BIO 301
Human Physiology

Cell Structure & Function


Cell membranes | Cells, cytoplasm, & organelles | DNA & protein synthesis | Cell environment | Movement across membranes | Cellular metabolism


Evolution

 
Human evolution


Human prehistory


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


Source: http://cwx.prenhall.com/bookbind/pubbooks/hillchem3/medialib/media_portfolio/text_images/CH25/FG25_07.JPG


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)


Source: http://www.nigms.nih.gov/news/science_ed/whatart1.html

TISSUE LEVEL - a tissue is a group of cells that perform a specific function and the basic types of tissues in the human body include epithelial, muscle, nervous, and connective tissues

ORGAN LEVEL - an organ consists of 2 or more tissues that perform a particular function (e.g., heart, liver, stomach, 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)
(Source: en.wikipedia.org/wiki/Prokaryote).


Structure of a typical eukaryotic cell
(Source: training.seer.cancer.gov/module_anatomy/unit2_1_cell_functions_1.html)

Cell, or Plasma, membrane - encloses every human cell

 


Cell membrane 

 
Cell membrane

 

Passive transport


Active transport


Source: http://bio.winona.msus.edu/berg/ANIMTNS/Recep.htm


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).

 


Source: http://www.emc.maricopa.edu/faculty/farabee/BIOBK/BioBookCELL2.html

 

Cells, cytoplasm, and organelles (check this website - Cells Alive) :


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)  

 
Cytoskeleton


 

 
Chromatin & chromosomes
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).

 


Endoplasmic reticulum


Source: Wikipedia

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).

 

 
Mitosis (cell division)

 

Mitosis and the role of centrioles


(Source: www.eeob.iastate.edu/faculty/DrewesC/htdocs/INT-ANIMA-cilium-ONE.htm)


Functions of cilia  


Ovulation (role of cilia explained beginning at about 1:40)

 

 


Small intestine


DNA (Deoxyribonucleic acid) - controls cell function via transcription and translation (in other words, by controlling protein synthesis in a cell)


DNA

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.

(Source: NIGMS)


Source: www.ornl.gov/hgmis/publicat/primer/fig5.html


Transcription

Transcription - DNA is used to produce mRNA (check this flash animation: www.stolaf.edu/people/giannini/flashanimat/molgenetics/transcription.swf)


Source: http://www.nytimes.com/2003/01/21/science/21RNA.html

Translation - mRNA then moves from the nucleus into the cytoplasm & is used to produce a protein (check this animation: translation and this video)

 

RNA transcription

 
From RNA to protein synthesis

 

Translation

tRNA molecule

Used with permission of John Kimball



Used with permission of John Kimball
 
 


Source: http://www.acsu.buffalo.edu/~jbarnard/GtRNA.html

 
Protein structure


Protein folding


COMPONENTS OF THE CELLULAR ENVIRONMENT

Water:

Ions = atoms or molecules with unequal numbers of electrons and protons: Carbohydrates:

Lipids:

 

Proteins:


Used by permission of John W. Kimball

Nucleic Acids:


Movement Across Membranes

1 - Passive processes - require no expenditure of energy by a cell:

2 - Active processes - require the expenditure of energy by cells:

 
Active transport


Active Transport: The Sodium-Potassium Pump

Used with permission of Gary Kaiser

 
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).


CELLULAR METABOLISM:

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):

C6H12O6 + O2 ----------> CO2 + H2O + ENERGY

However, this reaction releases huge amounts of energy (for a cell). So, cells gradually break down glucose in a whole series of reactions & use the smaller amounts of energy released in these reactions to produce ATP (Adenosine Triphosphate) from ADP (Adenosine Diphosphate). Then, cells can break down ATP (as in this reaction):

A----P++P++P <-----> A----P+++P + P + 7300 calories (per mole of ATP, or ~507 gms)





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.
(Source: en.wikipedia.org/wiki/Oxidative_phosphorylation)



Electron transport chain

 
ATP synthase

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).

Glycogenolysis is the reverse process - the breakdown of glycogen to release individual molecules of glucose. This occurs when blood glucose levels begin to decline (for example, several hours after a meal). The interaction of these two processes tends to keep blood glucose levels relatively constant.

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)

In the first few steps of glycolysis, glucose is converted into fructose-1,6-diphosphate. These reactions, like all chemical reactions, involve making and breaking bonds between atoms, and this sometimes requires energy. Even though glycolysis, overall, releases energy, some energy must be added initially to break the necessary bonds and get the energy-producing reactions started. This energy is called activation energy. In the above diagram, energy (i.e., a molecule of ATP) is needed at steps 1 & 3. So, before the energy-producing reactions of glycolysis begin, a cell must actually use two molecules of ATP.

Overall, glycolysis can be summarized as:

Glucose ----> 2 Pyruvic Acid (or pyruvate) + 2 net ATP + 2 NADH

So, glycolysis produces 2 direct ATP (ATP produced directly from the reactions that occur during glycolysis) and 6 indirect ATP (the 2 NADH produced in glycolysis will subsequently go through oxidative phosphorylation and produce 3 ATP per NADH molecule, or 6 ATP). Thus, glycolysis produces a total of 8 ATP.

Next comes an intermediate step (called oxidative decarboxylation):


Used with permission of Gary Kaiser

the 2 Pyruvic Acid are converted into 2 Acetyl CoA & these reactions produce 2 molecules of NADH. Those NADH molecules go through oxidative phosphorylation and produce 6 more ATP (3 ATP per NADH).

Finally, comes the Kreb's Cycle:

2 Acetyl CoA go through this cycle of reactions and produce 2 ATP (= GTP in the above diagram) + 6 NADH + 2 FADH2 plus the waste products carbon dioxide + water. The 6 molecules of NADH are then used to produce 18 ATP (3 ATP per NADH), and the 2 FADH2 molecules generate 4 more ATP.

 

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:
 

Direct
Indirect (O.P.)
TOTAL
Glucose ----> 2 Pyruvic Acid
2
6
8
2 Pyruvic Acid ----> 2 Acetyl CoA
0
6
6
2 Acetyl CoA ----> CO2 + H2O
2
22
24

Overall Total = 38 ATP


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:

This reaction not only produces lots of Acetyl CoA (or acetate), but lots of hydrogens. The Acetyl CoA goes through the Kreb's Cycle, while the hydrogens go through Oxidative Phosphorylation.
 

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


Related (and Useful) Links:

Cell Biology Topics

Cell Organelles

DNA Workshop: You Try It

Macromolecules

Protein Synthesis

Cellular Organization


Back to the BIO 301 syllabus
 

Lecture Notes 2 - Neurons & the Nervous System I

Lecture Notes 2b - Neurons & the Nervous System II

Lecture Notes 3 - Muscle

Lecture Notes 4 - Blood & Body Defenses I

Lecture Notes 4b - Blood & Body Defenses II

Lecture Notes 5 - Cardiovascular System

Lecture Notes 6 - Respiratory System


Literature cited

Hunter, P. J. and T. K. Borg. 2003. Integration from proteins to organs: the Physiome Project. Nature Reviews Molecular Cell Biology 4: 237-243.

Krauss, S., C.-Y. Zhang, and B. B. Lowell. 2005. The mitochondrial uncoupling-protein homologues. Nature Reviews Molecular Cell Biology 6: 248-261.

Wang, Y. and E. Tajkhorshid. 2008. Electrostatic funneling of substrate in mitochondrial inner membrane carriers. Proceedings of the National Academy of Science USA 105: 959809603.