Textbook of Biochemistry for Medical Students First Edition: Second Edition: Third Edition: Fourth Edition: Fifth Edition: Sixth Edition. —Mata Amritanandamayi Devi Preface to the Sixth Edition We are glad to present the sixth edition of the Textbook of Biochemistry for Medical Students. With this. PDF | On Dec 1, , Vishnu Kumar and others published TEXT basic textbook for the undergraduate student, it has. resource material for postgraduates and advanced. learners in biochemistry, medicine and para medical.
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In retrospect, it gives immense satisfaction to note that this book served the students and faculty for the past two decades. We are bringing out the new edition of the textbook every 3 years. A major addition of this edition is the incorporation of clinical case studies in almost all chapters.
We hope that this feature will help the students to identify the clinical relevance of the biochemistry. Further, chapters on clinical chemistry have been extensively updated and clinically relevant points were further added. Rapid progress has been made in the area of molecular biology during past few years, and these advances are to be reflected in this book also.
The major change in this Seventh edition is that advanced knowledge has been added in almost all chapters, clinical case studies have been added in relevant chapters; and a few new chapters were added. The print fonts and font size have also been changed for better readability. From the First edition onwards, our policy was to provide not only basic essentials but also some of the advanced knowledge.
A lot of students have appreciated this approach, as it helped them to pass the postgraduate PG entrance examinations at a later stage. However, this asset has paved the way for a general criticism that the extra details are a burden to the average students. Especially, when read for the first time, the student may find it difficult to sort out the essential minimum from the desirable bulk. In this Seventh edition, advanced topics are given in small prints. In essence, this book is composed of three complementary books.
The bold printed areas will be useful for the student at the time of revision just before the examinations; regular printed pages are meant for an average first year MBBS student and the fine printed paragraphs are targeted to the advanced students preparing for the PG entrance. Essay questions, short notes, multiple choice questions and viva voce type questions are given as a separate book, but free of cost. These questions are compiled from the question papers of various universities during the last decade.
These questions will be ideal for students for last-minute preparation for examinations. We are introducing the online study material, which provides concepts of major topic as well as clinical case studies. This shall be updated through the year. Hence, students are advised to check the web page at regular intervals. A textbook will be matured only by successive revisions. In the preface for the First edition, we expressed our desire to revise the textbook every 3 years.
We were fortunate to keep that promise. This book has undergone metamorphosis during each edition. Chemical structures with computer technology were introduced in the Second edition. The free radicals damage molecules, cell membranes, tissues and genes. Chapter Catalase and peroxidase are the enzymes present in peroxisomes which will destroy the unwanted peroxides and other free radicals.
Clinical applications of peroxisomes are shown in Box 2. They are spherical, oval or rod-like bodies, about 0.
Clinical Applications of Lysosomes 1. In gout, urate crystals are deposited around knee joints Chapter These crystals when phagocytosed, cause physical damage to lysosomes and release of enzymes. Inflammation and arthritis result. Following cell death, the lysosomes rupture releasing the hydrolytic enzymes which bring about postmortem autolysis.
Lysosomal proteases, cathepsins are implicated in tumor metastasis. Cathepsins are normally restricted to the interior of lysosomes, but certain cancer cells liberate the cathepsins out of the cells. Then cathepsins degrade the basal lamina by hydrolysing collagen and elastin, so that other tumor cells can travel out to form distant metastasis. There are a few genetic diseases, where lysosomal enzymes are deficient or absent.
This leads to accumulation of lipids or polysaccharides Chapters 10 and Silicosis results from inhalation of silica particles into the lungs which are taken up by phagocytes.
Lysosomal membrane ruptures, releasing the enzymes. This stimulates fibroblast to proliferate and deposit collagen fibers, resulting in fibrosis and decreased lungs elasticity. Inclusion cell I- cell disease is a rare condition in which lysosomes lack in enzymes, but they are seen in blood. This means that the enzymes are synthesized, but are not able to reach the correct site. It is shown that mannose-6phosphate is the marker to target the nascent enzymes to lysosomes.
In these persons, the carbohydrate units are not added to the enzyme. Mannosephosphatedeficient enzymes cannot reach their destination protein targetting defect. The synthesized materials may be collected into lysosome packets. Discovered in by Rene de Duve Nobel prize , lysosomes are tiny organelles. Solid wastes of a township are usually decomposed in incinerators.
Inside a cell, such a process is taking place within the lysosomes.
They are bags of enzymes. Clinical applications of lysosomes are shown in Box 2. Endocytic vesicles and phagosomes are fused with lysosome primary to form the secondary lysosome or digestive vacuole.
