Maintenance of Tissues/The Process of Tissue Renewal Flashcards
1
Q
Define muscle tissue
A
A soft tissue that composes muscles in animal bodies, and gives rise to muscles’ ability to contract. In mammals the three types are: skeletal or striated muscle; smooth or non-striated muscle; and cardiac muscle, which is sometimes known as semi-striated.
2
Q
Define Epithelium
A
The thin tissue forming the outer layer of a body’s surface and lining the alimentary canal and other hollow structures. the part of the epithelium derived from embryonic ectoderm and endoderm, as distinct from endothelium and mesothelium. composed with little or no intercellular substance cubical long processes(myepithelial cells) 1. epithelial membrane(internal protective kining, specialized to form function of secretion, excretion, transport etc., simple columnar, striatifies epithelium(multiple cells) and subdivided
3
Q
Define Simple Squamous Epithelium
A
This epithelial is membrane is formed of a single layer of flattened cells (thin walled tubules in the medula of the kidney, the endothelium-lining vessels and mesothilium-lining body cavities)
4
Q
Define Simple Cuboidal Epithelium
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It is formed of a single layer of hexagonal cells of moderate height(they form mainly a protective covering as of the ovary or protective lining, as in ducts but they assume a secretory function as in the thyroid Amniotic surface of placenta
5
Q
Define Simple Columnar Epithelium
A
This epithelial membrane is formed from a single layer of columnar cells( lining of the alimentary tract) Alveolus of prostate gland with a striated (brush) border . Small intestine. A single goblet cell is seen. The very dark nuclei belong to lymphocytes migrating through the epithelium.
6
Q
Define Pseudostratified Epithelium
A
All the cells are in contact with the basement membrane but all of them do not reach the luminal surface; the nuclei of the cells are arranged in 2 or more levels giving the appearance of multiple players(this type of epithelium lines the trachea and the ducts of the male reproductive systems). Vas deferens
7
Q
Define Striatified squamous epithelium
A
It has basal layer of columnar cells, few layers of polyhedral cells and a superficial layer of squamous cells( the stratified squamous epithelium present in a covering membrane(ex: the skin is exposed to the surface; keratization occurs in the cells of epithelium) Ceraminous gland of the external and meatus
8
Q
Define Striatified cuboidal or columnar epithelium
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It is observed in the cavernous urethra, conjuctional fornix and ducts of glands
9
Q
Define Transitional Epithelium
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In distention the epithelium resembles striatified squamous non-keratinized epithelium, when the epithelium is not stretched the superficial cells are rounded (urinary passages)
10
Q
Define Connective tissue
A
tissue that connects, supports, binds, or separates other tissues or organs, typically having relatively few cells embedded in an amorphous matrix, often with collagen or other fibres, and including cartilaginous, fatty, and elastic tissues. Delicate fibers: epimeysium endomysium periysium
11
Q
Atrial Natriurectic Factor
A
a peptide secreted by atrial cells regulating blood pressure and volume
12
Q
Bergmann’s cells
A
peculiar cells in the molecular layer of the cerebellar cortex having dendrites that extend outward through that layer
13
Q
Chondroblast
A
a cell that arises from the mesenchyma and forms cartilage
14
Q
Cochlear gangion
A
the sensory ganglion located within the spiral canal of the modiolus
15
Q
Endomysium
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the sheath of delicate reticular fibers which surrounds each muscle fiber
16
Q
Epimysium
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the fibrous sheath about the entire muscle
17
Q
Epineurism
A
the outermost layer of connective tissue of a peripheral nerve surrounding the entire nerve and containing its supplying blood vessels and its lymphatics
18
Q
Haversian Canal
A
nutrient canal of bone:one of the freely anastomosing channels of the haversian system if the compact bone which contains blood vessels, lymph vessels and nerves
19
Q
Mullers cells
A
elongated neurological cells traversing all the layers of the retina and forming its most important supporting element
20
Q
Neurilemma (Schwann’s membrane)
A
the thin membrane spirally ewrappingthe myelin layers of certain fibers especially of peripheral nerves or the axons of certain unmyelinated nerve fibers
21
Q
Neuroglia
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the supporting structure of nervous tissue
22
Q
Osteoblast
A
a cell which arises from a fibroblast and which as it matures is associated with the production of bone. reform bones bone forming cells
23
Q
Osteoclast
A
a large multi nuclear cell associated with the absorption and removal of the bone constantly break down the bone 18% of the bone is recycled bone absorbing cells; break
24
