Human Physiology – Cell structure and function
Physiology – science that describes how organisms FUNCTION and survive in continually changing environments
Levels of Organization:
(Source: Hunter and Borg 2003).
CHEMICAL LEVEL – includes all chemical substances (atoms, ions, & molecules) necessary for life (e.g., genes and proteins or, shown below, a small portion – a heme group – of a hemoglobin molecule); together form the next higher level
Carl Sagan – The Chemistry of Life
CELLULAR LEVEL – cells are the basic structural and functional units of the human body & there are many different types of cells (e.g., muscle, nerve, blood, and so on)
SYSTEM LEVEL – an association of organs that have a common function; there are 11 major systems in the human body, including digestive, nervous, endocrine, circulatory, respiratory, urinary, reproductive, muscular, lymphatic, skeletal, and integumentary.
Cell structure and function
Voyage inside the cell
Two types of cells that make up all living things on earth: prokaryotic and eukaryotic. Prokaryotic cells (check this video) , like bacteria, have no ‘nucleus’, while eukaryotic cells, like those of the human body, do. So, a human cell is enclosed by a cell, or plasma, membrane. Enclosed by that membrane is the cytoplasm (with associated organelles) plus a nucleus.
Structure of a typical bacterium (prokaryote)
Structure of a typical eukaryotic cell
Cell, or Plasma, membrane – encloses every human cell
- Structure – 2 primary building blocks include protein (about 60% of the membrane) and lipid, or fat (about 40% of the membrane). The primary lipid is called phospholipid, and molecules of phospholipid form a ‘phospholipid bilayer’ (two layers of phospholipid molecules). This bilayer forms because the two ‘ends’ of phospholipid molecules have very different characteristics: one end is polar (or hydrophilic) and one (the hydrocarbon tails below) is non-polar (or hydrophobic):
- Functions include:
- The cell is separated from its environment and needs to get nutrients in and waste products out. Some molecules can cross the membrane without assistance, most cannot. Water, non-polar molecules and some small polar molecules can cross. Non-polar molecules penetrate by actually dissolving into the lipid bilayer. Most polar compounds such as amino acids, organic acids and inorganic salts are not allowed entry, but instead must be specifically transported across the membrane by proteins.
- Many of the proteins in the membrane function to help carry out selective transport. These proteins typically span the whole membrane, making contact with the outside environment and the cytoplasm. They often require the expenditure of energy to help compounds move across the membrane
- supporting and retaining the cytoplasm
- being a selective barrier
- communication (via receptors)
At the heart of the immune response is the ability to distinguish between self and nonself.
Every body cell carries distinctive molecules that distinguish it as “self.” Normally the body’s defenses
do not attack tissues that carry a self marker; rather, immune cells coexist peaceably with other body cells in
a state known as self-tolerance (Source: National Cancer Institute).
- Cytoplasm consists of a gelatinous solution and contains microtubules (which serve as a cell’s cytoskeleton) and organelles (literally ‘little organs’)
The three fibers of the cytoskeleton–microtubules in blue, intermediate filaments in red, and actin in green–play countless roles in the cell.
In these cells, actin filaments appear light purple, microtubules yellow, and nuclei greenish blue.
|The cyotoskeleton represents the cell’s skeleton. Like the bony skeletons that give us stability, the cytoskeleton gives our cells shape, strength, and the ability to move, but it does much more than that. The cytoskeleton is made up of three types of fibers that constantly shrink and grow to meet the needs of the cell: microtubules, microfilaments, and actin filaments. Each type of fiber looks, feels, and functions differently. Microtubules consists of a strong protein called tubulin and they are the ‘heavy lifters’ of the cytoskeleton. They do the tough physical labor of separating duplicate chromosomes when cells copy themselves and serve as sturdy railway tracks on which countless molecules and materials shuttle to and fro. They also hold the ER and Golgi neatly in stacks and form the main component of flagella and cilia.
Microfilaments are unusual because they vary greatly according to their location and function in the body. For example, some microfilaments form tough coverings, such as in nails, hair, and the outer layer of skin (not to mention animal claws and scales). Others are found in nerve cells, muscle cells, the heart, and internal organs. In each of these tissues, the filaments are made of different proteins.
