Download Ab`s Simplistic Cell Biology Cell theory is a great example of

Ab’s Simplistic Cell Biology
Cell theory is a great example of reductionism and generalization in biological science.
In the 1700’s biologists noted that animal bodies were made up of compartmentalized globules
of stuff that could be seen under a microscope. In 1809 the French (pre-Darwinian) evolutionist
Jean Baptiste de Lamark declared that all living tissue of all organisms was constructed from
these globules, or cells; in the 1830’s this assertion was confirmed by careful observations. In
the late 1800’s the basic mechanics of cell division were understood, and by 1900 all mainstream
biologists accepted a cellular theory of organization for all living things. This theory posited
that, if cells were general building blocks, then science could develop a single discipline of cell
biology, and that the findings of this discipline would apply to all living organisms. (That is,
science did not need “a biology of mammal cells” and “a biology of insect cells” and “a biology
of plant cells” and “a biology of bacterial cells.” Different organisms might have cells that
differed in details, even in important details—but the generalities of a single cell-science would
apply to all biota, extinct, extant, and future.)
We want to start our consideration of cell biology at a very basic level. Therefore, let’s
begin by thinking about a cell as a “black box” (1) that receives from its environment fuel and
oxygen in which to burn the fuel and (2) returns to that environment CO2 and other “unwanted”
products of digestion.
This is, perhaps, the simplest possible model of cellular metabolism. And we won’t go
into a whole lot more detail, but we should at least have some idea of what goes on within the
“black box” that I have labeled “The Cell.” To do this, we need to have a rough picture of the
structures that comprise a generalized cell (which, for purposes of this course, will be a
generalized eukaryote animal cell). Then we can consider how the cell uses energy. Our
fundamental ideas on energy-flows, developed at this micro-level, may also serve us when we
examine biological processes at the macro-level of ecology. Anyhow, we begin the next page
with a simple schematic of a cell and some of its most important parts.
The Cell and its Parts
So there’s a model of a cell; let’s see what these various components are and do.
Plasma membrane.
This is the border of an animal cell, the demarcation between interior
and exterior. The plasma membrane is basically composed of a phospholipid bilayer: the
hydrophilic, polar, phosphorus-containing “heads” of the constituent molecules are oriented into
the aqueous cytoplasm and outward into the cell’s aqueous environment. The hydrophobic,
fatty-acid “tails” of the molecules are oriented inwards. The cell membrane is not smooth and
even; rather it is spotted with various micro-structures such as membrane proteins and
carbohydrates. Some of these are involved in intercellular cohesion; others allow a given cell to
be recognized by other cells or by extracellular proteins. The cell membrane is also penetrated
by channel proteins. The latter can be involved in passive or active transport of substances into
or out of the cell. Some provide more or less general entre for movement of small to mediumsized molecules; others allow mobility of only specific substances. Among the most important
portal structures are integral membrane glycoproteins involved in the sodium-potassium pump.
One of these structures can break down a molecule of ATP (see below) to bring two K+ ions into
the cell and to eject three Na+ ions. The resulting ionic disequilibria are critical in maintaining
the electronic potentials that allow signaling along nerve-cells.
Cells also need to transport larger stuff across the plasma membrane. This is done by
endocytosis. For particles being ejected, a “bubble” of phospholipid bylayer forms around the
particle; this bubble fuses with the plasma membrane; the outer edge then fractures, releasing the
particle into the extracellular environment. For ingestion, an out-pocket of the plasma membrane
forms around a particle. This structure may fracture within the cell, releasing the particle into the
cytoplasm. Alternatively the structure may persist as a phagosome, which will eventually fuse
with a lysosome (see below) which will complete the digestion of the ingested paraticle.
A particularly important type of endocytosis is called “receptor-mediated.” This allows
an animal cell to capture specific macromolecules from the immediate extracellular environment.