Foreign particles are progressively digested inside these vacuoles. Completely hydrolysed products are utilized by the cell. As long as the lysosomal membrane is intact, the encapsulated enzymes can act only locally. But when the membrane is disrupted, the released enzymes can hydrolyse external substrates, leading to tissue damage. The lysosomal enzymes have an optimum pH around 5. These enzymes are a. Polysaccharide hydrolysing enzymes alpha-glucosidase, alpha-fucosidase, beta-galactosidase, alphamannosidase, beta-glucuronidase, hyaluronidase, aryl sulfatase, lysozyme b Protein hydrolysing enzymes cathepsins, collagenase, elastase, peptidases c.
Nucleic acid hydrolysing enzymes ribonuclease, deoxyribonuclease. Mitochondria Fig. Erythrocytes do not contain mitochondria. The tail of spermatozoa is fully packed with mitochondria.
Mitochondria are the powerhouse of the cell, where energy released from oxidation of food stuffs is trapped as chemical energy in the form of ATP Chapter Metabolic functions of mitochondria are shown in Table 2.
Mitochondria have two membranes. The inner membrane convolutes into folds or cristae Fig. The inner mitochondrial membrane contains the enzymes of electron transport chain Chapter The fluid matrix contains the enzymes of citric acid cycle, urea cycle and heme synthesis. Cytochrome P system present in mitochondrial inner membrane is involved in steroidogenesis Chapter Superoxide dismutase is present in cytosol and mitochondria Chapter Box 2. Peroxisomal Deficiency Diseases 1. Deficiency of peroxisomal matrix proteins can lead to adreno leuko dystrophy ALD Brown-Schilders disease characterized by progressive degeneration of liver, kidney and brain.
It is a rare autosomal recessive condition. In Zellweger syndrome, proteins are not transported into the peroxisomes. This leads to formation of empty peroxisomes or peroxisomal ghosts inside the cells.
Protein targetting defects are described in Chapter Primary hyperoxaluria is due to the defective peroxisomal metabolism of glyoxalate derived from glycine Chapter Proteins are anchored in the membrane by different mechanisms 5.
Mitochondria also contain specific DNA. The integral inner membrane proteins, are made by mitochondrial protein synthesising machinery. However the majority of proteins, especially of outer membrane are synthesised under the control of cellular DNA.
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The division of mitochondria is under the command of mitochondrial DNA. Mitochondrial ribosomes are different from cellular ribosomes.
Antibiotics inhibiting bacterial protein synthesis do not affect cellular processes, but do inhibit mitochondrial protein biosynthesis Chapter Taking into consideration such evidences, it is assumed that mitochondria are parasites which entered into cells at a time when multicellular organisms were being evolved.
These parasites provided energy in large quantities giving an evolutionary advantage to the cell; the cell gave protection to these parasites.
This perfect symbiosis, in turn, evolved into a cellular organelle of mitochondria. A summary of functions of organelles is given in Table 2.
Comparison of Cell with a Factory Plasma membrane Nucleus Endoreticulum Golgi apparatus Lysosomes Vacuoles Mitochondria Fence with gates; gates open when message is received Managers office Conveyer belt of production units Packing units Incinerators Lorries carrying finished products.
The lipid bilayer shows free lateral movement of its components, hence the membrane is said to be fluid in nature. Fluidity enables the membrane to perform endocytosis and exocytosis. However, the components do not freely move from inner to outer layer, or outer to inner layer flip-flop movement is restricted.
During apoptosis programmed cell death , flip-flop movement occurs. This Flip-flop movement is catalyzed by enzymes.
Flippases catalyse the transfer of amino phospholipids across the membrane. Floppases catalyse the outward directed movement which is ATP dependent. This is mainly seen in the role of ABC proteins mediating the efflux of cholesterol and the extrusion of drugs from cells. The MDR multi drug resistance associated p-glycoprotein is a floppase. Ernst Ruska designed the first electron microscope in Gerd Binning and Heinrich Rohrer introduced the scanning electron microscopy in by which the outer and inner layers of membranes could be visualized separately.
All the three workers were awarded Nobel prize in The plasma membrane separates the cell from the external environment.
It has highly selective permeability properties so that the entry and exit of compounds are regulated. The cellular metabolism is in turn influenced and probably regulated by the membrane. The membrane is metabolically very active. The enzyme, nucleotide phosphatase 5' nucleotidase and alkaline phosphatase are seen on the outer part of cell membrane; they are therefore called ecto-enzymes.
Membranes are mainly made up of lipids, proteins and small amount of carbohydrates. The contents of these compounds vary according to the nature of the membrane. The carbohydrates are present as glycoproteins and glycolipids. Phospholipids are the most common lipids present and they are amphipathic in nature.
Cell membranes also contain cholesterol. Later, the structure of the biomembranes was described as a fluid mosaic model Singer and Nicolson, The phospholipids are arranged in bilayers with the polar head groups oriented towards the extracellular side and the cytoplasmic side with a hydrophobic core Fig. The distribution of the phospholipids is such that choline containing phospholipids are mainly in the external layer and ethanolamine and serine containing phospholipids in the inner layer.