Actin filament are made up of two chains of the protein actin twisted together. Although actin filaments are the most brittle of the cytoskeletal fibers, they are also the most versatile in terms of the shapes they can take. They can gather together into bundles, weblike networks, or even three-dimensional gels. They shorten or lengthen to allow cells to move and change shape. Together with a protein partner called myosin, actin filaments make possible the muscle contractions necessary for everything from your action on a sports field to the automatic beating of your heart. (Source: NIGM).
Inner life of a cell (microtubules start at about 3:20)
- Cells also contain a nucleus within which is found DNA (deoxyribonucleic acid) in the form of chromatin (or chromosomes during cell division) plus nucleoli (within which ribosomes are formed)
Chromatin & chromosomes
- Organelles include:
- comes in 2 forms: smooth and rough; the surface of rough ER is coated with ribosomes; the surface of smooth ER is not
- functions include: mechanical support, synthesis (especially proteins by rough ER), and transport
- Endoplasmic reticulum –
The endoplasmic reticulum (ER) is a special membrane structure found only in eukaryotic cells. Some ER has ribosomes on the surface (rough endoplasmic reticulum) –the cell’s protein-making machinery. Proteins that require special conditions or are destined to become part of the cell membrane are processed in the ER and then handed off to another organelle called the Golgi apparatus. The Golgi functions as a cellular post office. Proteins that arrive there are sorted, packaged and transported to various destinations in the cell. Scientists are studying many aspects of the ER and Golgi apparatus, including a built-in quality control mechanism cells use to ensure that proteins are properly made before leaving the ER (Source: NSF).
- Golgi complex (check these animations:
- consists of a series of flattened sacs (or cisternae)
- functions include: synthesis (of substances likes phospholipids), packaging of materials for transport (in vesicles), and production of lysosomes
- Lysosomes (check this animation: http://highered.mcgraw-hill.com/olc/dl/120067/bio01.swf)
- membrane-enclosed spheres that contain powerful digestive enzymes
- functions include destruction of damaged cells (which is why they are sometimes called ‘suicide bags’) & digestion of phagocytosed materials (such as bacteria)
- Mitochondria –
- have a double-membrane: outer membrane & highly convoluted inner membrane (check this NSF video about mitochondria).
- inner membrane has folds or shelf-like structures called cristae that contain elementary particles; these particles represent an enzyme important in ATP production
- primary function is production of adenosine triphosphate (ATP)
Mitochondria are found exclusively in eukaryotic cells. These organelles are often called the “power plants” of the cell because their main job is to make energy (ATP). Mitochondria are highly unusual–they contain their own genetic material and protein-making machinery enwrapped in a double membrane. Many scientists believe mitochondria were once free-living bacteria that colonized complex cells sometime during evolution. (Source: NSF).
- composed of rRNA (ribosomal RNA) & protein
- may be dispersed randomly throughout the cytoplasm or attached to surface of rough endoplasmic reticulum
- often linked together in chains called polyribosomes or polysomes
- primary function is to produce proteins
- Centrioles –
- paired cylindrical structures located near the nucleus
- play an important role in cell division
Mitosis (cell division)
Mitosis and the role of centrioles
- Flagella & cilia – hair-like projections from some human cells
- cilia are relatively short & numerous (e.g., those lining trachea)
- a flagellum is relatively long and there’s typically just one (e.g., sperm)
Functions of cilia
Ovulation (role of cilia explained beginning at about 1:40)
- Villi – projections of cell membrane that serve to increase surface area of a cell (which is important, for example, for cells that line the intestine)
DNA (Deoxyribonucleic acid) – controls cell function via transcription and translation (in other words, by controlling protein synthesis in a cell)
The DNA stored in the nucleus of a single human cell spans over six feet in length if stretched from end to end. Made up of four chemical building blocks called A, C, T and G, for short, DNA contains the instructions for making all living things. The building blocks link to form the molecule’s famous “double helix” structure, which allows genetic information to be copied and passed down from one generation to the next. Occasionally exposure to toxins or malfunction of cellular processes, among other things, does cause copying mistakes. Such changes over long time periods provide opportunities for organisms to adapt to new surroundings–or, cause them to die out. Discrete segments of DNA, called genes, encode the instructions for making proteins. Work horses of the cell, proteins serve as structural material, hormones, enzymes and neurotransmitters as well as play many other roles. (Source: NSF).
