Cellular biology 1 INTRODUCTION • Specialized intracellular membrane-bound organelles (Fig. 1.2), such as mitochondria, Golgi apparatus, endoplasmic reticulum (ER). This chapter is an overview of eukaryotic cells, addressing • Large size (relative to prokaryotic cells). their intracellular organelles and structural components. A basic appreciation of cellular structure and function is important for an understanding of the following chapters’ information concerning metabolism and nutrition. For fur- ther detailed information in this subject area, please refer to EUKARYOTIC ORGANELLES a reference textbook. Nucleus The eukaryotic cell The nucleus is surrounded by a double membrane (nuclear Humans are multicellular eukaryotic organisms. All eukary- envelope). The envelope has multiple pores to allow tran- otic organisms are composed of eukaryotic cells. Eukaryotic sit of material between the nucleus and the cytoplasm. The cells (Fig. 1.1) are defined by the following features: nucleus contains the cell’s genetic material, DNA, organized • A membrane-limited nucleus (the key feature into linear structures known as chromosomes. As well as differentiating eukaryotic cells from prokaryotic cells) chromosomes, irregular zones of densely staining material that contains the cell’s genetic material. are also present. These are the nucleoli, which are responsible Inner nuclear Nucleus membrane Nucleolus Inner Outer Outer mitochondrial nuclear mitochondrial membrane membrane membrane Ribosome Intermembrane space Chromatin Mitochondrial Rough matrix Mitochondrial Nuclear endoplasmic ribosome pore reticulum Crista Mitochondrial mRNA Smooth Vesicle endoplasmic Mitochondrion Circular reticulum mitochondrial Proteins of the DNA Vesicle budding electron transport off rough ER Vesicles fusing system with trans face of Cytoplasm Golgi apparatus ‘Cis’ face + discharging protein/lipid Golgi apparatus ‘Trans’ face Lysosome Vesicles leaving Golgi with modified protein/lipid cargo Cell membrane Fig. 1.1 Ultrastructure of a typical eukaryotic cell and structure of important intracellular organelles. ER, Endoplasmic reticulum. 1 Cellular biology Extracellular Membrane- Rough ER fluid spanning Peripheral protein Hydrophobic integral protein Rough ER is far more abundant than smooth ER. It is dis- (external face) interior tinguished from smooth ER on electron microscopy by the Cholesterol presence of membrane-associated ribosomes (presenting a ‘rough’ appearance). The ribosomes intermittently attach/ detach to the rough ER. Attachment occurs when ribosomes bind with mRNA strands (see Chapter 9) that encode pro- Peripheral protein teins destined for secretion. The developing polypeptide is (internal face) extruded into the rough ER interior, where it may remain to Phospholipid Phospholipid hydrophobic hydrophilic complete its development (see Chapter 9). Alternatively, na- Cytoplasm ‘tail’ groups ‘head’ groups scent proteins may be transported via vesicles to the Golgi apparatus or another destination for further posttranslation Fig. 1.2 Cross-section of a typical cell membrane. Note the modifications. phospholipid bilayer membrane and integral and peripheral proteins. Smooth ER Smooth ER differs from rough ER by the absence of for ribosomal RNA (rRNA) synthesis and ribosome assem- ­membrane-bound ribosomes. The main function of bly. Messenger RNA (mRNA) synthesis (translation of ge- smooth ER is lipid synthesis – assembling phospholip- netic material; see Chapter 9) occurs within the nucleus. ids, steroids and other lipids. It is therefore more abun- mRNA can then exit the nucleus via the nuclear pores into dant in cell types with secretory roles. The large surface the cytoplasm. area of the convoluted structure also presents a useful intracellular surface for enzyme attachment, for example, Mitochondrion ­glucose-6-phosphatase, a key enzyme in gluconeogenesis (see Chapter 5). Smooth ER also plays an important role in The ultrastructure of a mitochondrion is illustrated in attaching nascent receptors to membrane proteins prior to Fig. 1.2. Mitochondria are present in all human cells except their membrane insertion. mature red blood cells. Mitochondria are semiautonomous, self-replicating organelles. They are separated from the cy- toplasm by a double membrane, the inner membrane being Golgi apparatus highly folded into inward-projecting ‘cristae’. Because of its large size, the Golgi apparatus (Fig. 1.2) was The inner membrane is the location of the electron one of the first identified intracellular organelles. It is a sys- transport chain (see Chapter 4), where oxidative phosphor- tem of 5 to 8 cup-shaped interconnected membranous sacs ylation takes place. This is the main role of mitochondria; that receive vesicles containing lipids and