Chúng tôi vui mừng giới thiệu ấn bản thứ ba của Giáo trình Hóa sinh cho Sinh viên Nha khoa. Nhiều trường đại học và cao đẳng y tế ở Ấn Độ đã chấp nhận ấn bản thứ nhất và thứ hai của cuốn sách này như một trong những sách giáo khoa tiêu chuẩn. Với sự khiêm tốn, chúng tôi có thể tuyên bố rằng cộng đồng y tế của Ấn Độ đã đón nhận nồng nhiệt các ấn bản trước của cuốn sách này. Nhìn lại, thật hài lòng khi lưu ý rằng cuốn sách này đã phục vụ sinh viên và giảng viên trong vài năm qua. Cuốn sách này được soạn thảo theo giáo trình (sửa đổi năm 2007) do Hội đồng Nha khoa Ấn Độ biên soạn. Chúng tôi cũng đã tham khảo giáo trình của các khóa học nha khoa của nhiều trường đại học khác nhau. Trong ấn bản thứ ba này, chúng tôi đã xóa một số chi tiết bổ sung được hiển thị trong ấn bản thứ hai. Đồng thời, chúng tôi đã bổ sung thêm một số nội dung ở các chương khác nhau, vì điều đó là cần thiết để bắt kịp tốc độ phát triển của khoa học. Nhiều số liệu và bảng đã được cải thiện. Trong lần xuất bản thứ ba này, các điểm quan trọng được viết thành các chữ cái in đậm, để học sinh có thể dễ dàng nắm bắt đề tài. Cuốn sách này hiện đưa ra những điểm “phải biết”. Những ai muốn biết thêm thông tin chi tiết có thể tham khảo Sách Giáo khoa Hóa sinh dành cho Sinh viên Y khoa của chúng tôi, hiện đã được tái bản lần thứ 8. Một ngân hàng câu hỏi, được đưa ra ở cuối sách, bao gồm các câu hỏi tiểu luận và câu hỏi ghi chú ngắn, được tổng hợp từ các đề thi 10 năm qua của các trường đại học khác nhau. Những câu hỏi này sẽ lý tưởng cho học sinh chuẩn bị cho kỳ thi vào phút cuối. Sự giúp đỡ và hỗ trợ của các sinh viên của chúng tôi trong việc chuẩn bị cuốn sách này là rất lớn. Hình ảnh trên web, không được bảo vệ bản quyền, đã được sử dụng trong một số số liệu. Thành công đáng kể của cuốn sách là nhờ sự hỗ trợ tích cực của các nhà xuất bản. Đây là sự đánh giá cao của chúng tôi đối với sự hợp tác của Shri Jitendar P Vij (Chủ tịch Tập đoàn), Ông Ankit Vij (Chủ tịch Tập đoàn) của M s Jaypee Brothers Medical Publishers (P) Ltd, New Delhi, Ấn Độ và các cộng sự của họ. Chúng tôi hy vọng rằng lần xuất bản thứ ba này sẽ thân thiện hơn với học sinh và hấp dẫn hơn đối với giáo viên. Bây giờ điều này nằm trong tay bạn để đánh giá.
More than 99% of the human body is composed of 6 elements,i.e.oxygen, carbon, hydrogen,nitrogen, calcium and phosphorus.Humanbodyiscomposedofabout60% water,15%proteins,15%lipids,2%carbohydrates and8% minerals.
Biomolecules in living organisms are organized into a hierarchy that reflects increasing molecular complexity These biomolecules are covalently bonded to create macromolecules essential for cellular function, such as the conversion of glucose into glycogen and amino acids into proteins The primary types of complex biomolecules include proteins, polysaccharides, lipids, and nucleic acids.
The macromolecules associate with each other to form
Table 1.1: Important milestones in the history of
Rouell 1773 Isolated urea from urine
Lavoisier 1785 Oxidation of food stuffs
Edward Buchner 1897 Extracted the enzymes
Fiske & Subbarao 1929 Isolated ATP from muscle
Hans Krebs 1937 Citric acid cycle
Avery & Macleod 1944 DNA is genetic material
Watson & Crick 1953 Structure of DNA
Nirenberg &Matthai 1961 Genetic code in mRNA
Holley 1963 Sequenced gene for tRNA
Paul Berg 1972 Recombinant DNA technology Kary Mullis 1985 Polymerase chain reaction
Table 1.2: Comparison between prokaryotic cells and eukaryotic cells
Size Small Large; 1000 to 10,000 times
Cell wall Rigid Membrane of lipid bilayer
Nucleus Not defined Well defined
Organelles including mitochondria and lysosomes
Nil Several supramolecular systems, e.g ribosomes, lipoproteins
Finally at the highest level of organization in the hierarchy of cell structure, various supramolecular comple xes are further assembled into cell organelle In prokaryotes
(bacteria; Greek word “pro” = before; karyon = nucleus), these macromolecules are seen in a homogeneous matrix; but in eukaryotic cells (higher organisms; Greek word
“eu” = true), the cytoplasm contains various subcellular organelles Comparison of prokaryotes and eukaryotes are shown in Table 1.2.