|Tucked away inside the DNA of all of your genes are the instructions for how to construct a unique individual. Our genetic identity is “coded” in the sense that four building blocks, called nucleotides, string together to spell out a biochemical message—the manufacturing instructions for a protein. DNA’s four nucleotides, abbreviated A, T, G, and C, can only match up in specific pairs: A links to T and G links to C. An intermediate in this process, called mRNA (messenger ribonucleic acid), is made from the DNA template and serves as a link to molecular machines called ribosomes. Inside every cell, ribosomes read mRNA sequences and hook together protein building blocks called amino acids in the order specified by the code: Groups of three nucleotides in mRNA code for each of 20 amino acids. Connector molecules called tRNA (transfer RNA) aid in this process. Ultimately, the string of amino acids folds upon itself, adopting the unique shape that is the signature of that particular protein.||
Transcription – DNA is used to produce mRNA (check this flash animation:
Translation – mRNA then moves from the nucleus into the cytoplasm & is used to produce a protein (check this animation: translation and this video)
- requires mRNA, tRNA (transfer RNA), amino acids, & a ribosome
From RNA to protein synthesis
tRNA molecule Used with permission of John Kimball
- sequence of amino acids in a protein is determined by sequence of codons (mRNA). Codons are ‘read’ by anticodons of tRNAs & tRNAs then ‘deliver’ their amino acid.
- Amino acids are linked together by peptide bonds (see diagram to the right)
- As mRNA slides through ribosome, codons are exposed in sequence & appropriate amino acids are delivered by tRNAs. The protein (or polypeptide) thus grows in length as more amino acids are delivered.
- The polypeptide chain then ‘folds’ in various ways to form a complex three-dimensional protein molecule that will serve either as a structural protein or an enzyme.
Used with permission of John Kimball
COMPONENTS OF THE CELLULAR ENVIRONMENT
- comprises 60 – 90% of most living organisms (and cells)
- important because it serves as an excellent solvent & enters into many metabolic reactions
Ions = atoms or molecules with unequal numbers of electrons and protons:
- found in both intra- & extracellular fluid
- examples of important ions include sodium, potassium, calcium, and chloride
- about 3% of the dry mass of a typical cell
- composed of carbon, hydrogen, & oxygen atoms (e.g., glucose is C6H12O6)
- an important source of energy for cells
- types include:
- 2 monosaccharides linked together
- Examples include sucrose (a common plant disaccharide is composed of the monosaccharides glucose and fructose) & lactose (or milk sugar; a disaccharide composed of glucose and the monosaccharide galactose)
- several monosaccharides linked together
- Examples include starch (a common plant polysaccharide made up of many glucose molecules) and glycogen (commonly stored in the liver)
- monosaccharides (e.g., glucose) – most contain 5 or 6 carbon atoms
- about 40% of the dry mass of a typical cell
- composed largely of carbon & hydrogen
- generally insoluble in water
- involved mainly with long-term energy storage; other functions are as structural components (as in the case of phospholipids that are the major building block in cell membranes) and as “messengers” (hormones) that play roles in communications within and between cells
- Subclasses include:
- triglycerides – consist of one glycerol molecule + 3 fatty acids (e.g., stearic acid in the diagram below). Fatty acids typically consist of chains of 16 or 18 carbons (plus lots of hydrogens).
- phospholipids – a phosphate group (-PO4) substitutes for one fatty acid & these lipids are an important component of cell membranes
- steroids – include testosterone, estrogen, & cholesterol
- about 50 – 60% of the dry mass of a typical cell
- subunit is the amino acid & amino acids are linked by peptide bonds
- 2 functional categories = structural (proteins part of the structure of a cell like those in the cell membrane) & enzymes
- Enzymes are catalysts. Enzymes bind temporarily to one or more of the reactants of the reaction they catalyze. In doing so, they lower the amount of activation energy needed and thus speed up the reaction (check this animation – How enzymes work).