Each leaflet is 25 thick, with the head portion 10 and tail 15 thick. The total thickness is about 50 to The cholesterol content of the membrane alters the fluidity of the membrane. When cholesterol concentration increases, the membrane becomes less fluid on the outer surface, but more fluid in the hydrophobic core. The effect of cholesterol on membrane fluidity is different at different temperatures.
At temperature below the Tm cholesterol increases fluidity and there by permeability of the membrane. At temperatures above the Tm, cholesterol decreases fluidity. In spur cell anemia and alcoholic cirrhosis membrane studies have revealed the role of excess cholesterol.
The decrease in membrane fluidity may affect the activities of receptors and ion channels. Fluidity of cellular membranes responds to variations in diet and physiological states. Increased release of reactive oxygen species ROS , increase in cytosolic calcium and lipid peroxidation have been found to adversely affect membrane fluidity.
Anesthetics may act by changing membrane fluidity. The nature of the fatty acids also affects the fluidity of the membrane, the more unsaturated cis fatty acids increase the fluidity.
The fluidity of the membrane is maintained by the length of the hydrocarbon chain, degree of unsaturation and nature of the polar head groups. Trans fatty acids TFA decrease the fluidity of membranes due to close packing of hydrocarbon chains. Cis double bonds create a kink in the hydrocarbon chain and have a marked effect on fluidity.
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Second OH group of. Chemical Basis of Life glycerol in membrane phospholipids is often esterified to an unsaturated fatty acid, mono unsaturated oleic or polyunsaturated linoleic, linolenic or arachidonic. The nature of fatty acids and cholesterol content varies depending on diet. A higher proportion of PUFA which increases the fluidity favors the binding of insulin to its receptor, a trans membrane protein.
The endocytosis of cholesterol containing lipoproteins may be caveolae mediated. Similarly the fusion and budding of viral particles are also mediated by caveolae.
Membrane Proteins 5-A. The peripheral proteins exist on the surfaces of the bilayer Fig. They are attached by ionic and polar bonds to polar heads of the lipids. Anchoring of proteins to lipid bilayers: Several peripheral membrane proteins are tethered to the membranes by covalent linkage with the membrane lipids. Since the lipids are inserted into the hydrophobic core, the proteins are firmly anchored. A typical form of linkage is the one involving phosphatidyl inositol which is attached to a glycan.
This glycan unit has ethanolamine, phosphate and several carbohydrate residues. This glycan chain includes a glucose covalently attached to the C terminus of a protein by the ethanolamine and to the phosphatidyl inositol by the glucosamine. The fatty acyl groups of the phosphatidyl inositol diphosphate PIP2 are firmly inserted into the lipid membrane thus anchoring the protein. This is referred to as glycosyl phosphatidyl inositol GPI anchor.
Microdomains on membranes: GPI anchored proteins are often attached to the external surface of plasma membrane at microdomains called lipid rafts. They are areas on the membrane having predominantly glycosphingolipids and cholesterol. The localization and activity of the protein can be regulated by anchoring and release.
Lipid rafts have a role in endocytosis, G protein signaling and binding of viral pathogens. The GPI anchors that tether proteins to the membrane are also seen at the lipid rafts.
Membrane proteins may be anchored by covalent bonding, palmitoylation and myrystoylation. Caveolae are flask shaped indentations on the areas of lipid rafts that are involved in membrane transport and signal transduction.
Caveolae contain the protein caveolin, along with other receptor proteins. Transport of macromolecules IgA from the luminal side occurs. The integral membrane proteins are deeply embedded in the bilayer and are attached by hydrophobic bonds or van der Waals forces.
Some of the integral membrane proteins span the whole bilayer and they are called transmembrane proteins Fig. The hydrophobic side chains of the amino acids are embedded in the hydrophobic central core of the membrane.
The transmembrane proteins can serve as receptors for hormones, growth factors, neurotransmitters , tissue specific antigens, ion channels, membrane-based enzymes, etc. Bacterial Cell Wall Prokaryotic bacterial cells as well as plant cells have a cell wall surrounding the plasma membrane; this cell wall provides mechanical strength to withstand high osmotic pressure. Animal cells are devoid of the cell wall; they have only plasma membrane.
Major constituent of bacterial cell wall is a heteropolysaccharide, consisting of repeating units of N-acetyl muramic acid NAM and N-acetyl glucosamine NAG. This polysaccharide provides mechanical strength to the plasma membrane. Synthesis of this complex polysaccharide is blocked by penicillin. This inhibition is responsible for the bactericidal action of penicillin. This tight junction permits calcium and other small molecules to pass through from one cell to another through narrow hydrophilic pores.