Q
Osteocyte
A
An oseoblast that has been embedded within the bone matrix occupying a flat oval cavity and sending through the canaliculi, slender cytoplasmic processes that make contact with the processes of other osteocytes Mature bone cells from osteoblasts maintain structure of bone
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Perichordium
the layer of dense fibrous connective tissue which invests all cartilage except the articular cartilage of synovial joints
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Perimysium
the connective tissue demarcating a fascicle of skeletal muscle fibres
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Perineurium
an intermediate layer of connective tissue in peripheral nerve surrounding each bundle of nerve fibers
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Pitiucyte
any of the dominant and distinctive fusiform cells of the neurohypophysis which are intermingled with nerve fibers and are regarded as specialized neurological cells
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Synapse
the site of the functional apposition between neurons at which an impulse is transmitted from one neuron to another
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Trigeminal nucleus
nucleus of the 5th cranial nerve
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Vestibular ganglion
the sensory ganglion located in the upper part of the lateral end of the internal acoustic meatus.
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Functions of the neurologia
1. The glial cells provide support to the neurons 2. They provide insulation for neurons and their processes limiting spread from the nerons 3. They maintain he metabolic and ionic environamnet of the nuerons 4. They remove neurotransmitters(released by presynaptic neuron) and metabolize them 5. They transport nutrients from the cappilaries to the neurons 6. they prevent growth of fibroblasts in the central nervous system 7. The microglial cells being the phagocytic macrophages particpate in processes of nerve regeneration; they remove they remove the necrotic tissue before proliferation of the microglial cells at the site of injury 8. Ependymal cells form a limiting epithelium lining the ventricles-central canal system; they upload and transport substances to the neurons and transport secretions of neurons to the cerebrospinal fluid
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Microglia
As the resident macrophage cells microglia actas the first and main form of actuve immune defense in the central nervous ysstem
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Macroglia
Astrocytes, oligodendrocytes, Mueller cells if the retinam Bargmann cells of the cerebellum
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Central nervous system neuroglia
Several fibrous astrocytes and many protoplasmic astrocytes can be made out
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Central nervous system, cerebellum
The cerebellum has grey matter(cortex) sperficially and white matter(medulla) deep to that. The surface is high folded
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Central nervous system, cerebellar cortex
The molecular layer Parkinje cell layer and granular layer can ber seen
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Central nervous system cerebellum and high power view of cerebellar cortex
Granular layer is separated from the molecular layer by the Parkinje cells and whose dendrites ramify i the molecular layer
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The peripheral nervous system ganglion of synapse
The plexus of Anerbach in the small intestine against a background of smooth muscle cut longitudinally
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Peripheral nervous system ganglionof synapse high power view.
Multipolar cells lying at random in a netwri of fine fibers the nuclei belong to satellite, Schwan and fibroblast cells
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Peripheral nervous system ganglionof synapse high power view.
Multipolar cells lying at random in a network of fine fibers the nuclei belong to satellite, Schwan and fibroblast cells
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Ganglion
a nerve cell cluster or a group of nerve cell bodies located in the peripheral nervous system
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Peripheral nervous system ganglion of synapse high power view.
Multipolar cells lying at random in a network of fine fibers the nuclei belong to satellite, Schwan and fibroblast cells
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Peripheral nervous system mixed peripheral nerve
The perineurium is at the top. The funicukus is composed of edullated and some medulalted fibers lyingin connective tissue(endoneurium)
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Peripheral nervous system LS mixed peripheral nerve
3 funicuki are sectioned and each is invested by concetric connective tissue cells(perineurium). The funiculi are seperated by loose connective tussue(epineurium).