Used by permission of John W. Kimball
- RNA (including mRNA, tRNA, & rRNA)
Movement Across Membranes (videos – Active and passive transport & osmosis):
1 – Passive processes – require no expenditure of energy by a cell:
- Simple diffusion = net movement of a substance from an area of high concentration to an area of low concentration (check this animation – How diffusion works). The rate of diffusion is influenced by:
- concentration gradient
- cross-sectional area through which diffusion occurs
- molecular weight of a substance
- distance through which diffusion occurs
- Osmosis = diffusion of water across a semipermeable membrane (like a cell membrane) from an area of low solute concentration to an area of high solute concentration (Check this animation – How osmosis works and check rbl.cvmbs.colostate.edu/hbooks/cmb/cells/pmemb/osmosis.html for more information about osmosis)
- Facilitated diffusion = movement of a substance across a cell membrane from an area of high concentration to an area of low concentration (check this animation – How facilitated diffusion works). This process requires the use of ‘carriers’ (membrane proteins). In the example below, a ligand molecule (e.g., acetylcholine) binds to the membrane protein. This causes a conformational change or, in other words, an ‘opening’ in the protein through which a substance (e.g., sodium ions) can pass.
2 – Active processes – require the expenditure of energy by cells:
- Active transport = movement of a substance across a cell membrane from an area of low concentration to an area of high concentration using a carrier molecule
Active Transport: The Sodium-Potassium Pump
Used with permission of Gary Kaiser
- Endo- & exocytosis – moving material into (endo-) or out of (exo-) cell in bulk form
Endo- and exocytosis
Used with permission of Gary Kaiser
An example of endocytosis (by a white blood cell called a neutrophil)
Shown here is one way that active transport can occur. Initially, the membrane transport protein (also called a carrier) is in its closed configuration which does not allow substrates or other molecules to enter or leave the cell. Next, the substance being transported (small red spots) binds to the carrier at the active site (or binding site). Then, on the inside of the cell, ATP (Adenosine TriPhosphate) binds to another site on the carrier and phosphorylates (adds one of its phospate groups, or -PO4, to) one of the amino acids that is part of the carrier molecule. This attachment of a phosphate group to the carrier molecule causes a conformational change in (or a change in the shape of ) the protein so that a channel opens between the inside and outside of the cell membrane. Then, the substrate can enter the cell. As one molecule of substrate enters, the phosphate group comes off the carrier and the carrier again ‘closes’ so that no other molecules can pass through the channel. Now the transport protein, or carrier, is ready to start the cycle again. Note that as materials are transported into the cell, ATP is used up and ADP and -PO4 accumulate. More ATP must be made by glycolysis and the Kreb’s cycle.
Characteristics of Facilitated Diffusion & Active Transport – both require the use of carriers that are specific to particular substances (that is, each type of carrier can ‘carry’ one type of substance) and both can exhibit saturation (movement across a membrane is limited by number of carriers & the speed with which they move materials; see graph below).
Cells require energy for active transport, synthesis, impulse conduction (nerve cells), contraction (muscle cells), and so on. Cells must be able to ‘capture’ and store energy & release that energy in appropriate amounts when needed. An important source of energy for cells is glucose (C6H12O6):
View of the ATP/ADP carrier (AAC) from the cytoplasm, with the ADP molecule (blue, aqua, red and white spheres)
at the entrance, ready to be funneled into the carrier.
(Credit: Image courtesy of Emad Tajkhorshid and Yi Wang, U. of Illinois)
Exchange of ATP and ADP across the mitochondrial membrane replenishes the cytoplasm with newly synthesized ATP and provides the mitochondria with the substrate ADP for oxidative phosphorylation. This exchange requires a molecule known as AAC (ADP/ATP carrier). AAC is a membrane protein that acts like a revolving door – transporting ADP into mitochondria (to be converted to ATP) and ATP out of mitochondria and into the cytoplasm (Wang and Tajkhorshid 2008).
The energy released in this reaction (ATP —> ADP) is used by cells for active transport, synthesis, contraction, and so on. Cells need large amounts of ATP &, of course, must constantly make more. But, making ATP requires energy. The breakdown of glucose does release energy. But, how, specifically, is the energy released in the breakdown of glucose used to make ATP?
As glucose is metabolized some ATP is produced because the energy released in some reactions is sufficient to convert ADP + P into ATP (phosphorylation). However, most of the ATP produced from glucose is derived from hydrogens that are released as glucose is metabolized. These hydrogens form molecules of NADH and FADH2 that, in mitochondria, are then used to make ATP.
