Textbook of Medical Biochemistry MN Chatterjea, Rana Shinde
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1Cell Biology
  1. Cell and Cell Organelles: Chemistry and Functions
  2. Biological Membranes: Structure and Function
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CELL AND CELL ORGANELLES: CHEMISTRY AND FUNCTIONSCHAPTER 1

All organisms are built from cells. All animal tissues including human are also organised from collections of cells. Thus cell is the fundamental unit of life. If cell dies, tissue dies and it cannot function.
Modern cell theory can be divided into the following fundamental statements:
  • Cells make up all living matter
  • All cells arise from other cells
  • The genetic information required during the maintenance of existing cells and the production of new cells passes from one generation to the other next generation
  • The chemical reactions of an organism that is its metabolism, both anabolism and catabolism, takes place in the cells.
 
 
 
Types of Cells
In general two types of cells exist in nature. They are:
  1. Prokaryotic cells
  2. Eukaryotic cells
1. Prokaryotic Cells
Typical prokaryotic cells (Greek: Pro- before and karyon- nucleus) include the bacteria and cyanobacteria. Most studied prokaryotic cell is Escherichia coli (E. coli).
Characteristics
  • It has a minimum of internal organisation and smaller in size
  • It does not have any membrane bound organelles.
  • Its genetic material is not enclosed by a nuclear membrane
  • Its DNA is not complexed with histones. Histones are not found in prokaryotic cells
  • Its respiratory system is closely associated with its plasma membrane and
  • Its sexual reproduction does not involve mitosis or meiosis.
2. Eukaryotic Cells
The eukaryotic cells (Greek: Eu-true and karyon-nucleus) include the protists, fungi, plants and animals including humans. Cells are larger in size (Fig. 1.1).
Characteristics
  • It has considerable degree of internal structure with a large number of distinctive membrane enclosed having specific functions
  • Nucleus is the site for informational components collectively called chromatin
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    zoom view
    Fig. 1.1: Schematic representation of an eukaryotic cell with cell organelles
  • Sexual reproduction involves both mitosis and meiosis
  • The respiratory site is the mitochondria
  • In the plant cells, the site of the conversion of radiant energy to chemical energy is the highly structural chloroplasts.
Essential differences of prokaryotic and eukaryotic cells are given in Table 1.1
Table 1.1   Essential differences between prokaryotic and eukaryotic cell
Prokaryotic cell
Eukaryotic cell
1. Smaller in size 1 to 10 μm
1. Larger in size 10 to 100 μm or more
2. Mainly unicellular
2. Mainly multicellular (with few exceptions). Several different types present
3. Single membrane, surrounded by rigid cell wall
3. Lipid bilayer membrane with proteins
4. Anaerobic or aerobic
4. Aerobic
5. Not well defined nucleus, only a nuclear zone with DNA
Histones absent
5. Nucleus well defined, 4 to 6 μm in diameter, contains DNA and surrounded by a perinuclear membrane
Histones present
6. No nuclei
6. Nucleolus present, rich in RNA
7. Cytoplasm contains no cell organelles
7. Membrane bound cell organelles are present
8. Ribosomes present free in cytoplasm
8. Ribosomes studded on outer surface of endoplasmic reticulum present
9. Mitochondria absent. Enzymes of energy metabolism bound to membrane
9. Mitochondria present Power house of the cell. Enzymes of energy metabolism are located in mitochondria
10. Golgi apparatus absent. Storage granules with polysaccharides
10. Golgi apparatus present—flattened single membrane vesicles
11. Lysosomes—absent
11. Lysosomes present—single membrane vesicle containing packets of hydrolytic enzymes
12. Cell division usually by fission, no mitosis
12. Cell division—by mitosis
13. Cytoskeleton—absent
13. Cytoskeleton—present
14. RNA and protein synthesis in same compartment
14. RNA synthesised and processed in nucleus. Proteins synthesised in cytoplasm
15. Examples are bacteria, cyanobacteria, rickettsia
15. Examples: Protists, fungi, plants and animal cells
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A. Cell Organelles
Eukaryotic cells contain many membrane-bound organelles that carryout specific cellular processes. Chief organelles and their functions are as follows:
1. Nucleus: The nucleus contains more than 95 per cent of the cell's DNA and is the control centre of the eukaryotic cell.