A receptor protein in a shallow pit on the cell’s surface bind with a specific substance (called the
receptor’s ligand). The shallow pit invaginates to form a vesicle around the target-substance,
which is then carried into the cell.
The cytoskeleton. (Structure.)
The cytoskeleton is composed of protein tubules and
microfibers that affect the shape of the cell as well as the movement of organelles within the
cytoplasm. The cytoskeleton also provides “tracks” along which motor-proteins can drag cargoproteins to designated parts of the cell.
Nucleus. (Control.)
The nucleus is the information-center of the cell. It contains the
DNA that carries genetic instructions for synthesizing specific proteins that will be involved in
constructing and organizing the living creature of which the cell is a part. When substances
called promoters bind to a region in the DNA, they cause a segment to uncoil. The uncoiled
segment is then transcribed as an RNA (messenger RNA) template that will then be carried out
of the nucleus to one of the ribosomes, where protein-synthesis will occur. (We’ll talk much
more about transcription and translation this in later classes.)
Ribosomes. (Construction.)
These small structures may be found throughout the
cytoplasm, but they are most common on the surface of the rough endoplasmic reticulum (see
below). Ribosomes are two-part structures that slide along a strand of mRNA (from the “start”
codon, AUG, to the “stop” codon, UAG), reading and fulfilling the requests for amino acids.
Metaphorically, a ribosome works sort of like this: given instructions from mRNA, translationRNA (tRNA) collects a specific set of amino acids and facilitates their linkage into a specific
polypeptide. Various polypeptides are gathered and linked into the specific protein
macromolecules required by the cell’s parent organism.
Ribosomes that are not attached to the endoplasmic reticulum synthesize proteins that are
to be used within the general cytosol. Ribosomes attached to the endoplasmic reticulum
synthesize proteins that are to be used at specific cellular addresses (in specific structures or
organelles) to build protein-structures within cell membranes. They also build some proteins that
are to be exported from the cell. (The ribosomes are not full-time residents of the RER but
attach thereto when they begin to make the sort of protein that the RER will need to process.)
Endoplasmic reticulum. (Packaging.)
For simplicity’s sake my diagram above
shows a cell that is pretty much empty. But actually, in a typical animal cell, much of the
volume is filled with a network of interconnected membranes called the endoplasmic reticulum,
sections of which are called “rough” and “smooth.” Rough endoplasmic reticulum (RER) looks
that way because of the attached ribosomes. RER compartmentalizes the ribosomes’ newly
synthesized polypeptides, completes their organization into proteins (perhaps modifying them a
little), and transports them to specific regions within the cell. Basically, you can think of the
RER (and its associated ribosomes) as the membrane-protein synthesis compartment.
Smooth endoplasmic reticulum (SER) comprises a structure within which molecules are
modified. This includes both proteins from the RER and molecules imported from outside the
cell. (Also in SER, glycogen is hydrolyzed, and lipids and steroids are synthesized.)
Golgi apparatus. (Post Office.) This structure consists of stacks of flattened
membranous sacks and small vesicles that will be budded off. The Golgi apparatus accepts
proteins, which it may or may not modify, from the ER. It sorts and packages these proteins,
routing many of them to the membranes of organelles and of the cell as a whole. (That is, one
main function of the Golgi apparatus is to process membrane-proteins for delivery.)
The Golgi apparatus also processes and packages proteins (usually of RER origin) for
extracellular delivery. This function is particularly important within secretory cells.
Finally, the Golgi apparatus also constructs lysosomes, organelles containing digestive
enzymes that, if mixed in the cytoplasm, would cause substantial damage. Lysosomes are the
sites for intracellular digestion. Typically they fuse with phagosomes that transport food
particles brought into the cell by endocytosis.
Mitochondria. (Power Plant.) In animal cells the metabolism of glucose and other
fuel-molecules begins in the cytosol—but is not in general completed there. Rather, the initial
breakdown products are transported to the mitochondria, where these various molecules with
their varying energetic contents are converted into adenosine triphosphate (ATP), a molecule that
serves as a standardized currency for most cellular work. We’ll say more about this later.
