Source: BiochemFFA_1_1.pdf. The entire textbook is available for free from the authors at http://biochem.science.oregonstate.edu/content/biochemistry-free-and-easy
The Bio of Biochemistry
The most obvious thing about living organisms is their astounding diversity. Estimates put the number of eukaryotic species at about 8.7 million, while bacteria account for anywhere between 107 and 109 different species. The number of species of archaea is still uncertain, but is expected to be very large.
These organisms, representing the three great domains of life, together occupy every environmental niche imaginable, from the human gut to the frozen expanses of the Antarctic, and from the rainforests of the Amazon basin to the acid waste washes of gold mines. Some organisms, like the tardigrades (Figure 1.1), or water bears, can withstand incredibly harsh conditions - from a few degrees above absolute zero to 300°F, the vacuum of outer space, and pressures greater than those at the greatest depths of the ocean. In the memorable words of Dr. Ian Malcolm in the movie, Jurassic Park, “Life finds a way”.
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Knowledge out of a mountain of facts
Missing excessive data
Will not really matta
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Despite the differing demands of existence in these widely varied environments, all living things share some common characteristics. The most noticeable of these is that from hummingbirds to humpback whales, from fungi to frogs, and from bacteria to birch trees, all living things are made up of cells. This fact was first discovered by Robert Hooke, in 1665 (Figure 1.2), when he used a microscope to look at a slice of cork and found that it seemed to be made up of tiny chambers that he named cells. Subsequent examination of other living things revealed that they, too, were, without exception, made up of cells. Today, we know that organisms in all three domains of life – bacteria, archaea and eukaryotes, share this property – they are all made up of cells. For some, a single cell is the organism, while others are multicellular, like humans, wombats or weeping willows.
Figure 1.1 - Tardigrade Wikipedia
Figure 1.2 Slices of cork as seen by Hooke
The subject of this book is biochemistry, the science that explains life at the molecular level. The special characteristics of cells influence the unique chemistry of life. It is, thus fitting, to take a quick look at cells, the setting in which the molecular events of life take place.
Figure 1.3 Bacterial cells Wikipedia Figure
“There are living systems; there is no “living matter”. No substance, no single molecule, extracted and isolated from a living being possess, of its own, the aforementioned paradoxical properties. They are present in living systems, only; that is to say, nowhere below the level of the cell.” – Jacques Monod
All cells, no matter what kind, have a plasma membrane that serves as a boundary for the cell, separating it from its surroundings. They also possess a genome made up of DNA that encodes the information for making the proteins required by the cell. To translate the information in the DNA and make the proteins it encodes, all cells have the machinery for protein synthesis, namely, ribosomes and tRNAs. DNA is also the repository of information that gets copied and transmitted to the next generation, allowing living cells to reproduce.
Figure 1.4 - Organization of organisms by metabolic type Wikipedia
All cells also need to be able to obtain and use energy. The source of this energy is different in different organisms (Figure 1.4). Phototrophs are organisms that obtain metabolic energy from light, while chemotrophs get their energy from the oxidation of chemical fuels. Organisms that can capture energy from light or from chemical sources are termed autotrophs (auto=self, troph=nourishing). Others are heterotrophs, which use, as their energy source, the organic compounds made by other organisms. Plants, and other photosynthetic organisms are autotrophs, while animals are heterotrophs.
Figure 1.5 - Tree of life Wikipedia
Cells may be aerobic (i.e., use oxygen) or anaerobic (able to live without oxygen). Some anaerobic cells are obligate anaerobes, that is, they require an environment free of oxygen. Others are facultative anaerobes, cells that can live with, or without, oxygen.
Prokaryotic and eukaryotic cells
Organisms may be divided into two major groups, the prokaryotes and the eukaryotes. The cells of the former lack a nucleus and other organelles, while those of the latter are characterized by numerous internal, membranebounded compartments, including a nucleus.