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Peripheral nervous system mixed peripheral nerve perineurium
The funiculi are seperated by loose connective tissue(epineurium).
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Retinal bipolar cells
neurons of cochlear and vestibular ganglia
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Neural tissue
most of the central neurons. Neurona of the mesencephalic trigeminal nucleus and spinal ganglia
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Epineurium
the outermost layer if connective tissue of a peripheral nerve surrounding the entire nerve and containing in supplying blood vessels and lymphatics
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Endoneurium
loose connective tissue surrounding nerve fibers within a funiculus
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Osteoporosis
a disease where decreased bone strength increases the risk of broken bone and it may be due to lower than normal peak bone mass and greater than normal bone loss can occur because of alcoholism, anorexiam hyperthyroidism, surgical removing of the ovaries and kidney disease Bone loss increases after menopause due to lower levels of estrogen certain medications increase the rate of bone loss including chemotherapy, proton pomp inhibitors and steroids, not enough exercise and smoking are also risk factors
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Peak bone mass
maximum amount of bone a person has during life.
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Medications that increase rate of bone loss
chemotherapy, proton pomp inhibitors, selective serotonin re uptake inhibitors and steroids not enough exercise and smoking are also risk factors
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Bone remodelling
process of bone renewal
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Hematoma
blood clots in the space between broken bones in about 6-8 hours
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Fibrocartilaginous caiius
tissue repair begins, fibrocarilaginous callus fills space between ends of broken bones for about
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Bony callus
osteoblasts make thin plates of spongy bones and convert fibrocartilage callus to a bony callus and joins broken bones in about 3 to 4
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Remodelling
osteoblasts build new compact bone osteoblasts absorb spongy bone which created a new
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Osteoid
unmineralized organic portion of the bone matrix that forms prior to the maturation of bone tissue
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Formation of periosteum
the perichondrium becomes the periosteum, the periosteum contains a layer of the undifferentiatied cells(osteoprogenitor cells) which later become osteoblasts
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Formation of bone collar
the osteoblasts secrete osteoid against shaft of the cartilage model(appostional growth) this serves as support for the
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LS Skeletal muscle
The fibres are multinucleate. The cross-striations are not demonstrated well by used stain.
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TS smooth muscle
The fibers and their nuclei when sectioned are circular in outline
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Cardiac muscle
constitutes most of the heart but i is also located in the pulmonary veins and the superior vena cava
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Cardiac cycle
refers to a complete generation to the beginning and so including
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LS Cardiac muscle
The intercalated discs can be seen as dark bands running across the fibers. The cross striations are clearly visible. Cross striations can be seen clearly. Collagen is striated
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Pseudostratified (ciliated) columnar
Basement membrane(diagram)
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Ciliated columnar epithelium
Diagram
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Pseudostratified (ciliated) columnar
Basement membrane(diagram) Trachea Several rows of nuclei are present but every cell resets on the basement membrane
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Pseudostratified (ciliated) columnar
Basement membrane(diagram) Trachea Several rows of nuclei are present but every cell rests on the basement membrane
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Simple tubular glands
Simple tubular glands have cells arranged in test tube shaped secreting units. The secretion is pushed out through a single duct
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Simple tubular glands
Simple tubular glands have cells arranged in test tube shaped secreting units. The secretion is pushed out through a single duct simple test tube gland- body of uterus
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Simple alveolar gland
Sebaccous gland have their cells arranged in sac like structures that secrete through single ducts
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Compound tubular gland
Cervix of uterus a structure having branched ducts between the surface opening and the secreting portion
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Compound tubulo alveolar gland
Mammary gland Compound tubulo alveolar gland one of many multicellular glands with more than one secretory duct that contains both tube shaped and sac shaped portions
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Tubular secretory and alveolar structure
Diagram
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Functions of the general connective tissue 1.Sustenation
Sustenation: General connective tissue allows the diffusion f of oxygen and provides nurishment to the cells of the bod(except the central nervous system) and hence it is important in the sustenance of the life
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Functions of the general connective tissue 2. Diffusion of Metabolic Waste