Some sort of communication between cells thus results. Absence of tight junction is implicated in loss of contact inhibition in cancer cells Chapter Tight junctions also seal off subepithelial spaces of organs from the lumen. They contain specialized proteins such as occludin, claudins and other adhesion molecules. Chapter 2; Subcellular Organelles and Cell Membranes 13 chromosomal movements during cell division.
The cytoskeleton is made up of a network of microtubules Fig. Tubules consist of polymers of tubulin. Molecular Motors Proteins that are responsible for co-ordinated movements in tissues and cells are referred to as molecular motors. These may be ATP driven as in the case of the contractile proteins; actin and myosin in muscle as well as dyenin and tubulin in cilia and flagella. Kinesin which mediates movement of vesicles on microtubules also requires ATP. Water channel or aquaporin Myelin Sheath It is made up of the membrane of Schwann cells Theodor Schwann, condensed and spiralled many times around the central axon.
The cytoplasm of Schwann cells is squeezed to one side of the cell. Myelin is composed of sphingomyelin, cholesterol and cerebroside. Myelin sheaths thin out in certain regions Node of Ranvier Anotoine Ranvier, Due to this arrangement, the propagation of nerve impulse is wavelike; and the speed of propagation is also increased.
Upon stimulation, there is rapid influx of sodium and calcium, so that depolarization occurs. Voltage gradient is quickly regained by ion pumps. The ions flow in and out of membrane only where membrane is free of insulation; hence the wave-like propagation of impulse. In multiple sclerosis, demyelination occurs at discrete areas, velocity of nerve impulse is reduced, leading to motor and sensory deficits. Microvilli Microvilli of intestinal epithelial cells and pseudopodia of macrophages are produced by membrane evagination.
This is due to the fluid nature of membranes. Membranes of Organelle Membranes of endoplasmic reticulum, nucleus, lysosomes and outer layer of mitochondria may be considered as variants of plasma membrane. Cytoskeleton Human body is supported by the skeletal system; similarly the structure of a cell is maintained by the cytoskeleton present underneath the plasma membrane.
The cytoskeleton is responsible for the shape of the cell, its motility and. Water soluble compounds are generally impermeable and require carrier mediated transport.
An important function of the membrane is to withhold unwanted molecules, while permitting entry of molecules necessary for cellular metabolism. Transport mechanisms are classified into 1. Passive transport 1-A. Simple diffusion 1-B. Facilitated diffusion. Ion channels are specialized carrier systems. They allow passage of molecules in accordance with the concentration gradient. Active transport 3. Pumps can drive molecules against the gradient using energy.
Simple Diffusion Solutes and gases enter into the cells passively. They are driven by the concentration gradient. The rate of entry is proportional to the solubility of that. Simple diffusion occurs from higher to lower concentration. This does not require any energy. However, it is a very slow process.
Facilitated Diffusion This is a carrier mediated process Fig. Important features of facilitated diffusion are: The carrier mechanism could be saturated which is similar to the Vmax of enzymes. Structurally similar solutes can competitively inhibit the entry of the solutes. Facilitated diffusion can operate bidirectionally. This mechanism does not require energy but the rate of transport is more rapid than simple diffusion process. The carrier molecules can exist in two conformations, Ping and Pong states.
In the pong. Then there is a conformational change. In the ping state, the active sites are facing the interior of the cell, where the concentration of the solute is minimal. This will cause the release of the solute molecules and the protein molecule reverts to the pong state. By this mechanism the inward flow is facilitated, but the outward flow is inhibited Fig. Hormones regulate the number of carrier molecules. For example, glucose transport across membrane is by facilitated diffusion involving a family of glucose transporters.
Glucose transport is described in detail in Chapter 9. Aquaporins They are water channels Fig. They are a family of membrane channel proteins that serve as selective pores through which water crosses the plasma membranes of cells. They form tetramers in the cell membrane, and facilitate the transport of water They control the water content of cells.
Agre and MacKinnon were awarded Nobel prize for chemistry in for their contributions on aquaporins and water channels. Diseases such as nephrogenic diabetes insipidus is due to impaired function of these channels.
Channelopathies are a group of disorders that result from abnormalities in the proteins forming the ion pores or channels. A few examples are cystic fibrosis chloride channel , Liddle's syndrome sodium channel and periodic paralysis potassium channel.
Ion Channels Membranes have special devices called ion channels Fig. Ion channels are transmembrane proteins that allow the selective entry of Box 2. Salient Features of Ion Channels 1. They are transmembrane proteins 2. Selective for one particular ion 3. Regulation of activity is done by voltage-gated, ligand-gated or mechanically gated mechanisms 4.
Transport through the channel is very quick. The sodium potassium pump It brings sodium ions out of the cells and potassium ions into the cells. This favors phosphorylation of the protein along with hydrolysis of ATP. Potassium binding leads to release of phosphate group. The cycle repeats. Types of transport mechanisms Carrier Against Energy Examples gradient required Simple diffusion Facilitated diffusion Primary active Secondary active Ion channels no yes yes yes yes no no yes yes no nil nil directly indirect no water glucose to RBCs sodium pump glucose to intestine sodium channel.