Cells and Energy
We’ll begin at the top of the next page with a restatement of our original energetic model.
You’ll note that we make only the most modest advance, merely replacing a few words with a
representation of the chemical formula, C6H12O6 + 6O2  6CO2+6H2O:
We must eventually improve this formula in several ways; most importantly, let’s
recognize that the burning of fuel in oxygen yields not only water and carbon dioxide, but also
energy, which is used within the cell. We should also remember that overall life-processes of
interest to us result in the production of wastes other than carbon dioxide; these must somehow
be removed from the cell.
Next, we should also recognize that cells burn lots of fuel other than just glucose
(C6H12O6). For now, however, we can focus on glucose, and this is OK for three reasons. First,
the above diagram is a model, and to make a model, scientists often simplify. Second, many
cells do in fact take in lots of glucose. Third, when cells take in other fuels, they often convert it
to glucose before burning it (box).
Enzymes and the conversion of fuel-molecules
One function of a cell’s transcription-translation-protein-assembly machinery is to build
enzymes, proteins with surface-chemical groups that position target-molecules so that chemical
reactions involving them will occur rapidly. An example is the enzyme maltase, a catalyst in the
metabolism of maltose, a 12-carbon fuel-sugar that must be converted to glucose before the
cellular energy-machinery can use it efficiently:
Now, let’s start the hard stuff, attempting to glimpse the use of energy within what is
diagrammatically our cellular black box.
To begin our consideration of cellular energetics, we might think about why a cell would
need energy. I suspect that the list could go on and on, so I’ll just give you a few examples:
1.
2.
3.
4.
5.
Energy is used to build complex molecules.
Energy is used to reshape protein molecules.
Energy is used to transport complex molecules, both within and beyond the cell.
Energy is used to power cell division.
Energy is used to move ions against a density-gradient, thereby powering (among other
things) the electricity in nerve-cells.
6. Energy is used to move cells (as in, for example, the slithering of amoebas or the
contraction of muscle cells).
7. Energy is used to reconfigure energy-rich molecules so that they can be more fully
metabolized (and therefore yield more energy).
Anyhow, here’s the basic theme-song of cellular energetics. Energy-laden fuel molecules
(usually glucose) are oxidized to produce ATP, the convenient, standardized energy-currency
used to power virtually all energy-requiring chemical reactions that allow the cell to live. When
ATP is used, it is thereby down-powered to ADP (adenosine diphosphate; less commonly it is
down-powered further to adenosine monophosphate). Thereafter the ADP is recharged by
energy from a fuel-molecule and thereby readied to support chemical work again:
Schematic: Down-Power, Up-Power ATP Cycle
ATP Formula (note the 3 phosphate groups; ADP has 2, AMP 1)
Metabolism Under Exceptional Circumstances
In general we shall be talking about the complete metabolism of the fuel, glucose, in
oxygen. However, most cells can keep running (at least for a while) when oxygen is not present,
or when a circulatory system cannot deliver oxygen fast enough to keep pace with metabolic
demands. Under these circumstances, glucose is metabolized through anaerobic pathways,
which we shall summarize by the two following equations.
C6H12O6  2C3H6O3 + energy released
C6H12O6  2CH3CH2OH + 2CO2 + energy released
The first equation is for metabolism to lactic acid; the second is for metabolism to ethanol. Both
pathways have many intermediate steps that I have omitted. Also, note that both products still
contain high-energy chemical bonds. (That’s why, for example, we could run cars on ethanol.)
This means, obviously, anaerobic pathways do not harvest all the energy available in a fuelmolecule of glucose. On the other hand, the full metabolism of glucose in oxygen, which we
shall discuss below, harvests much more of the stored chemical energy. If we consider “ATP
energy currency,” then we can quantify this difference. The anaerobic metabolism of a molecule
of glucose, by either of the above pathways, yields 2 molecules of ATP. The aerobic metabolism
of a molecule of glucose yields about 32 molecules of ATP.
