ATP enzyme that converts ATP to ADP and Pi. –  Actively extrudes 3 Na+ &

transports 2 K+ inward against conc gradient.

•  Steep gradient serves 4 fxs: –  Provides energy for “coupled

transport” of other molecules. –  Regulates resting calorie

expenditure & BMR. –  Involvement in

electrochemical impulses. –  Promotes osmotic flow. 3

2

AP Biology

II. Secondary active transport: (Coupled Transport)

•  Transport of one or more solutes against an electrochemical gradient, coupled to the transport of another solute down an electrochemical gradient.

•  Energy needed for “uphill” movement obtained from “downhill” transport of Na+.

•  Hydrolysis of ATP by Na+/K+ pump required indirectly to maintain [Na+] gradient.

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•  If the other molecule or ion is moved in the same direction as Na+ (into the cell), the coupled transport is called either: ‘cotransport’ or ‘symport’.

•  If the other molecule or ion is moved in the opposite direction as Na+ (out of the cell), the process is called either: ‘countertransport’ or ‘antiport’.

Secondary Active Transport (continued)

AP Biology

a. Co-transport (Symport) •  All solutes move in the same direction → “to

the inside of the cell”

•  e.g. - Na+– glucose Co transport - Na+– amino acid Co transport •  In the intestinal tract, & kidney’s brush

borders.

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Na+– glucose Co transport

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b. Counter transport (Antiport)

•  Na+ is moving to the interior causing other substance to move out.

•  e.g. - Ca2+– Na+ exchange … (present in many cell membranes) - Na+– H+ exchange in the kidney - Cl-– HCO3

- exchange across RBCs.

AP Biology symport antiport

Active transport

•  Many models & mechanisms

ATP ATP

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Transport summary

simple diffusion

facilitated diffusion

active transport

ATP

AP Biology

How about large molecules? Bulk transport

•  Bulk transport across the plasma membrane occurs by exocytosis and endocytosis

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Bulk Transport

•  Receptor-mediated endocytosis: –  Interaction of molecules in ECF with specific membrane

receptor proteins. –  Membrane invaginates, fuses, pinches off and forms

vesicle. –  Vesicle enters cell.

•  Exocytosis: –  Process by which cellular products are secreted into

extracellular environment. –  Proteins and other molecules to be secreted are

packaged in vesicles by Golgi complex. –  Vesicles fuse with plasma membrane and release

contents into extracellular environment.

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Phagocytosis:

–  Phagocytic cells use pseudopods to surround and engulf particles.

–  Pseudopods join, fuse, and surround ingested particle (food vacuole).

•  Lysosomes digest food vacuole. –  Protects from invading organisms. –  Removes debris.

Pinocytosis: •  Nonspecific process. •  Plasma membrane invaginates, fuses, vesicle

containing ECF pinches off, and vesicle enters cell.

•  Endocytosis

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Endocytosis

phagocytosis

pinocytosis

receptor-mediated endocytosis

fuse with lysosome for digestion

non-specific process

triggered by molecular signal

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Exploring Endocytosis in Animal Cells

EXTRACELLULAR FLUID

In phagocytosis, a cell engulfs a particle by wrapping pseudopodia around it and packaging it within a membrane- enclosed sac large enough to be classified as a vacuole. The particle is digested after the vacuole fuses with a lysosome containing hydrolytic enzymes.

Pseudopodium CYTOPLASM

“Food” or other particle

Food vacuole

1 µm

Pseudopodium of amoeba

Bacterium

Food vacuole

An amoeba engulfing a bacterium via phagocytosis (TEM).

PHAGOCYTOSIS

PINOCYTOSIS

Pinocytosis vesicles forming (arrows) in a cell lining a small blood vessel (TEM).

0.5 µm

In pinocytosis, the cell “gulps” droplets of extracellular fluid into tiny vesicles. It is not the fluid itself that is needed by the cell, but the molecules dissolved in the droplet. Because any and all included solutes are taken into the cell, pinocytosis is nonspecific in the substances it transports.

Plasma membrane

Vesicle

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RECEPTOR-MEDIATED ENDOCYTOSIS

Receptor

Ligand

Coat protein

Coated pit

Coated vesicle

A coated pit and a coated vesicle formed during receptor- mediated endocytosis (TEMs).

0.25 µm

Plasma membrane

Coat protein

Receptor-mediated endocytosis enables the cell to acquire bulk quantities of specific substances, even though those substances may not be very concentrated in the extracellular fluid. Embedded in the membrane are proteins with specific receptor sites exposed to the extracellular fluid. The receptor proteins are usually already clustered in regions of the membrane called coated pits, which are lined on their cytoplasmic side by a fuzzy layer of coat proteins. Extracellular substances (ligands) bind to these receptors. When binding occurs, the coated pit forms a vesicle containing the ligand molecules. Notice that there are relatively more bound molecules (purple) inside the vesicle, but other molecules (green) are also present. After this ingested material is liberated from the vesicle, the receptors are recycled to the plasma membrane by the same vesicle.