73. Collagen – biosynthesis and degradation - Collagen is a group of naturally occurring proteins found, in nature, exclusively in animals, especially in the flesh and connective tissues of mammals.It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content. Collagen, in the form of elongated fibrils, is mostly found in fibrous tissues such as tendon, ligament and skin, and is also abundant in cornea, cartilage, bone, blood vessels, the gut, and intervertebral disc.

Collagen has an unusual amino acid composition and sequence:

• Glycine (Gly) is found at almost every third residue

• Proline (Pro) makes up about 17% of collagen

• Collagen contains two uncommon derivative amino acids not directly inserted during translation. These amino acids are found at specific locations relative to glycine and are modified post-translationally by different enzymes, both of which require vitamin C as a cofactor.

• Hydroxyproline (Hyp), derived from proline.

• Hydroxylysine (Hyl), derived from lysine (Lys). Depending on the type of collagen, varying numbers of hydroxylysines are glycosylated (mostly having disaccharides attached).

• Cortisol stimulates degradation of (skin) collagen into amino acids.

Synthesis

The synthesis of collagen occurs on the RER as individual preprocollagen chains (Fig. 4-7), which are α-chains possessing additional amino acid sequences, known as propeptides, at both the amino and carboxyl ends. As a preprocollagen molecule is being synthesized, it enters the cisterna of the RER, where it is modified. First, the signal sequence directing the molecule to the RER is removed; then some of the proline and lysine residues are hydroxylated (by the enzymes peptidyl proline hydroxylase and peptidyl lysine hydroxylase) in a process known as post-translational modification to form hydroxyproline and hydroxylysine, respectively. Subsequently, selected hydroxylysines are glycosylated by the addition of glucose and galactose.

Three preprocollagen molecules align with each other and assemble to form a tight helical configuration known as a procollagen molecule. It is believed that the precision of their alignment is accomplished by the propeptides. Because these propeptides do not wrap around each other, the procollagen molecule resembles a tightly wound rope with frayed ends. The propeptides apparently have the additional function of keeping the procollagen molecules soluble, thus preventing their spontaneous aggregation into collagen fibers within the cell.

The procollagen molecules leave the RER via transfer vesicles that transport them to the Golgi apparatus, where they are further modified by the addition of oligosaccharides. The modified procollagen molecules are packaged in the trans Golgi network and are immediately ferried out of the cell.

74. Non-colagen proteins Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form in a biologically functional way. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of adjacent amino acid residues. The sequence of amino acids in a protein is defined by the sequence of a gene, which is encoded in the genetic code. In general, the genetic code specifies 20 standard amino acids.

Most proteins consist of linear polymers built from series of up to 20 different L-α-amino acids. All proteinogenic amino acids possess common structural features, including an α-carbon to which an amino group, a carboxyl group, and a variable side chain are bonded. Only proline differs from this basic structure as it contains an unusual ring to the N-end amine group, which forces the CO–NH amide moiety into a fixed conformation. The side chains of the standard amino acids, detailed in the list of standard amino acids, have a great variety of chemical structures and properties; it is the combined effect of all of the amino acid side chains in a protein that ultimately determines its three-dimensional structure and its chemical reactivity.

The amino acids in a polypeptide chain are linked by peptide bonds. Once linked in the protein chain, an individual amino acid is called a residue, and the linked series of carbon, nitrogen, and oxygen atoms are known as the main chain or protein backbone. The peptide bond has two resonance forms that contribute some double-bond character and inhibit rotation around its axis, so that the alpha carbons are roughly coplanar. The other two dihedral angles in the peptide bond determine the local shape assumed by the protein backbone. The end of the protein with a free carboxyl group is known as the C-terminus or carboxy terminus, whereas the end with a free amino group is known as the N-terminus or amino terminus.

The words protein, polypeptide, and peptide are a little ambiguous and can overlap in meaning. Protein is generally used to refer to the complete biological molecule in a stable conformation, whereas peptide is generally reserved for a short amino acid oligomers often lacking a stable three-dimensional structure. However, the boundary between the two is not well defined and usually lies near 20–30 residues. Polypeptide can refer to any single linear chain of amino acids, usually regardless of length, but often implies an absence of a defined conformation.