Of course you already knew that, sort of. At least you wouldn’t try to run a mile while
holding your breath! In class we’ve already talked a tiny bit about diving in mammals, and I’ve
stated that pulse-rates slow down when mammals are underwater. Do you reckon that has to do
with saving energy so that perhaps a diving mammal might be able to operate a bit longer on
anaerobic energy-harvest? Later in the semester we’ll talk at some length about diving turtles.
These critters slow down their metabolism a whole lot—and some species can stay underwater
for incredible lengths of time. They just don’t let their energy-needs exceed the rate at which
anaerobic metabolism can fulfill them.
The chemical reactions describing the full pathways of complete aerobic metabolism of
glucose are very complex. Indeed, requirements that they be memorized have turned many a
pre-med student into an Accounting or English major. I have occasionally known most of the
formulae, but to tell the truth, I’ve never known ‘em all at the same time! So I certainly won’t
require that of you. But I will give you a bit of vocabulary so that you can at least talk like an
over-worked, traditional bio major. (And, no, such massive feats of memorization are no longer
universally required by biology programs.) In class I’ll talk a little about the following
processes. (Uh, I’m not sure whether I’ve over-simplified or under-simplified; I’m not even sure
whether my simplifications are exactly correct.)
First, in 10 steps, each mediated by a separate enzyme, glucose is broken down. During the first
5 steps of this process chemical energy is invested into the glucose molecule. (I.e., molecules of
ATP are down-powered to ADP as they surrender phosphate groups to the molecule that began
as glucose.) The step-5 product is an energy-rich molecule called glyceraldehyde-3-phosphate,
or G3P. In steps 6-10 G3P gives up some of its chemical energy to become pyruvate (which, as
we shall see, is still pretty energy-rich). The cell harvests this freed energy, recouping its initial
investment and making an energy-profit of two ATP molecules and 2 NADH molecules. (Note
two things. First, pyruvate can be metabolized anaerobically, but that’s a subject that we shall
not explore further. Second, NADH, the reduced form of nicotinamide adenine dinucleotide, is
another energy-currency molecule; it plays several parts in the complete breakdown of glucose
and is a molecule with which hardcore physiologists must be familiar. Right now, we do not
find ourselves in that group.)
These first reactions take place in the cytoplasm; the next reactions take place in the
mitochondria.
Next, pyruvate molecules are oxidized to CO2 (an end-product from which pretty much all the
energy has been sucked) and acetate (which still has considerable harvestable energy). This
process yields some energy-currency NADH.
Yet next, the acetate molecules bind with an enzyme called Coenzyme A to form acetyl CoA,
which enters the citric-acid cycle or Krebs Cycle. This is a set of complex energy-harvesting
reactions in which the acetate is completely oxidized to CO2, completing the breakdown of
glucose. In addition to carbon dioxide, the products are 2 molecules of ATP, 6 molecules of
NADH, and 2 molecules of FADH2 (another energy-currency molecule). As the process runs,
the Coenzyme A is constantly recycled to bind with more acetate molecules and catalyze their
oxidation to CO2.
Finally, electrons from the citric-acid cycle’s NADH and FADH2 are passed through a series of
proteins in the mitochondrion’s inner membrane. (This set of reactions is called the electrontransport chain.) As a result, hydrogen atoms bind with oxygen (making water, a very lowenergy molecule); the energy-molecules NADH and FADH2 are converted to the more
universally useful ATP.
Kenny Rogers’ Gambler insisted that one should not count one’s money “until the dealing’s
done,” but now that a glucose fuel-molecule has been completely broken down, we can reiterate
our initial equation—and count our ATP winnings:
ATP “winnings”: 2 from glycolysis, 2 from the citric-acid cycle, and 28 as a result of NADH and
FADH2 processing in the electron-transport chain for a total of 32, so
Summary equation: C6H12O6 + 6O2  6CO2+6H2O + 32 ATP.