  • Nuclear envelope: A double membrane structure called the nuclear envelope separates the nucleus from the cytosol.
  • Nuclear pore complexes: These are embedded in the nuclear envelope. These complex structures control the movement of proteins and the nucleic acid ribonucleic acids (RNAs) across the nuclear envelope.
  • Chromatin: DNA in the nucleus is coiled into a dense mass called chromatin, so named because it is stained darkly with certain dyes.
  • Nucleolus: A second dense mass closely associated with the inner nuclear envelope is called nucleolus.
  • Nucleoplasm: Nucleoplasm of nucleus contain various enzymes such as DNA polymerases, and RNA polymerases, for m-RNA and t-RNA synthe-sis.
Functions
  • DNA replication and RNA transcription of DNA occur in the nucleus. Transcription is the first step in the expression of genetic information and is the major metabolic activity of the nucleus.
  • The nucleolus is nonmembranous and contains RNA polymerase, RNAase, ATPase and other enzymes but no DNA polymerase. Nucleolus is the site of synthesis of ribosomal RNA (r-RNA).
  • Nucleolus is also the major site where ribosome subunits are assembled.
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Fig. 1.2A: A mitochondrion—shows half split to show the inner membrane with cristae
2. Mitochondrion: Mitochondrion is the power house of cell (Figs 1.2A and B).
  • Number: The number of mitochondria in a cell varies dramatically. Some algae contain only one mitochondrion, whereas the protozoan Chaos contain half a million. A mammalian liver cell contains from 800 to 2500 mitochondria.
  • Size: They vary greatly in size. A typical mammalian mitochondrion has a diameter of 0.2 to 0.8µ and a length of 0.5 to 1.0µm.
  • Shape: The shape of mitochondrion is not static. Mitochondria assume many different shapes under different metabolic conditions.
Structure and Functions
The mitochondrion is bounded by two concentric membranes that have markedly different properties and biological functions.
 
Mitochondrial Membranes
(a) Outer mitochondrial membrane: The outer mitochondrial membrane consists mostly of phospholipids and contains a considerable amount of cholesterol. The outer membrane also contains many copies of the protein called Porin.
Functions of Porin and other Proteins
  1. These proteins form channels that permit substances with molecular weights of less than < 10,000 to diffuse freely across the outer mitochondrial membrane.
  2. Other proteins in the outer membrane carry out various reactions in fatty acid and phospholipid biosynthesis and are responsible for some oxidation reactions.
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Fig. 1.2B: Cross-section of a mitochondrion—showing various layers and cristae
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(b) Inner mitochondrial membrane: The inner mitochondrial membrane is very rich in proteins and the ratio of lipid to proteins is only 0.27:1 by weight. It contains high proportion of the phospholipid cardiolipin. In contrast to outer membrane, the inner membrane is virtually impermeable to polar and ionic substances. These substances enter the mitochondrion only through the mediation of specific transport proteins.
  • Cristae: The inner mitochondrial membrane is highly folded. The tightly packed inward folds are called “cristae”.
Functional changes: It is now known that mitochondria undergo dramatic changes when they switch over from resting state to a respiring state. In the respiring state, the inner membrane is not folded into cristae, rather it seems to shrink leaving a much more voluminous inter membrane space.
(c) Intermembrane space: The space between the outer and inner membranes is known as the intermembrane space. Since the outer membrane is freely permeable to small molecules, the intermembrane space has about the same ionic composition as the cytosol.
(d) Mitochondrial matrix: The region enclosed by the inner membrane is known as the mitochondrial matrix.
Composition of matrix: The enzymes responsible for citric acid cycle and fatty acid oxidation are located in the matrix. The matrix also contains several strands of circular DNA, ribosomes and enzymes required for the biosynthesis of the proteins coded in the mitochondrial genome. The mitochondrion is not, however, genetically autonomous, and the genes encoding most mitochondrial proteins are present in nuclear DNA.
Functions
  • Many enzymes associated with carbohydrates, fatty acids and nitrogen metabolism are located within the mitochondrion. Enzymes of electron transport and oxidative phosphorylation are also located in different areas of this cell organelle.