Figure 1.6 - Interplay between autotrophs and heterotrophs Wikipedia
Prokaryotes are unicellular and generally considerably smaller than their eukaryotic cousins, with sizes ranging from 0.5 to 5 µm in diameter. Prokaryotes typically have circular chromosomes, and may sometimes contain extra-chromosomal DNA elements (also Image by usually circular) called plasmids. Although the DNA in prokaryotes is not wrapped around histones, as is the case for eukaryotes, prokaryotes have proteins associated with their DNA. The DNA-protein complexes in prokaryotes create a structure called a nucleoid, which is different from the eukaryotic nucleus in not being enclosed by a nuclear envelope (Figure 1.7). The proteins associated with the DNA in Archaea resemble eukaryotic histones, while those in bacteria are different from both eukaryotic and archaeal DNA packaging proteins.
Aleia Kim Table 1.1
Prokaryotes may be divided into two broad categories, bacteria and archaea. These single-celled organisms are both ancient and widespread. Archaea were once thought to be a subgroup of bacteria, but have subsequently been shown to be a completely different group of organisms that are so distinct from both bacteria and eukaryotes that they now are classified in a domain of their own.
Like eukaryotic cells, bacterial cells have a plasma membrane surrounding them, but in addition, they also contain an exterior cell wall, comprised of an interlocked peptidoglycan network. On their exterior surfaces, bacteria have hair-like appendages called pili that allow them to adhere to other cells. Pili play an important role in bacterial conjugation, a process in which DNA is transferred between bacterial cells. In addition, bacterial cells may have flagella that enable them to move through their surroundings.
Figure 1.7 - Prokaryotic vs. eukaryotic cell structures (not to scale)
Excuse me for feeling superia
To the life forms we call the bacteria
Students know very well
There are no organelles
To be found in their tiny interia
Interestingly, bacteria can communicate, not only with members of their own species, but also with other bacterial species, using chemical signals, in a process called quorum sensing. These signaling mechanisms enable bacteria to assess conditions around them (such as the size of their population). Quorum sensing plays a role in the process of infection by bacterial pathogens as well as the formation of biofilms (mats of cells that adhere to each other tightly and protect the bacteria against environmental hazards or other harmful agents).
The first archaeans to be studied were all found in harsh environments such as salt flats and hot springs. Because of this, they were initially believed to live only in extreme environments and were described as extremophiles (Figure 1.8). We now know that archaeans can be found in every environment, moderate or extreme. Archaea have been found in the human gut, and in such huge numbers in marine plankton that it has been suggested that they may be the most abundant organisms on earth.
While they are unicellular, and superficially resemble bacteria, archaea are in some respects more similar to eukaryotes. Their transcriptional machinery, promoter sequences and ribosomes are much more like those of eukaryotes than of prokaryotes. Archaea are also unique among living organisms in their use of ether linkages to join the lipids used in their plasma membranes to glycerol. Not only are the ether linkages different from the ester linkages in all other forms of life, but the lipids themselves are different. In place of the fatty acids used in both bacterial and eukaryotic membranes, archaea use long isoprene-derived chains (Figure 1.9) This difference in membrane composition and structure makes archaeal membranes highly stable and may be advantageous in extreme conditions.
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Figure 1.8 - Archaeans growing in acid mine waste
Archaea, like bacteria, also have a cell wall, but the cell walls do not contain peptidoglycans. Some archaea have peptidoglycan-like molecules in their cell walls, while others build their cell walls entirely of glycoproteins and polysaccharides.
Figure 1.9 Archaeal membrane, top, showing unusual ether linkages and isoprene chains and bacterial membrane, below. Wikipedia
Eukaryotic cells are found in both unicellular and multicellular organizational schemes. Unicellular forms include yeast and many protists, familiar to students from introductory biology labs, like Paramecium and Amoeba. Multicellular eukaryotes include plants, animals, and fungi. Eukaryotic cells are surrounded by a plasma membrane. Animal cells have no cell walls, whereas plant cells use cellulose, hemicellulose, and pectins to build cell walls outside their plasma membranes. Fungal cells have cell walls that are unusual in containing the polymer, chitin, which is also found in the exoskeletons of arthropods.