Ground substance also allows for the diffusion of metabolic waste products from the cells of the various tissues into circulation
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Functions of the general connective tissue 3. Water and Electrolyte Balance
Molecules of the ground substance are importantin the maintenance of water and electrolyte balance owing to their affinity towards the electrolytes
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Functions of the general connective tissue 4. Storage
Approximately half the cirulating proteins are present in the connective tissue matrix. The proportion of albumin and globulin is different from the proportion found in plasma. Hence the ground substance may have a selective role in storage of the circulating proteins . At locations cells of the connective tissue are differentiated into adipocytes which store high energy-yielding fats
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Functions of the general connective tissue 5. Support
Loose connective tissue interconnecting different structures maintains their relationship . It provides the supporting blood vessels, nerves, tubular and all the delicate structures Dense connective tissue: in the mechanical role of support where the large tensile strength is required as in the ligaments. It forms a tough protective capsule and septa in the organs Elastic connective tissue: support where the suppleness is required as in the ligamentum flava Reticular tissue: provides support to the parenchyma and sinusoids by forming a delicate network in the glands The jelly like mucoid tissue provides support when rapid diffusion is required as in the embryo
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Functions of the general connective tissue 6. Locomotion
Dense connective tissue forms tendons and aponeurosis and translate muscle energy into movement and locomotion
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Functions of the general connective tissue 7. Distensibility
Elastic connective tissue imparts distensibility to hollow structures for periodic distention such as in the large arteries, trachea and bronchi
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Aponeuroses
layers of flat broad tendons. Their primary function is to join muscles and the body parts the muscles upon whether it be bone or muscle
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Loose connective tissue
hold in place and attaches epithelial tissue to other underlying tissues
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Dense connective tissue(dense regular, dense irregular)
has fibers that are not arranged in parallel bundles as in dense regular connective tissue. compromises a large portion of the dermis, Also in the protectvie kayer of the eyeball and in the deeper skin layers. It also makes up subaraucosa of the digestive tract, fibrous capsules and some types of fascia other examples include peritoseum and perichordhium and tunica albuginea fibres are the main matrix element provides connection between different tissues n the body tendons
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Elastic connective tissue
body tissue that contains a large amount of elastin one of the proteins that make up the connective tissue in general elastin is the protein that allows for tissue to regain its shape after being compressed or warped
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Adipose connective tissue
composed in large measure of fat cells whose fa globules has been dissolved during preparation and they appear in empty ghosts
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Areolar connective tissue
cell nuclei are brown the elastic fibers appear as fine brown lines and the collagen bundles as broad brown bands
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Tendon
a tough based of fibrous connective tissue that usually connects muscle to bone and is capable of withstanding tension. Tensons are similar to ligaments and fasciae, all 3 are made of colagen. Ligaments join 1 bone to another bone, fasciae connect muscles to other muscles bundles of dense collagen with star-shaped fibroblast nuclei are seen
91
Elastic fibers
present in relatively high concentration in several organs including the largest arteries in the body The labels indicate individual elsatic fibers(ef) in the aorta. The areas satined pink(between the elastic fibers) contain smooth muscle cells, reticular fibers and ground substance Black wavy lines are the elastic fibres, an organ containing these fibers are stretched. The fibers recoil and pull the organ back into
92
White fibrocartilage
insertion of supraspinatus tendon. The collagen bundles are seperated by rows of chondrocytes
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Chondrocytes
a mature cartilage cell embedded in a lacuna within the cartilage matrix
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Elastic cartilage
epiglottis. The branching elastic fibers are seen ramfying around the cartilage cells
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Elastic cartilage(epiglottis)
epiglottis. The branching elastic fibers are seen ramfying around the cartilage cells
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Elastic cartilage(external auditory meatus)
at the top is the perichondrium with fibroblasts below are flattened chondroblasts
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Elastic cartilage(external auditory meatus)
at the top is the perichondrium with fibroblasts below are flattened chondroblasts. The mature chondrocytes(bottom) are seperated by matrix which is of hyaline appearance
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Hyaline cartilage(costal cartilage)
The fibrous perichondrium is at the top below are flattened chondroblasts. The mature chondrocytes(bottom) lie in groups are seperated by hyaline matrix
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Mesenchyme
a loosely organized, mainly mesodermal embryonic tissue which develops into connective and skeletal tissues, including blood and lymph.