When the cell membrane is disrupted, the organized particles inside the cell are externalized These are called subcellular organelles They are described below
It is the most prominent organelle of the cell All cells in the body contain nucleus, except mature RBCs in circulation
In some cells, nucleus occupies most of the available space, e.g small lymphocytes and spermatozoa (Fig.1.1)
Nucleus is surrounded by two membranes: the inner one is called perinuclear membrane with numerous pores
The outer membrane of the nucleus is continuous with the endoplasmic reticulum, while the nucleus houses DNA, the genetic material that regulates cellular functions DNA is organized with proteins to form chromosomes, and within the nucleus, DNA replication and RNA synthesis, or transcription, occur A lighter shaded region within the nucleus, known as the nucleolus, is responsible for RNA processing and ribosome synthesis, and it is particularly prominent in cells that are actively engaged in protein synthesis.
The endoplasmic reticulum (ER) is a network of interconnected membranes that form channels or cisternae, extending from the perinuclear envelope to the outer plasma membrane Under an electron microscope, this structure exhibits a railway track appearance, particularly evident in cells that actively synthesize proteins, such as immunoglobulin-secreting plasma cells The ER is responsible for the synthesis of proteins, glycoproteins, and lipoproteins, while also containing the enzyme cytochrome P-450, which plays a crucial role in detoxifying various drugs.
The endoplasmic reticulum (ER) serves as a critical area where carbohydrate groups are progressively attached to newly formed proteins These glycoproteins subsequently travel to the Golgi apparatus, where additional carbohydrate chains are added before secretion The primary role of the Golgi apparatus is to sort, package, and secrete proteins effectively.
Solid waste in a township is typically decomposed in incinerators, similar to how cellular waste is processed in lysosomes, which are enzyme-filled organelles Lysosomes contain enzymes that break down polysaccharides, lipids, proteins, and nucleic acids When endocytic vesicles and phagosomes merge with primary lysosomes, they form secondary lysosomes or digestive vacuoles, where foreign particles are progressively digested.
Subcellular Organelles and Cell Membranes 3
They are spherical, oval or rod-like bodies, about 0.5–1 micrometers in diameter and up to 7 micrometers in length
(Fig.1.1) Erythrocytes do not contain mitochondria The tail of sper matozoa 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 (See Chapter 13)
Mitochondria feature two membranes, with the inner membrane intricately folded into structures known as cristae This membrane houses the enzymes essential for the electron transport chain, while the fluid matrix contains the enzymes necessary for the citric acid cycle Additionally, mitochondria possess specific components crucial for their function.
Mitochondrial DNA encodes essential information for the synthesis of specific mitochondrial proteins, playing a crucial role in the division of mitochondria While antibiotics that inhibit bacterial protein synthesis do not impact cellular processes, they do interfere with mitochondrial protein biosynthesis The functions of these organelles are significant for cellular health and energy production.
The plasma membrane acts as a barrier, distinguishing the cell from its external environment while also compartmentalizing various cellular components to facilitate organized activities Its selective permeability ensures that essential substances can enter and exit the cell efficiently.
Table 1.4: Comparison of Cell with a Factory
Plasma membrane Fence with gates; gates open when message is received
Endoplasmic reticulum Conveyer belt of production units Golgi apparatus Packing units
Vacuoles Lorries carrying finished products Mitochondria Power generating units
Table 1.3: Metabolic functions of subcellular organelles
Nucleus DNA replication, transcription Endoplasmic reticulum
Biosynthesis of proteins, glycoproteins, lipoproteins, drug metabolism Golgi body Maturation of synthesized proteins
Lysosome Degradation of proteins, carbohydrates, lipids and nucleotides
Mitochondria Electron transport chain, ATP generation, TCA cycle, beta oxidation of fatty acids, ketone body production
Cytosol Protein synthesis, glycolysis, glycogen metabolism, transaminations, fatty acid synthesis
Figure 1.1: A typical cell permeability properties so that the entry and exit of compounds are regulated The membrane is very active metabolically
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 contain cholesterol also
The Fluid Mosaic Model describes cell membranes as consisting of a lipid bilayer, where phospholipids are organized with polar head groups facing both the extracellular environment and the cytoplasm, creating a hydrophobic core in between.