In mitochondria, the hydrogens associated with NADH and FADH2 are acted upon by enzymes that cause the release of their electrons to create a hydrogen ion (H+).
The electrons are then passed, in a series of reactions driven by enzymes, from protein to protein (and these proteins are located in the inner membrane of mitochondria) in what is called the electron transport chain. As these electron transfer reactions occur, energy is released that is used to pump the hydrogen ions across that membrane and into the area between the two mitochondrial membranes. This creates a concentration gradient that causes the hydrogen ions to pass back through the inner membrane and, specifically, through an enzyme called ATP synthase. This flow of hydrogen ions causes the ATP synthase molecule to rotate and this, in turn, converts ADP + P into ATP (a reaction called phosphorylation). So, what occurs in mitochondria involves electron transfer (or oxidation; the loss or transfer of an electron) + phosphorylation, or, in other words, oxidative phosphorylation. Oxidative phosphorylation produces lots of energy, but requires hydrogen (NADH and FADH2).
Mitochondrial electron transport chain. Notice that the ‘chain’ of reactions that occurs with the conversion of NADH to NAD+ result in the transport of three pairs of hydrogens (2H+) (that will then result in the production of 3 ATP), whereas the reactions occuring after the conversion of FADH2 to FAD result in the transport of two 2H+ (that will then result in the production of 2 ATP) (Source: Wikipedia).
The cellular metabolism of substrates such as glucose and fatty acids (green arrows in the figure) generates hydrogens and, specifically, hydrogen carriers — NADH and FADH2. NADH and FADH2 donate electrons to the electron-transport chain (check this animation) that consists of proteins located in the mitochondrial inner membrane. Electrons are ultimately transported to molecular oxygen that is reduced to water in the last step of the electron-transport chain. As electrons are transferred along the electron-transport chain, the energy released is used to pump protons (H+) from the mitochondrial matrix into the mitochondrial intermembrane space. The energy produced drives the synthesis of ATP from ADP and inorganic phosphate (Pi) by ATP synthase. ATP is then made available to the cell for various processes (e.g., active transport) that require energy (Source: Krauss et al. 2005).
ATP synthase. The proton channel and rotating stalk are shown in blue.
ATP synthase converts ADP + P into ATP.
Electron transport chain
Where do the hydrogens (NADH and FADH2) come from?
Sources include GLYCOLYSIS and the KREB’S CYCLE.
Glycolysis involves the breakdown of glucose. Cells obtain glucose from the blood. Blood glucose levels are maintained by the interaction of two processes: glycogenesis and glycogenolysis. Glycogenesis is the production of glycogen from glucose and occurs (primarily in the liver and skeletal muscles) when blood glucose levels are too high (for example, after a meal).
Glucose taken up by cells from the blood is used to generate energy in a process called glycolysis.
Glycolysis & the Kreb’s Cycle (Source: Wikipedia)
Overall, glycolysis can be summarized as:
Next comes an intermediate step (called oxidative decarboxylation):
Used with permission of Gary Kaiser
Finally, comes the Kreb’s Cycle:
Overall, therefore, the Kreb’s cycle produces 24 ATP (2 direct & 22 indirect).
OVERALL ATP PRODUCTION from glucose = 8 (from glycolysis) + 6 (from the hydrogens produced when the 2 pyruvic acid are converted into 2 acetyl CoA) + 24 (from the Kreb’s cycle) for a GRAND TOTAL OF 38:
Glucose (carbohydrates) are not the only source of energy for cells. Fats (or lipids), like triglycerides, are also metabolized to produce energy.
Triglycerides —-> Glycerol + Fatty Acids:
- Glycerol —-> Glyceraldehyde —-> Pyruvic Acid —-> Acetyl CoA —-> Kreb’s Cycle
- Fatty Acids are converted into molecules of Acetyl CoA in a process called BETA OXIDATION.
Proteins are also used as a source of energy.
Proteins are first broken down into amino acids. The nitrogen component of amino acids is then removed (in a reaction called DEAMINATION), and these deaminated amino acids are then converted into Acetyl CoA which passes through the Kreb’s Cycle to make more ATP.
Used with permission of Gary Kaiser