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Cancellous bone
high power view. The osteocytes are scattered in the homogenous bone matrix
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Cancellous bone
high power view. The osteocytes are scattered in the homogenous bone matrix. The spicules if bone are seperated by yellow marrow (adipose tissue)
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TS Compact bone
The cementing lines surrounding each haversian system are clearly delinerated
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2 processes resulting in formation of bone tissue
Intramembraneous ossification: is the direct laying down of bone into the primitive connective tissue(mesenchyme) ex: flat bones, bones of the skull Endochondral ossification: that involves cartilage as a precursor; ex: most bones of the human skeleton
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Intramembaneous ossification
Bones develop between sheets of fibrous tissue Cells from connective tissue cells become osteoblasts Osteoblasts secrete an organic The bones harden when the calcium salts are added to the organic Osteoblasts promote The first step in the process is the formation of bone spicules which eventually fuse with each other and become trabeculae. The periosteum is formed and bone growth continues at the surface of trabuculae. Much like spicules the increasing growth of trabuculae results in interconnection and this network is called woven bone
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Trabecula
a small often microscopic tissue element in the form of a small beam strut or rod generally having a mechanical function and usually composed of dense collagenous tissue
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Endochordal Ossification
The first site of ossification occurs in the primary center of ossification which is in the middle of diaphysis Formation of periosteum formation of bone collar Calcification of bone collar
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Formation of periosteum
The perichondrium becomes the periosteum the periosteum contains a layer of the undifferentiated cells(osteoprogenitor cells) which later become osteoblasts
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Formation of bone collar
The osteoblasts secrete osteoid against shaft of the cartilage model(apositional growth) the serves as support for the
109
Calcification of matrix
Chondrocytes in the primary center of ossification begin to growth they stop secreting collagen and proteoglycans and begin secreting alkaline phosphatase an enzyme essential for mineral deposition. Then calcification of the matrix occurs and osteoprogenitor cells that enetered the cavity via the periosteal bud, use the calcified matrix as a scalfold and begin secrete osteoid which forms the bone trbecula. Osetoclasts formed from macrophages break down spongy bone to form the medullary (bone marrow) cavity.
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Secondary ossification center
about the time of birth in mammals it appears in each end(epiphysis) of long bones. Periosteal buds carry mesenchyme and blood vessels in and the process is similar to that occuring in a primary ossification center. The cartilage between the primary and secondary ossification centers is called the epiphysical plate and it continues to form new cartilage which is replaced by the bone a process that results in an increase in length of the bone
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Muscle
specialized for contraction, composite tissues with elements of conductive tissues skeletal muscles have myoblasts which fuse together to form miotubes
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Sarcomere
z lines or z disks are dense protein disks that dont allow light i bands and a bands-h zone(m line connecting elements) actin and myosine pulled over to sacromere and they overlap, H zone is no longer visible
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Myofibrils
actine( thin) myosine(thick) and titin(spring that connects z line to m line) thick and thin elements sacromere muscles slide by contracting with myosine and actine
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cardiac muscle
cardiac(striated), smooth(most organs not well organized and are non striated) and skeletal muscle(movement) muscle fibers are separated by basement membrane cardiac muscle located in pulmonary veins and superior vena cava 1. striated cell centrally located single nucelus 2. 2/more branches 3. joined end to end intercelated disks ANF- atrial muscles streched contraction and relaxation of heart follows a certain cycle -cardica cycle SA node-AV node-AV bundle- intraventricular septum-divides to right and left-purkinje fibers large size and glycogen content
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Smooth muscle
without striation, force of contraction provided by smooth muscles, nucleus and non striated appearnace involuntary
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connective tissue
cells are dispersed(extracellular maters), loose and advanced, aponeuroses
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pigment cells
melanocytes and melanophores, which contain melanin; xanthophores, which contain carotenoids, flavins, and pterins; and iridocytes, or guanophores, which contain guanidine crystals.