Clinical Applications of Channels 1. Sodium Channels: Local anesthetics such as procaine act on sodium channels both as blockers and on gating mechanisms to hold the channel in an inactivated state. Point mutation in sodium channel leads to myotonia, characterized by increased muscle excitability and contractility.
In Liddle's disease, the sodium channels in the renal epithelium are mutated, resulting in excessive sodium reabsorption, water retention and elevated blood pressure. Potassium channel mutations in "Long QT syndrome" leads to inherited cardiac arrythmia, where repolarization of the ventricle is delayed, resulting in prolonged QT intervals in ECG.
Chloride channels: The role of GABA and glycine as inhibitory neuro-transmitters is attributed to their ability to open the chloride channels at the postsynaptic membranes. Cystic fibrosis is due to certain mutations in the CFTR gene cystic fibrosis transmembrane regulator protein , which is a chloride transporter. The excitation of retinal rods by a photon is by closing of cation specific channels resulting in hyperpolarization of the rod cell membrane.
This light induced hyperpolarization is the major event in visual excitation see, Chapter Salient features are enumerated in Box 2. These are selective ion conductive pores. Ion channels are specialized protein molecules that span the membranes.
The channels generally remain closed, but in response to stimulus, they open allowing rapid flux of ions down the gradient.
This may be compared to opening of the gate of a cinema house, when people rush to enter in. Hence this regulation is named as "gated". Such ion channels are important for nerve impulse propagation, synaptic transmission and secretion of biologically active substances from the cells.
Ion channels are different from ion transport pumps described below. Ligand Gated Channels Ligand gated channels are opened by binding of effectors.
The binding of a ligand to a receptor site. Left side, voltaged gated channels; on the right side, ligand gated channels; closed and open positions. The ligand may be an extracellular signalling molecule or an intracellular messenger.
Clinical applications of channels are shown in Box 2. Acetyl choline receptor Fig. It is present in postsynaptic membrane. It is a complex of 5 subunits, consisting of acetyl choline binding site and the ion channel.
This generates an action potential in the postsynaptic nerve. The channel opens only for a millisecond, because the acetyl choline is rapidly degraded by acetyl cholinesterase. Calcium channels: Under appropriate stimuli calcium channels are opened in the sarcoplasmic reticulum membrane, leading to an elevated calcium level in the cytosol of muscle cells. Calcium channel blockers are therefore widely used in the management of hypertension. Amelogenin, a protein present in enamel of teeth has hydrophobic residues on the outside.
A 27 amino acid portion of amelogenin functions as a calcium channel. Chemical Basis of Life Phosphorylation of a serine residue of the protein opens the calcium channel, through which calcium ions zoom through and are funnelled to the mineralization front.
The amelogenin is used for the formation of calcium hydroxy apatite crystals. Voltage Gated Channels Voltage gated channels are opened by membrane depolarization Fig.
The channel is usually closed in the ground state. The membrane potential change voltage difference switches the ion channel to open, lasting less than 25 milliseconds. In voltage gated channels, the channels open or close in response to changes in membrane potential.
They pass from closed through open to inactivated state on depolarization. Once in the inactivated state, a channel cannot re-open until it has been reprimed by repolarization of the membrane.
Voltage gated sodium channels and voltage gated potassium channels are the common examples. These are seen in nerve cells and are involved in the conduction of nerve impulses.
Ion channels allow passage of molecules in accordance with the concentration gradient. Ion pumps can transport molecules against the gradient. The active transport is unidirectional. It requires specialized integral proteins called transporters. The transport system is saturated at higher concentrations of solutes. The transporters are susceptible to inhibition by specific organic or inorganic compounds.
General reaction is depicted in Figure 2. Sodium Pump It is the best example for active transport. Cell has low intracellular sodium; but concentration of potassium inside the cell is very high.
This is maintained by the sodiumpotassium activated ATPase, generally called as sodium pump. The ATPase is an integral protein of the membrane Fig. It has binding sites for ATP and sodium on the inner side and the potassium binding site is located outside the membrane. It is made up of two pairs of unequal subunits 2 2. Both subunits of the pump alpha and beta span the whole thickness of membrane.
Details are shown in Fig. Clinical applications of sodium pump are shown in Box 2. This would trigger muscle contraction. The function of calcium pump is to remove cytosolic calcium and maintain low. Ionophores They are membrane shuttles for specific ions. They transport antibiotics. Ionophores increase the permeability of membrane to ions by acting as channel formers. The two types of ionophores are; mobile ion carriers e.