    Table 1.2 gives the names of some of the important enzymes and their location.
  • The mitochondrion is specialised for the rapid oxidation of NADH (reduced NAD) and FAD. H2 (reduced FAD) produced in the reactions of glycolysis, the citric acid cycle and the oxidation of fatty acids. The energy produced is trapped and stored as ATP, for future use of energy in the body.
3. Endoplasmic reticulum (ER): Eukaryotic cells are characterised by several membrane complexes that are interconnected by separate organelles. These organelles are involved in protein synthesis, transport, modification, storage and secretion.
Varying in shape, size and amount, the endoplasmic reticulum (ER) extends from the cell membrane, coats the nucleus, surrounds the mitochondria and appears to connect directly to the Golgi apparatus. These membranes and the aqueous channels they enclose are called cisternae.
Table 1.2   Location of some of the important enzymes in mitochondrion
Outer membrane
Intermediate space
Inner membrane
Matrix
• Cytochrome b5
• Adenylate kinase
• Cytochromes b, C1, C, a and a3
• Pyruvate dehydrogenase complex (PDH)
• Cytochrome b5 reductase
• Sulphite oxidase
• NADH dehydrogenase
• Citrate synthase
• Fatty acid CoA synthetase
• Nucleoside diphospho-kinase
• Succinate dehydrogenase
• Aconitase
• FA elongation system
• Ubiquinone
• Isocitrate dehydrogenase (ICD)
• Phospholipase A
• Electron-transferring flavoproteins (ETF)
• α-oxoglutarate dehydrogenase
• Malate dehydrogenase
• Nucleoside diphosphokinase
• Vector ATP synthase (F0F1)
• FA oxidation system
• β-OH-butyrate dehydrogenase
• Ornithine transcarbamoylase
• Carnitine palmityl transferases
• Carbamoyl phosphate synthetase I
• All translocases
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Types: There are two kinds of endoplasmic reticulum (ER):
  1. Rough surfaced ER, also known as ergastoplasm. They are coated with ribosomes. Near the nucleus, this type of ER merges with the outer membrane of the nuclear envelope.
  2. Smooth surfaced ER: They do not have attached ribosomes.
Functions
  1. Function of rough ER: Rough ER synthesises membrane lipids, and secretory proteins. These proteins are inserted through the ER membrane into the lumen of the cisternae where they are modified and transported through the cell.
  2. Function of smooth ER: Smooth endoplasmic reticulum is involved:
    1. In lipid synthesis and
    2. Modification and transport of proteins synthesised in the rough ER
Note: A number of important enzymes are associated with the endoplasmic reticulum of mammalian liver cells. These include the enzymes responsible for the synthesis of sterol, triacylglycerol (TG), Phospholipids (PL) and the enzymes involved in detoxification of drugs. Cytochrome P450 which participates in drug hydroxylation reside in the ER.
4. Golgi complexes (or Golgi apparatus): They are also called Dictyosomes. Each eukaryotic cell contains a unique stack of smooth surfaced compartments or cisternae that make up the Golgi complex. The ER is usually closely associated with the Golgi complexes, which contain flattened, fluid filled golgi sacs.
The Golgi complex has a Proximal or Cis compartment, a medial compartment and a distal or trans compartment.
Recent evidence suggests strongly that the complex serves as a unique sorting device that receives newly synthesized proteins, all containing signal or transit peptides from the ER. It is interesting to note that those proteins with no signal or transit peptides regions are rejected by the Golgi apparatus without processing it further and remain as cytoplasmic protein.
Functions
  1. On the proximal or cis side, the Golgi complexes receive the newly synthesised proteins by ER via transfer vesicles.
  2. The post-translational modifications take place in the golgi lumen (median part) where the carbo hydrates and lipid precursors are added to proteins to form glycoproteins and lipoproteins respectively.
  3. On the distal or trans side they release proteins via modified membranes called secretory vesicles. These secretory vesicles move to and fuse with the plasma membrane where the contents may be expelled by a process called exocytosis.
5. Lysosomes: Lysosomes are cell organelles found in cells which contain packet of enzymes. Lysosome word derived from Greek word Gree, meaning lysis (loosening). Discovered and described for the first time as a new organelle by the Belgian Biochemist de Duve in 1955.
