Biochemistry can be defined as the science concerned with the chemical basis of life (Greek bios means ‘life’). The cell is the structural unit of living systems. Thus, biochemistry can also be described as the science concerned with chemical constituents of living cells and with the reactions and processes they undergo. By this definition, biochemistry encompasses large areas of cell biology, of molecular biology and of molecular genetics.
CELL
The cell is the structural and functional unit of life. It is also known as the basic unit of biological activity.
Prokaryotic and Eukaryotic Cell
Present-day living organisms can be divided into two large groups, i.e the prokaryotes and eukaryotes. The prokaryotes are represented by bacteria (eubacteria and archaebacteria). These organisms do not possess a well-defined nucleus.
The eukaryotes include fungi, plants and animals, and comprise both unicellular and multicellular organisms. Multicellular eukaryotes are made up of a wide variety of cell types that are specialized for different tasks. A comparison of characteristics between prokaryotes and eukaryotes are listed in Table 1.1.
Structure of an Animal Cell
In the human body alone, there are at least 200 different cell types. The basic structures of an animal cell are as shown in the Figure 1.1.
The eukaryotic cell is subdivided by membranes. On the outside, it is enclosed by a plasma membrane. Inside the cell, there is a large space containing numerous components in solution—the cytoplasm. Different organelles are distributed in the cytoplasm.
The largest organelle is the nucleus. It is surrounded by a double membrane nuclear envelope. The endoplasmic reticulum (ER) is a closed network of shallow sacs and tubules, and is linked with the outer membrane of the nucleus. Another membrane bound organelle is the Golgi apparatus, which resembles a bundle of layered slices. The endosomes and exosomes are bubble-shaped compartments (vesicles) that are involved in the exchange of substances between the cell and its surroundings. Probably the most important organelles in the cell's metabolism are the mitochondria, which are around the same size as bacteria. The lysosomes and peroxisomes are small, globular organelles that carry out specific tasks. The whole cell is traversed by a framework of proteins known as the cytoskeleton.
Functions of Cellular Organelles
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Centrioles: Help to organize the assembly of microtubules.
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Chromosomes: House cellular deoxyribonucleic acid (DNA).
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Cilia and flagella: Aid in cellular locomotion.
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Endoplasmic reticulum: Synthesizes carbohydrates and lipids.
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Golgi complex: Manufactures, stores and ships certain cellular products.
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Lysosomes: Digest cellular macromolecules (hence they are called suicidal bags).
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Mitochondria: Provide energy for the cell.
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Nucleus: Controls cell growth and reproduction.
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Peroxisomes: Detoxify alcohol, form bile acid and use oxygen to breakdown fats.
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Ribosomes: Responsible for protein production via translation.
Cell Membrane
The plasma membrane is an envelope covering the cell. It separates and protects the cell from external environment. Besides being the protective barrier, it also provides a connecting system between the cell and environment.
Structure of Cell Membrane
The membrane is composed of lipids, proteins and carbohydrates. A lipid bilayer model for biological membrane was originally proposed in 1935 by Davson and Danielli. Later, the structure of the cell membrane was described as a fluid mosaic model by Singer and Nicolson in 1972 (Fig. 1.2).
The membrane consists of a bimolecular lipid layer with proteins inserted in it or bound to either surface. Integral membrane proteins are firmly embedded in the lipid layers. Some of these proteins completely span the bilayer called transmembrane proteins, while others are embedded in either the outer or inner leaflet of the lipid bilayer.
Loosely bound to the outer or inner surface of the membrane are the peripheral proteins. Many of the proteins and lipids have externally exposed oligosaccharide chains:
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Extrinsic (peripheral) membrane proteins are loosely held to the surface of the membrane and they can be easily separated, e.g. cytochrome of mitochondria.
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Intrinsic (integral) membrane proteins are tightly bound to lipid bilayer and they can be separated only by the use of detergents or organic solvents, e.g. hormone receptors and cytochrome P450.
LYSOSOMES
Lysosomes are tiny enzymes, which are considered as the bag of enzymes.
Enzymes Present
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Polysaccharide hydrolyzing enzymes (α-glucosidase, α-fucoside, β-galactosidase and hyaluronidase).
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Protein hydrolyzing enzymes (cathepsins, collagenase, elastase).
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Nucleic acid hydrolyzing enzymes (ribonuclease and deoxyribonuclease).
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Lipid hydrolyzing enzymes (fatty acyl esterase and phosphor lipases).
Clinical Correlation of Lysosomes
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In gout, urate crystals are deposited around knee joints. These crystals are easily phagocytosed, causing physical damage to lysosomes and release of enzymes.
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Following cell death, lysosomes rupture releasing the hydrolytic enzymes.