(Fig 1.2) Each leaflet is 25 Å thick The total thickness is about 50 to 80 Å
The lipid bilayer shows free lateral movement of its components, hence the membrane is said to be fluid in nature
Membrane proteins are classified into two main types: peripheral proteins, which are located on the surfaces of the lipid bilayer and are connected through ionic and polar bonds to the lipid heads, and integral membrane proteins, which are embedded within the bilayer itself.
Some of the integral membrane proteins span the whole bilayer and they are called transmembrane proteins
They can serve as receptors (for hormones, growth factors, neurotransmitters), tissue specific antigens, ion channels, membrane based enzymes, etc
The permeability of substances across cell membranes is dependent on their solubility in lipids and not on their molecular size Water soluble compounds are generally
Figure 1.2: Fluid mosaic model of membrane impermeable and require carrier mediated transport Transport mechanisms are classified into:
Ion channels allow passage of molecules in accordance with the concentration gradient
Pumps can drive molecules against the gradient using energy.
Solutes and gases passively enter cells driven by the concentration gradient, with the entry rate depending on the solute's solubility in the membrane's hydrophobic core Simple diffusion occurs from areas of higher to lower concentration without the need for energy, although it is a relatively slow process.
Facilitated diffusion is a carrier-mediated transport process that allows structurally similar solutes to competitively inhibit each other's entry This mechanism operates without the need for energy, offering a transport rate that exceeds that of simple diffusion and is influenced by concentration gradients The regulation of carrier molecules is controlled by hormones, with glucose transporters serving as a key example of facilitated transport for glucose across the membrane.
Membranes contain specialized structures known as ion channels, which facilitate the rapid transport of essential electrolytes like calcium (Ca++), potassium (K+), sodium (Na+), and chloride (Cl ) These selective, ion-conductive pores are formed by specialized protein molecules that traverse the membrane, ensuring efficient ion movement.
Cation conductive channels typically remain closed but open in response to stimuli, allowing for a rapid influx of ions down their gradient, similar to a cinema gate opening for a crowd This mechanism is referred to as “gated” channels They are classified into two categories based on the stimuli that trigger their opening: “voltage-gated” channels, which respond to membrane depolarization, and “ligand-gated” channels, which open upon the binding of specific effectors.
It is a protein present in enamel of teeth has hydrophobic residues on the outside It acts as a calcium channel, which helps in mineralization (See Chapter 8).
Subcellular Organelles and Cell Membranes 5
The salient features of active transport are: (1) This form of transport requires energy About 40% of the total energy expenditure in a cell is used for the active transport system
(Fig 1.3) (2) It requires specialized integral proteins called transporters The transporters are susceptible to inhibition by specific organic or inorganic compounds.
Cells maintain a low concentration of sodium ions and a high concentration of potassium ions, primarily through the action of the sodium-potassium pump, also known as the sodium–potassium activated ATPase This pump utilizes the hydrolysis of one ATP molecule to expel three sodium ions (Na+) from the cell while bringing in two potassium ions (K+), ensuring the proper balance of these essential electrolytes.
The ion transport and ATP hydrolysis are tightly coupled
Clinical Applications: Cardiotonic drug digoxin inhibits the sodium–potassium pump This leads to an increase in Na + level inside the cell and extrusion of
Ca + from the myocardial cell This would enhance the contractility of the cardiac muscle and so improve the function of the heart.
2 Amino Acids and Proteins
Endocytosis is an energy-dependent process through which cells internalize extracellular macromolecules, resulting in the formation of an endocytic vesicle This mechanism requires ATP and calcium ions from the extracellular fluid, with cytoplasmic contractile elements facilitating the movement During endocytosis, the plasma membrane invaginates to enclose the material, creating the endocytic vesicle There are two main types of endocytosis: phagocytosis and receptor-mediated endocytosis.
Low-density lipoprotein (LDL) interacts with LDL receptors, leading to the internalization of the LDL-receptor complex This process involves vesicles coated with Clathrin filaments, known as Clathrin-coated pits Additionally, various hormones are absorbed by cells through receptor-mediated mechanisms, and several viruses, including influenza, hepatitis B, poliovirus, and HIV, attach to specific receptors on cell membranes.