proteins from the oxidative phosphorylation is responsible for the vast ma- smooth and rough ER, respectively. It modifies these mol- jority of adenosine triphosphate (ATP) production. ATP is ecules in various ways and then distributes them to appro- the intracellular energy currency used to ‘power’ nearly all priate areas within the cell, packaged within vesicles. The intracellular endergonic reactions. The tricarboxylic acid overall structure possesses a ‘cis’ and a ‘trans’ face. The cis (TCA) cycle (see Chapter 3) is another extremely important face is the ‘entry’ portal to the Golgi apparatus, and ­modified metabolic pathway that occurs only in the mitochondrial molecules exit at the trans face. The Golgi apparatus has an- matrix. other important function – it manufactures lysosomes. Mitochondria contain mitochondrial versions of RNA and ribosomes, and synthesize their own proteins coded for by distinct mitochondrial DNA. This DNA is arranged in Lysosomes and peroxisomes circular form, rather than the chromosome structure seen The cytoplasm contains two different types of specialized in the nucleus. single-membrane-bound vesicular structures: lysosomes and peroxisomes. These differ by their enzyme contents. Endoplasmic reticulum The endoplasmic reticulum (ER) is a complex series of in- Lysosomes terconnected, flattened membranous sacs or ‘cisternae’. The Lysosomes are spherical membrane-bound vesicles with an ER possesses a double membrane, the interior of which is acidic (pH 4–5) interior. They are the intracellular spaces contiguous with the intermembrane space of the double- for enzyme-mediated degradation of obsolete intracellular membraned nucleus at distinct points. Intracellular ER is molecules or imported extracellular material. They are de- divided into two types: rough and smooth. Both smooth rived from the trans face of the Golgi. Lysosomes are highly and rough ER are continuous with each other as well as with variable in size and contain multiple pH-sensitive hydro- the intermembrane space of the nuclear membrane. lases. These can degrade most biomolecules. 2 The cell membrane 1 Peroxisomes environment. However, the cell membrane also participates Peroxisomes are vesicular, ER-derived structures. They are in many important cellular processes, for example: smaller than lysosomes and contain different enzymes, • Maintenance of the resting membrane potential via primarily oxidative enzymes. They participate in the β-­ regulation of ion entry/exit. oxidation of fatty acids with very long chains (see Chapter 7) • Interaction with the intracellular cytoskeleton. and in the pentose phosphate pathway (see Chapter 5). • Transport of ions, metabolites and nutrients. Peroxisomal catalase also detoxifies reactive oxygen species • Cell adhesion to external structural elements within the such as hydrogen peroxide. surrounding tissue or to neighbouring cells. Cell membranes are impermeable to most molecules, how- Ribosomes ever specialized membrane-spanning transport proteins Eukaryotic cells contain 80S ribosomes, composed of a permit selective permeability to specific ions/molecules. small 40S and a large 60S subunit. They are composed of Structural and functional modification of these proteins al- rRNA and are manufactured in the nucleus. The two sub- lows regulation of entry and exit of the relevant transported units unite immediately prior to beginning translation (see molecule. Chapter 9). Ribosomes translate information contained in the mRNA into polypeptides by assembling peptides from Membrane components amino acids in the order dictated by the mRNA sequence. Ribosomes within the cytoplasm typically synthesize cy- Cell membranes are composed of a phospholipid bilayer toplasmic proteins, whereas those producing proteins des- studded with membrane proteins and cholesterol (Fig. 1.3). tined for the plasma membrane or vesicles associate with the rough ER. Phospholipids Phospholipids consist of a hydrophilic ‘head’, containing phosphate, and a hydrophobic fatty acid ‘tail’ of varying length and saturation. The amphiphilic nature of the mol- THE CELL MEMBRANE ecule means that phospholipids spontaneously adopt a bi- layer structure. The hydrophilic ‘heads’ form the surfaces of The cell membrane (Fig. 1.2) is a biological barrier that sep- the membrane, and the hydrophobic ‘tails’ interact with each arates the cellular interior from the external environment. other, forming the interior of the bilayer. In this way, the hy- The main function of the cell membrane is to separate the drophilic components are in contact with the intracellular cell from its surroundings and provide a distinct ­intracellular and extracellular environments. Properties Functions Microfilaments Pair of helically intertwined protofilaments