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Lysosomal proteases, cathepsins are implicated in tumor metastasis. Cathepsins, which are normally restricted to interior of lysosomes degrade basal lamina by hydrolyzing collagen and elastin so that other tumor cells can travel to form distant metastasis.
PEROXISOMES
Peroxisomes are also called microbodies, are single membrane cellular organelles.
Enzymes Present
Catalases and peroxidases are the enzymes present in peroxisomes, which will destroy the unwanted peroxides and radicals.
Clinical Correlation of Peroxisomes
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Deficiency of peroxisomal proteins can lead to adrenoleukodystrophy (ALD) or Brown-Schilder's disease characterized by progressive degeneration of liver, kidneys and brain.
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In Zellweger syndrome, proteins are not transported into peroxisomes leading to formation of empty peroxisomes or peroxisomal ghosts.
MITOCHONDRIA
Mitochondria are enclosed by two membranes—a smooth outer membrane and a markedly folded or tubular inner mitochondrial membrane, which has a large surface and encloses the matrix space. The folds of the inner membrane are known as cristae and tube-like protrusions are called tubules. The intermembrane space is located between the inner and the outer membranes.
Functions
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Mitochondria are also described as being the cell's biochemical powerhouse, since through oxidative phosphorylation (refer page 69), they produce the majority of cellular adenosine triphosphate (ATP).
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Pyruvate dehydrogenase (PDH), the tricarboxylic acid cycle, β-oxidation of fatty acids and parts of the urea cycle are located in the matrix. The respiratory chain, ATP synthesis and enzymes involved in heme biosynthesis are associated with the inner membrane.
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In addition to the endoplasmic reticulum, the mitochondria also function as an intracellular calcium reservoir. The mitochondria also plays an important role in ‘programmed cell death’—apoptosis.
MARKER MOLECULES
Marker molecules are molecules that occur exclusively or predominantly in one type of organelle (Table 1.2). The activity of organelle-specific enzymes (marker enzymes) is often assessed. The distribution of marker enzymes in the cell reflects the compartmentation of the processes they catalyze.
TRANSPORT MECHANISMS
Many small uncharged molecules pass freely through the lipid bilayer. Charged molecules, larger uncharged molecules and some small uncharged molecules are transferred through channels or pores, or by specific carrier proteins. 6The transport mechanisms (Fig. 1.3) are classified into:
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Passive transport: Transport of molecules in accordance with concentration gradient:
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Simple diffusion.
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Facilitated diffusion.
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Ion channels.
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Active transport.
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Passive Transport
Simple Diffusion
In order for molecules to simply diffuse across a membrane, they must either be quite small so as to enter membrane pores, go via the paracellular route or be soluble in the lipid membrane. No energy is required.
Facilitated Diffusion
Transport is facilitated by a transport protein therefore this is a carrier-mediated transport. The driving force is the concentration gradient. Glucose and amino acids use this mechanism.
Aquaporins
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Water channels that serve as selective pores through which water crosses plasma membrane of cells.
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Form tetramers in cell membrane.
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Facilitate transport of water and hence, control water content of cells.
Clinical correlation
Channelopathies are disorders due to abnormalities in proteins forming ion pores or channels. For example:
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Cystic fibrosis (chloride channels)
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Liddle's syndrome (sodium channels).
Ion Channels
Ion channels are transmembrane proteins that allow the selective entry of various ions. Selective ion-conductive pores are selective for one particular ion. Channels generally remain closed and they open in response to stimuli. The regulation is done by gated channels such as ligand-gated ion channel and calcium channel. For example:
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Nerve impulse propagation
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Synaptic transmission
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Secretion of active substances from cell.
Ionophores
Ionophores are membrane shuttles for specific ions, which transport certain ions. There are two types of ionophores:
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Mobile ion carriers (e.g. valinomycin)
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Channel formers (e.g. gramicidin).
Clinical correlation
Valinomycin allows potassium to permeate mitochondria and so it dissipates the proton gradient. Hence, it acts as an uncoupler of electron transport chain.
Active Transport
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Require 40% of total energy used
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Unidirectional
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Need special integral protein, called transporter protein
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System is saturated at high concentration of solutes
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Susceptible for inhibition by specific organic or inorganic compounds. For example, sodium-potassium pump (Na+ -K+ ATPase) cell has less concentration of sodium and high concentration of potassium (K). This is maintained by pump and the pump is activated by ATPase enzyme. They have binding sites for ATP and Na+ on inner side and K+ on outer side.
TRANSPORT SYSTEMS
Carrier is a transport protein that binds ions and other molecules and then changes their configuration, thus moving the bound molecule from one side of cell membrane to other.
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Types
There are two types of transport system.
Uniport
Uniport-carries single solute across the membrane (e.g. glucose transporter in most cells).
Cotransport
Cotransport is of two types—symport and antiport (Table 1.3).