The term "phagocytosis," originating from the Greek word "phagein," meaning "to eat," refers to the process by which macrophages and granulocytes engulf large particles like bacteria These immune cells extend pseudopodia to surround the particles, forming phagosomes that subsequently fuse with lysosomes to create phagolysosomes, where digestion occurs Remarkably, an active macrophage can ingest up to 25% of its volume every hour.
1 Marker enzymes are present only in particular organelle and used to identify these organelles during cell fractionation.
2 Nucleus is the storehouse of genetic information containing DNA organized into 23 pairs of chromosomes All cells in the body contain nucleus except mature erythrocytes.
3 Endoplasmic reticulum, a network of interconnecting membranes is the site of protein synthesis (Rough endoplasmic reticulum).
4 Smooth endoplasmic reticulum is the site for complex lipid and carbohydrate synthesis and detoxification of drugs.
Nascent proteins synthesized in the endoplasmic reticulum undergo modifications in the Golgi apparatus, where they are involved in glycosylation, protein sorting, packaging, and secretion before being exported to their specific destinations within the cell.
6 Lysosomes are bags of hydrolytic enzymes responsible for autophagy, postmortem autolysis and phagocytosis.
7 Mitochondria, the powerhouse of the cell has its own DNA encoding mitochondrial proteins and a role in triggering apoptosis.
8 Plasma membrane is mainly made up of phospholipid bilayers, interspersed with proteins and carbohydrate residues attached to proteins and lipids.
9 Cholesterol is also a component of animal cell membranes.
10 Phospholipid bilayers are oriented in such a way that there is a hydrophobic core with hydrophilic interior (cytoplasmic side) and outer layer (extracellular side).
11 Transmembrane proteins serve as receptors, tissue specific antigens, ion-channels, etc.
12 Membrane structure is described as the fluid mosaic model.
13 Short chain fatty acids and unsaturated fatty acids present in phospholipids will increase the fluidity of the membrane.
14 Cholesterol modulates the fluidity of membranes.
15 Lipophilic compounds can easily pass through the lipid membrane whereas hydrophilic molecules may require channels or pores.
16 Transport of molecules across the plasma membrane may be energy dependent (active) or energy independent (passive).
17 Active transport involves expenditure of energy and occurs against a concentration gradient.
18 Na + /K +– ATPase (Sodium pump) is an example of Active transport Cardiotonic drugs like Digoxin and Ouabain competitively inhibit
19 Ion channels that transport Na + , K + , Ca ++ and Cl – are transmembrane proteins They are highly selective They may be voltage gated or ligand gated.
20 Glucose transporters are examples of uniport transport by facilitated diffusion.
21 Sodium-dependent glucose transport in intestine and renal tubules are examples of symport systems.
22 Sodium-potassium-ATPase is an active transport system which causes efflux of sodium and influx of potassium with ATP hydrolysis.
Thereaderwill be able to answer questions on the followingtopics : 05
> Reactions due to carboxyl and amino groups
> Primary , secondary , tertiary and quaternary structure of proteins
The wordproteinisderivedfrom Greek word,"proteios” CLASSIFICATION OF AMINO ACIDS which means primary.Asthe name shows,the proteins are of paramount importance for biological systems 1 Based on Structure
Proteins constitute three-quarters of the total dry body weight and play a crucial role in body building They are essential for both the structural and functional aspects of the body Any abnormalities in protein structure can result in molecular diseases, significantly affecting metabolic functions.
Proteinscontaincarbon, hydrogen,oxygenandnitrogen asthemajorcomponentswhile sulfur and phosphorusare minor constituents.Nitrogen ischaracteristicofproteins.
On anaverage , the nitrogencontent of ordinaryproteins is
All proteins are polymers of amino acids Commonly occurring aminoacidsare 20 innumber.Mostoftheamino acids (exceptproline)arealphaaminoacids,which means that theaminogroupisattachedtothe samecarbonatomto which the carboxylgroupisattached(Fig.2.1).
Figure 2.5: Sulfur containing amino acids
Figure 2.6: Amino acids with amide groups
Mono amino dicarboxylic acids (Fig 2.7):
Name of amino acid Special group present 3-letter abbreviation 1-letter abbreviation
Aspartic acid Beta-carboxyl Asp D
Glutamic acid Gamma-carboxyl Glu E
Proline (imino acid) Pyrrolidine Pro P
Figure 2.10: Tryptophan (Trp) (W) with indole group
Figure 2.12: Some derived amino acids
Derived amino acids play a crucial role in protein structure and function Post-synthesis modifications of amino acids, such as hydroxyproline and hydroxylysine, are essential components of collagen, contributing to its stability Additionally, the gamma carboxylation of glutamic acid residues is vital for the clotting process Some derived amino acids, like ornithine, exist freely in cells and are classified as non-protein amino acids.