  • Size: Mean diameter is approximately 0.4µ (varies in between that of microsomes and mitochondria). They are surrounded by a lipoprotein membrane.
  • Lysosomes are found in all animal cells, except erythrocytes, in varying numbers and types.
  • pH: pH inside the lysosomes is lower than that of cytosol. The lysosomal enzymes have an optimal pH around 5. Acid phosphatase is used as a marker enzyme for this organelle.
Enzyme Groups Present in Lysosomes
Essentially the enzymes about 30 to 40, are hydrolytic in nature. They can be grouped as follows:
Lysosomal Enzymes
1. Proteolytic enzymes
• Cathepsins (Proteinase)
• Collagenase
• Elastase
2. Nucleic acid hydrolysing enzymes
• Ribonucleases
• Deoxyribonucleases
3. Lipid hydrolysing enzymes
• Lipases
• Phospholipases
• Fatty acyl esterases
4. Carbohydrate splitting enzymes
• ɑ-glucosidase
• β-galactosidase
• Hyaluronidase
• Aryl sulphatase, etc.
5. Other enzymes
• Acid phosphatase
• Catalase, etc.
  • As long as the lysosomal membrane is intact, the encapsulated enzymes can act only locally. But when the membrane is ruptured, the enzymes are released into the cytoplasm and can hydrolyse external substrates (biopolymers).
6. Peroxisomes: Peroxisomes are small organelles also called Microbodies, present in eukaryotic cell. The particles are approximately 0.5µ in diameter. These subcellular respiratory organelles have no energy-coupled electron transport systems and are probably formed by budding from smooth endoplasmic reticulum (ER).
Functions
  1. They carryout oxidation reactions in which toxic hydrogen peroxide (H2O2) is produced, which is destroyed by the enzyme catalase.
  2. Recently it has been shown that liver peroxisomes have an unusually active β-oxidative system capable of oxidising long chain fatty acids (C 16 to 18 or > C 18)
The β-oxidation enzymes of peroxisomes are rather unique in that the first step of the oxidation is catalysed by a flavoprotein, an “acyl Co-A oxidase”
zoom view
H2O2 produced is destroyed by catalase.
Peroxisomes may be absent in inherited disorder Zellweger's syndrome(Refer to Chapter on fatty acid oxidation).
7. Cytoskeleton: For many years, biochemists have considered the cytosol a compartment containing soluble enzymes, metabolites and salts in an aqueous but gel like environment.
Studies now support the idea that this compartment contains actually a complex network of fine structures called (a) microtubules, (b) microfilaments and (c) microtrabeculae.
(a) Microtubules: They are long unbranched slender cylindrical structures with an average diameter of about 25 nm. The structures are made primarily by the self-assembly of the heterodimer, tubulin having molecular weight 50,000.
Functions
  • An important function of microtubules is their role in the assembly and disassembly of the spindle structures during mitosis.
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  • They also provide internal structure to the cell and helps in maintenance of shape of the eukaryotic cell.
  • As they seem to associate with the inner face of plasma membrane, they may be involved in transmembrane signals.
(b) Microfilaments: They are more slender cylinder like structures made up of the contractile protein actin. They are linked to the inner face of the plasma membrane.
Functions
These structures may be involved in the generation of forces for internal cell motion.
(c) Microtrabeculae: They appear to be very fragile tubes that form a transient network in the cytosol.
Functions
It is not yet clearly understood and established fully whether or not soluble enzymes are associated or clustered with these structures to form unstable multienzyme complexes.
 
B. Cytoplasm (Cytosol)
This is the simplest structure of the cell. Organelles free sap is called as cytosol. Many metabolic reactions take place in cytosol where substrates and cofactors interact with various enzymes. There is no specific structure for cytosol. It has a high protein contents. The actual physiochemical state of cytosol is poorly understood. A major role of cytosol is to support synthesis of proteins on the rough endoplasmic reticulum by supplying cofactors and energy.
Cytosol also contains free ribosomes often in the polysome form. They contain many different types of proteins and ribosomal RNA or r-RNA. They exist as 2 subunits and act as the site of protein synthesis.