75. hyaluronic acid  is an anionic, nonsulfated glycosaminoglycan. is a polysaccharide consisting of alternative residues of D-glucuronic acid and N-acetylglucosamine, and unlike other GAGs is not found as a proteoglycan. Hyaluronic acid in the extracellular space confers upon tissues the ability to resist compression by providing a counteracting turgor (swelling) force by absorbing significant amounts of water. Hyaluronic acid is thus found in abundance in the ECM of load-bearing joints. It is also a chief component of the interstitial gel. Hyaluronic acid is found on the inner surface of the cell membrane and is translocated out of the cell during biosynthesis.^[8]

Hyaluronic acid acts as an environmental cue that regulates cell behavior during embryonic development, healing processes, inflammation and tumor development. It interacts with a specific transmembrane receptor, CD44.

Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan (PG) in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins.^[5][6] It is in this form that HS binds to a variety of protein ligands and regulates a wide variety of biological activities, including developmental processes, angiogenesis, blood coagulation and tumour metastasis.

In the extracellular matrix, especially basement membranes, the multi-domain proteins perlecan, agrin and collagen XVIII are the main proteins to which heparan sulfate is attached.

Chondroitin sulfates contribute to the tensile strength of cartilage, tendons, ligaments and walls of the aorta. They have also been known to affect neuroplasticity.

Keratan sulfates have a variable sulfate content and unlike many other GAGs, do not contain uronic acid. They are present in the cornea, cartilage, bones and the horns of animals.

Glycoaminoglicans - This family of carbohydrates is essential or important for life.

GAGs form an important component of connective tissues. GAG chains may be covalently linked to a protein to form proteoglycans. Water sticks to GAGs; this is where the resistance to pressure comes from. The density of sugar molecules and the net negative charges attract cations, for example, Na+, which, after the sodium binds, attracts water molecules. Some examples of glycosaminoglycan uses in nature include heparin as an anticoagulant, hyaluronan as a component in the synovial fluid lubricant in body joints, and chondroitins, which can be found in connective tissues, cartilage, and tendons.

76. Chemical structure and organization of bone tissue: Osseous tissue, or bone tissue, is the major structural and supportive connective tissue of the body. Osseous tissue forms the rigid part of the bone organs that make up the skeletal system.

Formation: Bone tissue is a mineralized connective tissue. It is formed by cells, called osteoblasts, that deposit a matrix of Type-I collagen and also release calcium, magnesium, and phosphate ions that ultimately combine chemically within the collagenous matrix into a crystalline mineral, known as bone mineral, in the form of hydroxyapatite(Ca10(PO4)6(OH)2) . The combination of hard mineral and flexible collagen makes bone harder and stronger than cartilage without being brittle. Compact bone consists of a repeating structure called a Haversian system, or osteon, which is the primary anatomical and functional unit. Each osteon has concentric layers of mineralized matrix, called concentric lamellae, which are deposited around a central canal, also known as the Haversian canal, each containing a blood and nerve supply.

Types: There are two types of osseous tissue, compact and spongy. Compact bone forms the extremely hard exterior while spongy bone fills the hollow interior. The tissues are biologically identical; the difference is in how the microstructure is arranged.

Functions Osseous tissue performs numerous functions including: a) Directly: **Support for muscles, organs, and soft tissues. **Leverage and movement. **Protection of vital organs. e.g. the heart (Note: some vital organs may not be protected by bones. e.g. the intestines.), **Calcium phosphate storage. B) Indirectly: **Hemopoiesis - formation of blood cells (more correctly this is performed by the bone marrow interspersed within the spongy.

77. inorganic compound of enamel - Enamel Appetites: Apatite is a group of phosphate minerals, usually referring to hydroxyapatite,fluorapatite, chlorapatite and bromapatite, named for high concentrations of OH-, F-,Cl- or Br- ions, respectively, in the crystal. Fluorapatite (or fluoroapatite) is more resistant to acid attack than is hydroxyapatite. For this reason, toothpaste typically contains a source of fluoride anions. Enamel's primary mineral is hydroxylapatite, which is a crystalline calcium phosphate.[4] The large amount of minerals in enamel accounts not only for its strength but also for its brittleness. The hardest tiisue.

78. organic compounds of enamel:

Enamel is the hardest substance in the body. It is translucent, and its coloration is due to the color of the underlying dentin. Enamel consists of 96% calcium hydroxyapatite and 4% organic material and water. The calcified portion of enamel is composed of large crystals coated with a thin layer of organic matrix. The organic constituents of enamel are the keratin-like, high molecular weight glycoproteins, tyrosine-rich enamelins as well as a related protein, tuftleins.