Citrulline, Homocysteine These are produced during the metabolism of amino acids
Each amino acid will have three-letter and one letter abbreviations which are shown in Figures 2.2 to 2.11, as well as in Table 2.1.
Special Groups in Amino Acids
Arginine features a guanidinium group, while phenylalanine is characterized by its benzene group Tyrosine contains a phenolic structure, and tryptophan is identified by its indole group Histidine has an imidazole ring, and proline is distinguished by its pyrrolidine structure, making it an imino acid due to its secondary amino group.
2 Classification Based on Side Chain
A Amino acids having nonpolar side chains: These include alanine, valine, leucine, isoleucine, me- thionine, proline, phenylalanine and tryptophan These groups are hydrophobic (water repellant) and lipophilic
B Amino acids having uncharged or non-ionic polar side chains:
Glycine, serine, threonine, cysteine, tyrosine, glutamine and asparagine belong to this group These amino acids are hydrophilic in nature
C Amino acids having charged or ionic polar side chains:
Hydrophilic amino acids play a crucial role in protein structure and function Acidic amino acids, such as aspartic acid and glutamic acid, carry a negative charge on their R group, while basic amino acids like lysine, arginine, and histidine possess a positive charge Additionally, tyrosine is considered mildly acidic Understanding these properties is essential for comprehending the behavior of proteins in biological systems.
3 Classification Based on Metabolic Fate
Leucine is purely ketogenic because it will enter into the metabolic pathway of ketogenesis
Lysine, isoleucine, phenylalanine, tyrosine, and tryptophan are amino acids that exhibit both ketogenic and glucogenic properties During their metabolism, portions of their carbon skeletons contribute to fatty acid synthesis, while the remaining parts are utilized in glucose production.
All the remaining 14 amino acids are purely glucogenic as they enter only into the glucogenic pathway
4 Classification Based on Nutritional Requirement
Amino acids are categorized based on their essentiality for growth, with isoleucine, leucine, threonine, lysine, methionine, phenylalanine, tryptophan, and valine identified as essential amino acids Since the human body cannot synthesize their carbon skeletons, it is crucial to obtain these preformed amino acids through diet for normal growth A helpful mnemonic to remember these essential amino acids is provided in Box 2.1.
B 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
The remaining 10 amino acids are classified as non-essential, yet they play a crucial role in normal protein synthesis While all body proteins include these non-essential amino acids, the body can synthesize their carbon skeletons through metabolic pathways Consequently, a lack of these amino acids in the diet does not negatively impact growth.
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 (Fig 2.7).
Amino acids can function as ampholytes or zwitterions depending on the solution's pH The isoelectric point (pI) is the specific pH at which an amino acid has no net charge, resulting in all ionizable groups being charged but canceling each other out In acidic conditions, amino acids exist as cations, while in alkaline conditions, they behave as anions At the isoelectric point, there is no mobility in an electrical field, and both solubility and buffering capacity are at their lowest.
In the context of monoamino monocarboxylic amino acids, the pH at which 50% of molecules exist as cations is referred to as pK1, relating to the carboxyl group (COOH) Conversely, the pH at which 50% of molecules exist as anions is known as pK2, associated with the amino group (NH2) The isoelectric point (pI) of these amino acids can be calculated using the formula: pI = pK1 + pK2.
The buffering capacity of histidine is highest near its pK values, specifically around pK1 and pK2, while it is lowest at the isoelectric point (pI) With a pK value of 6.1 for the imidazolium group of histidine, it serves as an effective buffer in biological systems.
BOX 2.1: Memory aid for essential amino acids
“Any Help In Learning These Little Molecules Proves Truly
Arginine, Histidine, Isoleucine, Leucine, Threonine, Lysine,
Methionine, Phenylalanine, Tryptophan and Valine in that order.
Arginine and histidine are semi-essential amino acids; while others are essential Figure 2.13: Ionic forms of amino acids
Amino Acids and Proteins 11 at the physiological pH of 7.4 The buffering capacity of plasma proteins and hemoglobin is mainly due to histidine residue.
Amino acids with an asymmetric carbon atom display optical activity due to the presence of four different groups attached to the same carbon Glycine, the simplest amino acid, lacks an asymmetric carbon and does not exhibit optical activity, while all other amino acids are optically active The mirror image forms related to the alpha carbon are referred to as D and L isomers.