Valinomycin and channel formers e. They are produced by certain microorganisms and are used as antibiotics. When cells of higher organisms are exposed to ionophores, the ion gradient is dissipated.
Valinomycin allows potassium to permeate mitochondria and so it dissipates the proton gradient; hence it acts as an uncoupler of electron transport chain Chapter Active Transport The salient features of active transport are: This form of transport requires energy.
Clinical Applications of Sodium Pump Cardiotonic drugs like digoxin and ouabain bind to the alpha-subunit and act as competitive inhibitor of potassium ion binding to the pump.
This would enhance the contractility of the cardiac muscle and so improve the function of the heart. Chapter 2; Subcellular Organelles and Cell Membranes 17 against a concentration gradient is coupled with movement of a second substance down the concentration gradient; the second molecule being already concentrated within the cell by an energy requiring process.
The co-transport system may either be a symport or an antiport. In symport , Fig. Phlorhizin, an inhibitor of sodium-dependent co-transport of glucose, especially in the proximal convoluted tubules of kidney, produces renal damage and results in renal glycosuria. Amino acid transport is another example for symport.
The antiport system Fig. Features of different types of transport modalities are summarized in Table 2. Clinical Applications In Hartnup's disease, transport mechanisms for amino acids are defective in intestine and renal tubules Chapter In cystinuria , renal reabsorption of cysteine is abnormal Chapter Renal reabsorption of phosphate is decreased in vitamin D resistant rickets Chapter Diseases due to abnormalities of transport systems include familial hypercholesterolemia, cystic fibrosis, congenital long QT syndrome, Wilson disease, I-cell disease, hereditary spherocytosis and paroxysmal nocturnal hemoglobinuria, etc.
Exocytosis cytosolic concentration, so that muscle can receive the next signal. Uniport, Symport and Antiport Transport systems are classified as uniport, symport and antiport systems Fig. Uniport system carries single solute across the membrane, e.
Calcium pump is another example. If the transfer of one molecule depends on simultaneous or sequential transfer of another molecule, it is called co-transport system.
The active transport may be coupled with energy indirectly. Here, movement of the substance. Different types of endocytosis. Left side, phagocytosis; middle, pinocytosis; right side, receptor mediated endocytosis.
Secretory Vesicles and Exocytosis Under appropriate stimuli, the secretory vesicles or vacuoles move towards and fuse with the plasma membrane. This movement is created by cytoplasmic contractile elements; the microtubule system.
The inner membrane of the vesicle fuses with outer plasma membrane, while cytoplasmic side of vesicle fuses with cytoplasmic side of plasma membrane. Thus the contents of vesicles are externalized.
This process is called exocytosis or reverse pinocytosis. Release of trypsinogen by pancreatic acinar cells; release of insulin by beta cells of Langerhans and release of acetyl choline by presynaptic cholinergic nerves are examples of exocytosis Fig. Often, hormones are the signal for exocytosis, which leads to calcium ion changes, triggerring the exocytosis. Endocytosis Endocytosis is the mechanism by which cells internalize extracellular macromolecules, to form an endocytic vesicle.
This requires energy in the form of ATP as well as calcium ions in the extracellular fluid. Cytoplasmic contractile elements take part in this movement. In general, plasma membrane is invaginated, enclosing the matter. This forms the endocytic vesicle.
The endocytosis may be pinocytosis or phagocytosis or receptor mediated endocytosis Fig. Pinocytosis Pinocytosis literally means drinking by the cell'. Cells take up fluid by this method Fig.
The fluid phase pinocytosis is a nonselective process. Receptor Mediated Endocytosis The selective or adsorptive pinocytosis is receptor mediated; also called as absorptive pinocytosis. The cytoplasmic side of these vesicles are coated with filaments; mainly composed of Clathrin. These are called Clathrin coated pits Fig. Absorption of cholesterol by clathrin coated pit is shown in Figure After the LDL-receptor complex is internalized, the receptor molecules are released back to cell surface; but the LDL is degraded by lysosomal enzymes.
Several hormones are also taken up by the cells by receptor-mediated mechanism. The protein, Dynamin which has GTPase activity, is necessary for the internalisation of clathrin coated pits. Many viruses get attached to their specific receptors on the cell membranes. They are taken up by caveolae mediated processes. Caveolae mediated endocytosis is also known as potocytosis.
Phagocytosis The term is derived from the Greek word "phagein" which means to eat. It is the engulfment of large particles such as bacteria by macrophages and granulocytes. They extend pseudopodia and surround the particles to form phagosomes Fig. Phagosomes later fuse with lysosomes to form phagolysosomes, inside which the particles are digested.
The biochemical events accompanying phagocytosis is described as respiratory burst Chapter Classification of amino acids based on structure 2. Based on side chain character 3. Based on metabolic fate 4. Based on nutritional requirements 5. Iso electric point 6.