Body_ID: P016015

Enamel is produced by cells known as ameloblasts, which elaborate enamel daily in 4- to 8-μm segments known as rod segments. Successive rod segments adhere to one another, forming keyhole-shaped enamel rods (prisms), which extend over the complete width of the enamel from the dentinoenamel junction to the enamel surface.

organic components:

Amelogenin is a protein found in developing tooth enamel, and it belongs to a family of extracellular matrix (ECM) proteins. Developing enamel contains about 30% protein, and 90% of this is amelogenins. Other significant proteins in enamel are ameloblastins,enamelins, and tuftelins.

Tuftelin is an acidic phosphorylated glycoprotein found in tooth enamel- it acts to start the mineralization process of enamel during tooth development.

Enamelin – soluble enamel protein,  modulator for mineral formation and crystal elongation in enamel.

79. Special features of dentin composition; its structure and functional organization.cementum.

DENTIN Its calcified tissue that is harder than bone because of its higher content of calcium salts. By weight it contains: *** 70% mineral hydroxyappetite (Ca10(PO4)6(OH)2 ) *** 20 % mineral materials : a) Glycosoaminoglycans, b) Phosphoproteins, c) Phospholipids *** 10% water. *** It consist of dental tubules, which radiate outward through the dentin from the pulp to the exterior cementum or enamel border.

Cementum is a specialized calcified substance covering the root of a tooth. Cementum is excreted by cells called cementoblasts within the root of the tooth and is thickest at the root apex.

Its composed of: * 65% inorganic material (hydroxyappetite), * 23% organic material (collagen , protein pollysacharides), * 12% water. Its main rol is to anchor the root by attaching it via periodontal ligament.

80. Pulp – The dental pulp is the part in the center of a tooth made up of living connective tissue and cells called odontoblasts.

Each person can have a total of up to 52 pulp organs, 32 in the permanent and 20 in the primary teeth. The total volumes of all the permanent teeth organs is 0.38cc and the mean volume of a single adult human pulp is 0.02cc.

The central region of the coronal and radicular pulp contains large nerve trunks and blood vessels.

This area is lined peripherally by a specialized odontogenic area which has three layers (from innermost to outermost)

1. Cell rich zone (of Rinaggio); innermost pulp layer which contains fibroblasts and undifferentiated mesenchymal cells.

2. Cell free zone (zone of Weil) which is rich in both capillaries and nerve networks. The nerve plexus of Raschkow is located in here

3. Odontoblastic layer; outermost layer which contains odontoblasts and lies next to the predentin and mature dentin

Cells found in the dental pulp include fibroblasts (the principal cell), odontoblasts, defence cells like histiocytes, macrophage, granulocytes, mast cells and plasma cells.

81. Amelogenesis  is the formation of enamel on teeth and occurs during the crown stage of tooth development after dentinogenesis, which is the formation of dentine. Although dentine must be present for enamel to be formed, it is also true that ameloblasts must be present in order for dentinogenesis to continue. A message is sent from the newly differentiated odontoblasts to the inner enamel epithelium (IEE), causing the epithelial cells to further differentiate into active secretory ameloblasts.

Inductive stage

Ameloblast differentiation is initiated by the presence of predentin. IDE cells elongate and become preameloblasts.

Initial Secretory stage

A shift in polarity occurs. Preameloblasts elongate and become postmitotic, polarized, secretory ameloblasts. No tomes' process yet. It is at this stage that a signal is sent from the newly differentiated ameloblasts back across the dental-enamel junction (DEJ) to stimulate dentinogenesis.

Secretory ameloblasts

Secretory stage ameloblasts are polarized, elongated cells with the cytoplasm full of organelles. Ameloblasts secrete organic matrix: enamel proteins and enzymes.

Secretory stage

In the secretory stage, ameloblasts are polarized columnar cells. In the rough endoplasmic reticulum of these cells, enamel proteins are released into the surrounding area and contribute to what is known as the enamel matrix, which is then partially mineralized by the enzyme alkaline phosphatase.

Maturation stage

In the maturation stage, the ameloblasts transport substances used in the formation of enamel.

 Proteins used for the final mineralization process compose most of the transported material. The noteworthy proteins involved are amelogenins, ameloblastins, enamelins, and tuftelins. During this process, amelogenins and ameloblastins are removed after use, leaving enamelins and tuftelin in the enamel. By the end of this stage, the enamel has completed its mineralization.