Figure 1.10 Paramecium Wikipedia
Eukaryotic cells are typically much larger (typically 10-100 µm) and contain considerably more DNA than prokaryotic cells. The most distinctive feature of eukaryotic cells, however, is the presence of a variety of internal membrane-bounded structures, called organelles.
Eukaryotic cells are characterized by internal membrane-bounded compartments, or organelles. These compartments divide up the interior of the cell into discrete parts that have specialized functions. Organelles found in eukaryotic cells include the nucleus (houses DNA), mitochondria (electron transport system/ oxidative phosphorylation for ATP synthesis), nucleolus (ribosome synthesis and assembly), endoplasmic reticulum (lipid metabolism and targeted protein synthesis and folding), the Golgi apparatus (protein modification and secretion), peroxisomes (oxidation of very long chain fatty acids), chloroplasts (plants - photosynthesis), plastids (synthesis and storage of compounds in plants), lysosomes (animals - hydrolytic enzymes), endosomes (contain endocytosed material), and vacuoles.
Figure 1.11 Animal cell structure Wikipedia
The presence of multiple compartments within the cell permits reactions requiring specific conditions to be carried out in isolation from the rest of the cell. For example, the formation of disulfide bonds in proteins is possible in the conditions within the endoplasmic reticulum, but would not readily occur in the different environment of the cytosol. The presence of membrane-bounded compartments also allows reactants to be more concentrated because of the smaller volume of the organelle.
Eukaryotic DNA in a cell is divided into several linear bundles called chromosomes. Chromosomes contain the genomic DNA wrapped around cores of positively charged proteins called histones. The ends of linear eukaryotic chromosomes have telomeres, short (less than 10 bp) sequences repeated thousands of times. The role of telomeres in preventing loss of information when linear chromosomes are replicated is discussed later.
The chromosomes in eukaryotic cells are surrounded by the nuclear envelope, a double membrane structure that encloses the nucleus (Figure 1.12). Within the nucleus, there are enzymes required for the replication and transcription of genetic information. The presence of the nuclear envelope also regulates which proteins can enter the nucleus at any given time. This, as you will see later, is an important way to control gene expression.
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Figure 1.12 Cell nucleus
Mitochondria and chloroplasts have their own DNA, separate from and in addition to the nuclear DNA. This DNA is small and circular and resembles a prokaryotic chromosome. Mitochondria and chloroplasts also have their own ribosomes and tRNAs and can carry out their own protein synthesis. This is not as odd as it seems, because these organelles are likely derived from prokaryotes that once lived as endosymbionts within ancient eukaryotic cells and eventually became integrated into their host cells.
Another interesting feature of eukaryotic cells is the presence of an internal skeleton-like structure called a cytoskeleton. The cytoskeleton is made up of a network of interlinking protein fibers belonging to three major classes: microtubules, microfilaments, also known as actin filaments, and intermediate filaments (Figure 1.13). All eukaryotic cells have microfilaments and microtubules, but it appears that plant cells may lack intermediate filaments (It is now known that some cytoskeletal elements are present in bacteria and archaea as well, but these have been discovered relatively recently and thus, less is known about them.)
Although the word “skeleton” may suggest a rigid and fixed structure, the cytoskeleton is dynamic, with both microfilaments and microtubules disassembling and rearranging themselves on an ongoing basis, as needed. Intermediate filaments are also broken down and rebuilt, at specific times, such as during cell division. The three main classes of cytoskeletal elements are distinguished by the proteins that they are composed of, as well as the way in which those proteins assemble into the structures seen in the cell.
Figure 1.13 Cultured cells stained to show intermediate filaments Wikipedia
Intermediate filaments, for example, are made up of a variety of proteins that share a common structure, and assemble into fibers that resemble a cable made up of many individual strands of wire twisted together. This arrangement, because of its mechanical strength, makes intermediate filaments ideally suited to provide structural support to various cell structures. The nuclear envelope, for example, has a network of intermediate filaments called the nuclear lamina, just inside the inner membrane of the envelope in animal cells.