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Reactions due to carboxyl group 7. Reactions due to amino group 8. Reactions of SH group 9. Peptide bond formation. Proteins are of paramount importance for biological systems. All the major structural and functional aspects of the body are carried out by protein molecules. All proteins are polymers of amino acids. Proteins are composed of a number of amino acids linked by peptide bonds. Although about amino acids occur in nature, only 20 of them are seen in human body.
Most of the amino acids except proline are alpha amino acids, which means that the amino group is attached to the same carbon atom to which the carboxyl group is attached Fig. Based on Structure 1-A. Aliphatic amino acids a. Mono amino mono carboxylic acids: Simple amino acids: Glycine, Alanine Fig. Valine, Leucine, Isoleucine Fig. Serine, Threonine Fig. Sulphur containing amino acids: Cysteine, Methionine Fig.
Asparagine, Glutamine Fig. Mono amino dicarboxylic acids: Aspartic acid, Glutamic acid Fig. Table 3. Di basic mono carboxylic acids: Lysine, Arginine Fig. Aromatic amino acids: Phenylalanine, Tyrosine Fig. Heterocyclic amino acids: Tryptophan Fig. Imino acid: Proline Fig. Derived amino acids: Derived amino acids found in proteins: After the synthesis of proteins, some of the amino acids are modified, e.
Gamma carboxylation of glutamic acid residues of proteins is important for clotting process Fig. In ribosomal proteins and in histones, amino acids are extensively methylated and acetylated. Derived amino acids not seen in proteins Non-protein amino acids: Some derived amino acids are seen free in cells, e. Ornithine Fig. These are produced during the metabolism of amino acids.
Thyroxine may be considered as derived from tyrosine. Non-alpha amino acids: Gamma amino butyric acid GABA is derived from glutamic acid. Beta alanine, where amino group is in beta position, is a constituent of pantothenic acid vitamin and co-enzyme A. Each amino acid will have three-letter and oneletter abbreviations which are shown in Table 3. Special Groups in Amino Acids In the figures, special groups are shaded.
Arginine contains guanidinium group; Phenyl alanine benzene ; Tyrosine phenol ; Tryptophan Indole ; Histidine imidazole ; and Proline pyrrolidine Table 3.
Proline has a secondary amino group, and hence it is an imino acid. Amino acids having nonpolar side chains: Chapter 3; Amino Acids: Structure and Properties 21 Box 3.
Arginine and Histidine are semi-essential amino acids; while others are essential 3. Purely Ketogenic Leucine is purely ketogenic because it is converted to ketone bodies Fig.
Histidine and proline These groups are hydrophobic water repellant and lipophilic. Therefore, the parts of proteins made up of these amino acids will be hydrophobic in nature.
Amino acids having uncharged or nonionic polar side chains: These amino acids are hydrophilic in nature. Tyrosine and Cysteine may show hydrophobic character when present in the interior of the protein. Amino acids having charged or ionic polar side chains hydrophilic: Acidic amino acids: They have a negative charge on the R group: Aspartic acid and Glutamic acid Tyrosine is mildly acidic.
Basic amino acids: They have a positive charge on the R group: Lysine, Arginine and Histidine. Ketogenic and Glucogenic Lysine, Isoleucine, Phenylalanine, Tyrosine and Tryptophan are partially ketogenic and partially glucogenic. How ever in humans lysine is predominantly ketogenic. During metabolism, part of the carbon skeleton of these amino acids will enter the ketogenic pathway and the other part to glucogenic pathway see Fig.
Purely Glucogenic All the remaining 14 amino acids are purely glucogenic as they enter only into the glucogenic pathway See Chapter Essential or Indispensable The amino acids may further be classified according to their essentiality for growth. Their carbon skeleton cannot be synthesized by human beings and so preformed amino acids are to be taken in food for normal growth. See memory aid in Box 3. Partially essential or Semi-essential Histidine and arginine are semi-indispensable amino acids.
Growing children require them in food. But they are not essential for the adult individual. Non-essential or Dispensable The remaining 10 amino acids are non-essential, because their carbon skeleton can be synthesized.
Selenocysteine as the 21st amino acid 21st century witnesses the addition of selenocysteine as the 21st amino acid present in human proteins. An amino acid is given the individual status, when it is incorporated as such into proteins during protein biosynthesis, and having a separate codon. Selenocysteine is present in some enzymes.
Instead of SH sulfhydryl group in cysteine, SeH selenium is present in selenocysteine. It is abbreviated as SeCys or SeC. Details are given in Chapter 15, under serine. Similarly pyrrolysine Pyl is known as the 22nd amino acid. Pyrrolysine is a lysine in an amide linkage to substituted-pyrrolinecarboxylate.
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It is present in methyl transferase enzymes of certain bacteria. Both SeC and Pyl are encoded by codons that normally function as stop signals. However, they are also required for normal protein synthesis. All body proteins do contain all the non-essential amino acids.