82. Actin - One of two proteins responsible for contraction of muscle cells and the motility of other cells. It occurs as a monomer, G-actin, a globular protein, and in living cells as a polymer, F-actin, which resembles two strings of beads twisted around each other into thin filaments. The filaments occur in regular structures, alternated and interwoven with thick filaments that contain myosin, the other major muscle protein. The thick and thin filaments slide past each other, under the control of calcium ions, resulting in contraction (shortening) and relaxation (lengthening) of the muscle cells

.Myosine - A contractile protein that forms the thicker of the two types of filaments in muscle fibres. Each myosin molecule is composed of two polypeptide chains twisted together. One end of each is folded into a globular head called the myosin head or myosin cross-bridge. In the presence of calcium ions, the heads with specific sites on the thinner actin filaments interact. The cross-bridges contain ATPase and generate the tension developed by a muscle fibre when it contracts

tropomyosin - A tube-shaped protein found in thin actin filaments of muscle fibres. Tropomyosin has a control function; when calcium ion concentration is low within a muscle fibre, the tropomyosin inhibits muscle contraction by blocking the binding site on actin, thereby preventing myosin cross-bridges from attaching

Troponin complex - is a heteromeric protein playing an important role in the regulation of skeletal and cardiac muscle contraction. Troponin complex consists of three different subunits – troponin T (TnT), troponin I (TnI) and troponin C (TnC). Each subunit is responsible for a part of troponin complex function. TnT is a tropomyosin-binding subunit which regulates the interaction of troponin complex with thin filaments; TnI inhibits ATP-ase activity of acto-myosin; TnC is a Ca2+ - binding subunit, playing the main role in Ca2+ dependent regulation of muscle contraction.

83. .Muscle contraction - The electrochemical process of generating tension within a muscle. You would be forgiven for thinking that when a muscle contracts it shortens. This does happen in some types of contraction (concentric contractions), but muscles can also lengthen during a contraction (eccentric contractions), or stay the same length (isometric contractions). Consequently, many exercise physiologists prefer to use the phrase ‘muscle action’, because this does not imply a change in muscle length.The main feature of muscle contraction is the interaction of actin, myosin and ATP. This fundamental process of contraction is regulated by the tropomyosin-troponin-Ca2+ system. It is accepted, that in the resting muscle tropomyosin (TM) is positioned in the groove of the actin double helix in a way that it sterically blocks the combination of myosin with actin. This is illustrated in Fig. RE1a, which shows a thin filament composed of actin, tropomyosin, and the components of troponin (TN-C, TN-I, TN-T). In the absence of Ca2+ (Relaxed state), TM blocks the crossbridge binding sites on actin. Binding of Ca2+ to TN-C (Activated state) initiates the TM movement, through TN-T, from the center of the actin strand to its side, thereby releasing the steric blocking. In addition, the TN-C-Ca2+ complex removes TN-I from its inhibitory position on actin; thus the combination of the myosin head with actin can take place. Since in the thin filament there is only one TN and one TM molecule per seven G-actin molecules, one has to assume that cooperative interactions play a major role in the regulation of contraction.

84. ATP is resynthesized in muscle by 4 ways: glycolysis, oxidative phosphorylation, creatinine kinase and adenylate kinase. First two are fundament for all tissues. During glycolysis, ATP is formed in two reactions at substrate level: phosphoglycerate kinase reaction and pyruvate kinase reaction. This reactions are anaerobic and that's why muscle can contract for some time in anaerobic condition. Energy of this process forms only 6-7% of total energy of carbohydrates. Positive side of muscle work: high energy efficacy, H2O and CO2 as final products, reserve of power material for this practicaly inexhaustible. During Creatnine Kinasa reaction, creatinine phosphate interacts with ADP forming ATP and creatine: creatine phosphate+ADP<=>Creatine+ATP Adenylate kinase 2ADP-->ATP+AMP

Work of muscle: Myofibril are serounded by sarcoplasmic reticulum( with T-tubules) Action of muscle is generatet by nerv impuls from brain whiche goes to membrane of muscle fibern and T-tubeles than it's spread on all muscle. In sacroplasmic reticulum when impuls arrive the Ca goes to myofibrils (myosin, actine)which causes disclosure of actin and the myosin head is atached this proces called CROSS-BRIDGE

Phosphocreatine can anaerobically donate a phosphate group to ADP to form ATP during the first 2 to 7 seconds following an intense muscular or neuronal effort. On the converse, excess ATP can be used during a period of low effort to convert creatine to phosphocreatine. The reversible phosphorylation of creatine (i.e., both the forward and backward reaction) is catalyzed by several creatine kinases. The presence of creatine kinase (CK-MB, MB for muscle/brain) in plasma is indicative of tissue damage and is used in the diagnosis of myocardial infarction.^[1] The cell's ability to generate phosphocreatine from excess ATP during rest, as well as its use of phosphocreatine for quick regeneration of ATP during - in this case, ATP. Phosphocreatine plays a particularly important role in tissues that have high, fluctuating energy demands such as muscle and brain.