Microfilaments, composed of the protein actin, underlie the plasma membrane of animal cells, and give them their characteristic shapes. Remodeling of these filaments changes the shape of the cell, and is important for cell movement. In animal cells, actin also plays a role in cytokinesis, the last step in cell division, by helping to cleave the cell in two after nuclear division.
Microtubules, made up of various kinds of a protein called tubulin, also play vital roles in cell division (Figure 1.14). The spindle fibers that attach to chromosomes during metaphase, and help separate the two sets of chromosomes, are made up of microtubules. Microtubules also serve as tracks along which motor proteins, like dynein and kinesin, transport cargo to different parts of the cell.
Figure 1.14 - β-tubulin in Tetrahymena Wikipedia
Additional functions of the cytoskeleton include helping to organize the contents of the cell. If you ever wondered what kept organelles in an aqueous cytoplasm from floating around like beach balls in water, the answer is that organelles are anchored by attachment to the cytoskeleton. Interactions among cytoskeletal proteins and components of the extracellular matrix are crucial in maintaining tissue structure. Membrane-associated signaling proteins are sometimes linked to components of the cytoskeleton, giving cytoskeletal proteins a role in cell signaling pathways.
Figure 1.15 - The cytoskeleton. Actin filaments are in red, microtubules in green, nucleus in blue
Cells in multicellular organisms are organized into tissues that play specialized roles in the body. Animals have four types of tissues in their bodies - epithelium, connective tissue, nerve tissue, and muscle tissue. The first of these, epithelial tissues line the cavities and surfaces of blood vessels and organs in the body (Figure 1.16). Epithelial cells are categorized by their shapes: squamous, columnar, and cuboidal. These can be organized in a single cell layer or in layers of two or more cells deep (referred to as stratified or layered). Glands are all comprised of epithelial cells. Epithelial cell functions include protection, secretion, selective absorption, transport, and sensing. Layers of epithelial cells do not contain blood vessels and must receive nutrients through the process of diffusion of materials from underlying connective tissue, through the basement membrane.
Of the four animal tissues, connective tissue is the one that serves as the “glue” to hold everything together. Connective tissue fills the gaps between all the other tissues of the body, including the nervous system. In the central nervous system, for example the outer membranes, the meninges (cover of brain) and the spinal cord are composed of connective tissue. Apart from the blood and lymph, connective tissues contain three main components. They are 1) cells; 2) ground substance; and 3) fibers. Blood and lymph contain components 1 and 2, but not 3. Cell types found in connective tissue include adipocytes, fibroblasts, mast cells, macrophages, and leucocytes.
Figure 1.16 - Types of epithelial tissue
The nervous system of humans contains two main components. The brain and spinal cord comprise the central nervous system (CNS) and nerves branching from these make up the peripheral nervous system. The peripheral nervous system is responsible for regulating bodily functions and actions. In the central nervous system (CNS), the tissue types are referred to as grey matter or white matter. In the peripheral nervous system (PNS), tissue types include nerves and ganglia.
Nerve cells are also called neurons. Neurons can transmit and receive signals. Specialized cells called glia assist in transmitting the nerve signal and also provide nutrients for the neurons. All nerve cells contain an axon (Figure 1.20) which are long fiber-like structures responsible for sending signals in the form of action potentials to adjacent cells. Nervous system functions include receiving input from senses, controlling muscles and glands, homeostasis, integration of information, and mental activity.
Muscle tissue is formed during embryonic development by a process known as myogenesis. Mammals have three types of muscle tissue - 1) skeletal/striated muscle; 2) smooth, non-striated muscle; and 3) cardiac muscle. Cardiac muscle and smooth muscle are notable for contracting involuntarily. Both can be activated through nerve stimuli from the central nervous system or by innervation from the peripheral plexus or by endocrine/hormonal activation. Striated muscles, by contrast, only contract voluntarily by (mostly) conscious action influenced by the central nervous system. Reflexive movement by striated muscles occurs nonconsciously, but also arises from central nervous system stimulation.
Figure 1.17 - Nerve cell anatomy Image by Pehr Jacobson
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