(Here’s a semi-trivia note: In most animal cells the mitochondria involved in the electrontransport chain immediately exact a toll of 2 ATP molecules for moving material across their
boundary membranes, so one could say that in most cases the metabolism of glucose actually
provided a “profit” of 30 ATP recharges.)
Why ATP?
As we have indicated above, ATP provides a unit of energy-currency that is conveniently
packaged for paying the energy-expenses of cellular processes. Here is a four-component
metaphor for you. Ingested fuel-molecules are “monthly paychecks”; ATP is “pocket-money”;
the complex metabolic processes described above are “the bank that accepts paychecks and
makes pocket-money available”; energy-requiring cellular processes are “service-providers and
venders who want correct change only.”
Now, at the risk of sounding excessively silly, I’m going to extend that simplistic
metaphor. For various reasons the cell doesn’t want to have too much money lying around at
any one time. (In more chemical language, ATP is an unstable molecule which, in high
concentrations, would deleteriously alter the chemical balance of the cell.) And yet, in the
course of a day, the cell incurs a whole lot of energy-expenses (box).
If ATP is the cell’s pocket money, then we need to add an ATM to our financial
metaphor—and the cell will be hitting that ATM a whole lot. Depending mostly on your size,
your body maintains at any one time about 50 grams of ATP. (The mass of a Diet Mountain
Dew bottle at the Little Cricket is 591 grams; 50 grams would be like a couple of really big
swallows.) However, during the course of a day, you need to expend approximately your own
weight in ATP! In other words, during a typical day, each ATP molecule in a person’s body is
expended and recharged about 1000-1500 times.
The regulation of the amount of charged ATP in the cell at any given moment provides a
good example of a biological concept that you should understand. That concept is homeostasis,
or “the maintenance of conditions in an approximately stable state.” Anthropomorphically
speaking, the cell does not want to have too much ATP around, but it does need enough to pay
immediate expenses. This production of ATP is regulated at several stages in the metabolic
processes we have outlined above. Let us consider, for example, the initial breakdown of
glucose. One enzyme necessary for the initial steps is the enzyme phosphofractokinase (PFK).
This protein is, of course, produced by the cell, in its ribosomes. But when ATP exists at
excessively high densities (a rare occasion, I admit), the production of PFK is very low. (Cell
biologists say, “High densities of ATP inhibit the production of PFK.) Reduced densities of PFK
slow cellular metabolism and the production of ATP.
On the other hand, when AMP (the one-phosphate, doubly down-powered, over-used
product of ATP expenditure) is present, cellular synthesis of PFK goes into high gear. (Cell
biologists say, “High densities of AMP activate the synthesis of PFK.”) Increased densities of
PFK increase cellular metabolism and the production of ATP.
Mechanisms for the maintenance of homeostasis are sometimes called “negative
feedback mechanisms” because when a system begins to change, these mechanisms tend to
restore the system to its stable state. In a sense, negative feedback mechanisms work like the
thermostat in a house’s heating/cooling system. If the house begins to get too hot, the thermostat
detects that change in conditions and turns on the air conditioner. If the house begins to get too
cool, the thermostat detects that change in conditions and turn on the heater. Negative feedback
mechanisms are common at all biological levels. We have now considered such a system at the
level of the cell. We shall spend a good bit of the semester thinking about thermoregulation:
how does an animal keep from getting too hot or too cold? Obviously this issue involves the
maintenance of homeostasis. Negative feedback mechanisms also exist at the level of
ecosystems. Cellular-level negative feedback systems are very well understood (even if not by
us). Organism-level negative feedback systems are fairly well understood. Unfortunately,
ecosystem-level negative feedback systems are not very well understood. And we’ll begin to
consider this problem over the next couple of weeks.