85. Gangliosides is a molecule composed of a glycosphingolipid with one or more sialic acids linked on the sugar chain. Can amount to 6% of the weight of lipids from brain, where they constitute 10 to 12% of the total lipid content (20-25% of the outer layer) of neuronal membranes, for example. Cerebrosides Any one of a class of glycolipids in which a single sugar unit is bound to a sphingolipid. The most common cerebrosides are galactocerebrosides, containing the sugar group galactose; they are found in the plasma membranes of neural tissue and are abundant in the myelin sheaths of neuron. Amino acid neurotransmitters GABA, glutamate, aspirate and taurine were measured in 7 cerebral cortical regions from a group of both Parkinson’s disease and Alzheimer’s disease and from neurologically normal controls. Glutamic acid is accepted as the major excitatory neurotransmitter in the nervous system. It plays a major role in brain development, affecting neuronal migration, neuronal differentiation, axon genesis and neuronal surviva.

86. Acetylcholine Acetylcholine is an ester of acetic acid and choline with chemical formula CH₃COOCH₂CH₂N⁺(CH₃)₃. This structure is reflected in the systematic name, 2-acetoxy-N,N,N-trimethylethanaminium. Its receptors have very high binding constants.The chemical compound acetylcholine (often abbreviated ACh) is a neurotransmitter in both the peripheral nervous system (PNS) and central nervous system (CNS) in many organisms including humans. Acetylcholine is one of many neurotransmitters in the autonomic nervous system (ANS) and the only neurotransmitter used in the motor division of the somatic nervous system. (Sensory neurons use glutamate and various peptides at their synapses.) Acetylcholine is also the principal neurotransmitter in all autonomic ganglia.

Acetylcholine slows the heart rate when functioning as an inhibitory neurotransmitter. However, acetylcholine also behaves as an excitatory neurotransmitter at neuromuscular junctions.

Norepinephrine is a catecholamine and a phenethylamine. The natural stereoisomer is L-(−)-(R)-norepinephrine. The term "norepinephrine" is derived from the chemical prefix nor-, which indicates that norepinephrine is the next lower homolog of epinephrine. The two structures differ only in that epinephrine has a methyl group attached to its nitrogen, while the methyl group is replaced by a hydrogen atom in norepinephrine. The prefix nor- is likely derived as an abbreviation of the word "normal", used to indicate a demethylated compound

. Norepinephrine is synthesized from dopamine by dopamine β-hydroxylase.^[6] It is released from the adrenal medulla into the blood as a hormone, and is also a neurotransmitter in the central nervous system and sympathetic nervous system where it is released from noradrenergic neurons. The actions of norepinephrine are carried out via the binding to adrenergic receptors.

Dopamine has the chemical formula C₆H₃(OH)₂-CH₂-CH₂-NH₂. Its chemical name is "4-(2-aminoethyl)benzene-1,2-diol”. As a medicinal agent, dopamine is synthesized by demethylation of 2-(3,4-dimethoxyphenyl)ethylamine using hydrogen bromide. Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, thissubstituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D₁, D₂, D₃, D₄, and D₅—and their variants. Dopamine is produced in several areas of the brain, including the substantia nigra and the ventral tegmental area.

Serotonin (5-hydroxytryptamine) is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal (GI) tract, platelets, and in the central nervous system (CNS) of animals including humans.

87. A neurotransmitter receptor is a membrane receptor protein. A membrane protein interacts with the lipid bilayer that encloses the cell and a membrane receptor protein interacts with a chemical in the cells external environment, which binds to the cell. Membrane receptor proteins are particularly important in neuronal and glial cells (involved in neuronal transmission, but not technically neurons), because they allow cells to communicate with one another through chemical signals. Neurotransmitter receptors send and receive signals that trigger an electrical signal that runs along the neuron and can be passed along a neural network, by regulating the activity of ion channels ^[1] A neurotransmitter receptor can be paired directly with an ion channel, but most send signals indirectly through guanyl nucleotide-binding proteins or G proteins ^[2]Interactions between neurotransmitters and neurotransmitter receptors are involved in a wide range of differing reactions from the cell receiving the signal, triggering anything from activation to inhibition.