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adipose tissue
fat cells, adiolar tissues, food reserve, mechanical buffers
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fibroblasts
cells producing collagen
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centroblasts
forms cartilage
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Neural tissue 2 systems
CNS(brain and spinal cord) PNS(Gaglia nerves and nerve endings) Peripheral-gagnlion, sensory/motor fibres epinerium, perineurium, endoneurium
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Neurons
golgi type 1(length of axon)golgi type 2 (shorter axon more branches cannot undergo mitosis 2 processes short(dandreids and long(axon)
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Exon
synapsises(connection) unipolar(dendtritic and axonial branches) bipolar(dentrites at one pole and axon at other multipolar(1 axon and several dentrites)
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Brain
grey matter(center surrounded by white in spinal cord and peripheral cortex) and white matter(axons and myelin which is why its white)
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Non axitable cells
neurologia and macro and microglia
126
Describe DNA replication
A self-correcting **DNA polymerase** catalyzes nucleotide polymerization in a **5'-to-3' direction**, copying a DNA template with remarkable fidelity. Since the two strands of a **DNA double helix are antiparallel**, this 5'-to-3' DNA synthesis can take place continuously on only one of the strands at a replication fork (**the leading strand**). On the **lagging strand** short DNA fragments are made by a "backstitching" process. Because the self-correcting DNA polymerase cannot start a new chain, these lagging-strand DNA fragments are primed by **short RNA primer molecules** that are subsequently erased and replaced with DNA.
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Proteins involves with DNA replication?
DNA replication requires the cooperation of many proteins, including **(1)** DNA polymerase and DNA primase to catalyze nucleoside triphosphate polymerization, **(2)** DNA helicases and singlestrand binding proteins to help open up the DNA helix so that it can be copied, **(3)** DNA ligase and an enzyme that degrades RNA primers to seal together the discontinuously synthesized lagging-strand DNA fragments, (**4)** DNA topoisomerases to help relieve helical winding and tangling problems, and **(5)** initiator proteins that bind to specific DNA sequences at a replication origin and catalyze the formation of a replication fork at that site.
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What happens at the **replication origin**?
At a replication origin a **specialized protein-DNA structure** is formed that subsequently **loads a DNA helicase** onto the DNA template; other proteins are then added to form the **multienzyme "replication machine"** that catalyzes DNA synthesis.
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Is this the correct image showing DNA replication?
Yes. The structure of a DNA replication fork. Because **both daughter DNA strands** (colored) are synthesized in the **5'-to-3' direction**, the DNA synthesized on the lagging strand must be made initially as a series of short DNA molecules, **called Okazaki fragments**
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Is this image of DNA replication correct?
An incorrect model for DNA replication. Although it might appear to be the simplest mechanism for DNA replication, **the mechanism illustrated here is not the one that cells use**. *Note that in this scheme both daughter DNA strands would grow continuously, using the energy of hydrolysis of the yellow phosphates to add the next nucleotide on each strand*. This would require chain growth in both the 5'- to-3' direction (bottom) and the 3'-to-5' direction (top). **No enzyme that catalyzes 3'-to-5' nucleotide polymerization** has ever been found.
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What process is happening here?
RNA primer synthesis. A schematic view of the reaction catalyzed by **DNA primase**, the enzyme that synthesizes the short RNA primers made on the lagging strand. Unlike DNA polymerase, this enzyme can **start a new polynucleotide chain** by joining two nucleoside triphosphates together. The **primase stops** after a short polynucleotide has been synthesized and makes the 3' end of this primer available for the DNA polymerase.