Naming Numbering of Carbon Atoms Carbon atoms in amino acids in sequence are named with letters of Greek alphabets, starting from the carbon atom to which carboxyl group is attached. As examples, naming of glutamic acid is shown in figure 3. Sodium glutamate is a flavoring agent. Aspartame, an artificial sweetener contains aspartic acid and phenyl alanine. All amino acids have high melting points more than C.
All amino acids are soluble in water and alcohol polar solvents ; but insoluble in nonpolar solvents benzene. Ampholyte and Iso-electric Point 1. The pH at which the molecule carries no net charge is known as iso-electric point or isoelectric pH pI. In acidic solution they are cationic in form and in alkaline solution they behave as anions Fig.
At iso-electric point the amino acid will carry no net charge; all the groups are ionized but the charges will cancel each other. Therefore at isoelectric point, there is no mobility in an electrical field.
Solubility and buffering capacity will be minimum at iso-electric pH. If more HCl is added, more molecules become cationic in nature and solubility increases. On the other hand, if we titrate the solution from iso-electric point with NaOH, molecules acquire the anionic form.
The iso-electric pH pI for mono amino mono carboxylic amino acids can be calculated:. L and D amino acids B. Optical Activity 1. Amino acids having an asymmetric carbon atom exhibit optical activity. Asymmetry arises when 4 different groups are attached to the same carbon atom Fig.
Glycine is the simplest amino acid and has no asymmetric carbon atom and therefore shows no optical activity. All others are optically active. The mirror image forms produced with reference to the alpha carbon atom, are called D and L isomers. The L-amino acids occur in nature and are therefore called natural amino acids. D-amino acids are seen in small amounts in microorganisms and as constituents of certain antibiotics such as Gramicidin-S, Polymyxin, Actinomycin-D and Valinomycin, as well as bacterial cell wall peptidoglycans.
Isoleucine and threonine have 2 optically active centers and therefore each has 4 diastereo isomers. Sorensen's Formal Titration Amino acids cannot be exactly titrated.
If, for example, 1 ml of 1N solution of glycine is titrated against 1N sodium hydroxide, the alkali requirement will be less than 1 ml. This is because hydrogen ions released by ionization of carboxyl group are partly taken up by the amino group. To circumvent this problem, excess formaldehyde is added to the solution, which converts amino group into neutral dimethylol derivative. Thereafter, titration can be completed to the end point. In the above example, after addition of formaldehyde, exactly 1 ml of 1N sodium hydroxide is utilized in the titration.
From the graph it is evident that the buffering action is maximum in and around pK1 or at pK2 and minimum at pI Fig. In the case of amino acids having more than two ionizable groups, correspondingly there will be more pK values, e.
Aspartic acid Fig. The pK values of amino acids are given in Table 3. From these values, it can be seen that at physiological pH of 7.
Thus to be very correct, zwitterion forms are to be shown as the structures of amino acids. The pK value of imidazolium group of histidine is 6.
The buffering capacity of plasma proteins and hemoglobin is mainly due to histidine residue. Due to Carboxyl Group 1. The amino acids will undergo alpha decarboxylation to form the corresponding amine Fig. Thus some important amines are produced from amino acids. For example,. Transamination reaction In the body, Glutamic acid is the most common amino acid to undergo oxidative deamination.
Formation of carbamino compound: Carbon dioxide adds to the alpha amino group of amino acids to form carbamino compounds. The reaction occurs at alkaline pH and serves as a mechanism for the transport of carbon dioxide from tissues to the lungs by hemoglobin Chapter Reactions Due to Side Chains 6. The methyl group of Methionine, after activation, may be transferred to an acceptor which becomes methylated Chapter Amide Formation: The -COOH group of dicarboxylic amino acids other than alpha carboxyl can combine with ammonia to form the corresponding amide.
These amides are also components of protein structure. The amide group of glutamine serves as the source of nitrogen for nucleic acid synthesis. Reactions Due to Amino Group 3. The alpha amino group of amino acid can be transferred to alpha keto acid to form the corresponding new amino acid and alpha keto acid Fig. This is an important reaction in the body for the inter-conversion of amino acids and for synthesis of non-essential amino acids.
Oxidative Deamination: The alpha amino group is removed from the amino acid to form the corresponding keto acid and ammonia Fig. Structure and Properties 25 Table 3.Clinical Applications of the Equation 1. It requires specialized integral proteins called transporters.
Caveolae contain the protein caveolin, along with other receptor proteins. When equilibrium is reached, the distributions of ions are shown in Figure 1. Water is a polar molecule. The word "doctor" is derived from the Latin root, "docere", which means "to teach". Salient Features of Ion Channels 1.
Secondly, rapid progress has been made in the area of molecular biology during past few years, and these advances are to be reflected in this book also.
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