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Describe this image
Figure 6-44. The synthesis of one of the many DNA fragments on the lagging strand. In eucaryotes the RNA primers are made at intervals spaced by about 200 nucleotides on the lagging strand, and each RNA primer is 10 nucleotides long. This primer is erased by a special DNA repair enzyme that recognizes an RNA strand in an RNA/DNA helix and excises it; this leaves a gap that is filled in by DNA polymerase and DNA ligase, as we saw for the DNA repair process (see Figure 6-35).
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Pg 489
Figure 6-55. DNA topoisomerase II. An example of a DNA-helix-passing reaction catalyzed by a type II DNA topoisomerase. Unlike type I topoisomerases, these enzymes require ATP hydrolysis for their function, and some of the bacterial versions can introduce superhelical tension into DNA (see p. 438). Type II topoisomerases are largely confined to proliferating cells in eucaryotes; DNA Replication partly for that reason, they have been popular targets for anticancer drugs
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Pg 488- The reversible nicking reaction
Figure 6-54. The reversible nicking reaction catalyzed by a eucaryotic DNA topoisomerase I enzyme. As indicated, these enzymes form a transient covalent bond with DNA so as to allow free rotation about the covalent bonds linked to the blue phosphate
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Pg 487- The "winding problem" that arises during DNA replication
Figure 6-53. The "winding problem" that arises during DNA replication. For a bacterial replication fork moving at 500 nucleotides per second, the parental DNA helix ahead of the fork must rotate at 50 revolutions per second.
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Pg 486 The proteins that initiate DNA replication
Figure 6-52. The proteins that initiate DNA replication. The major types of proteins involved in the formation of replication forks at the E. coli and bacteriophage lambda replication origins are indicated. The mechanism shown was established by in vitro studies utilizing a mixture of highly purified proteins. Subsequent steps result in the initiation of three more DNA chains (see Figure 6- 51) by a pathway that is not yet clear. For E. coli DNA replication, the major initiator protein is the dnaA protein; for both lambda and E. coli, the primosome is composed of the dnaB (DNA helicase) and dnaG (DNA primase) proteins
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Pg 485 Replication fork initiation
Figure 6-51. Replication fork initiation. The figure outlines the processes involved in the initiation of replication forks at replication origins. (See also Figure 6-52.)
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Pg 484- A model for mismatch proofreading in eucaryotes.
Figure 6-50. A model for mismatch proofreading in eucaryotes. The two proteins shown are present in both bacteria and eucaryotic cells: MutS binds specifically to a mismatched base pair, while MutL scans the nearby DNA for a nick. Once a nick is found, MutL triggers the degradation of the nicked strand all the way back through the mismatch. Because nicks are largely confined to newly replicated strands in eucaryotes, replication errors are selectively removed. In bacteria the mechanism is the same except that an additional protein in the complex (MutH) nicks unmethylated (and therefore newly replicated) GATC sequences and thereby begins the process that is illustrated here. We know the mechanism because these reactions have been reconstituted in a cell-free system containing purified bacterial proteins and DNA.
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Pg 483- A replication fork in three dimensions
Figure 6-49. A replication fork in three dimensions. This diagram shows a current view of how the replication proteins are arranged at a replication fork when the fork is moving. The twodimensional structure of Figure 6-48 has been altered by folding the DNA on the lagging strand to bring the lagging-strand DNA polymerase molecule into a complex with the leading-strand DNA polymerase molecule. This folding process also brings the 3' end of each completed Okazaki fragment close to the start site for the next Okazaki fragment (compare with Figure 6-48). Because the lagging-strand DNA polymerase molecule is held to the rest of the replication proteins, it can be reused to synthesize successive Okazaki fragments; thus it is about to let go of its completed DNA fragment and move to the RNA primer that will be synthesized nearby, as required to start the next DNA fragment. Note that one daughter DNA helix extends toward the bottom right and the other toward the top left in this diagram.
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Pg 482 The proteins at a DNA replication fork.
Figure 6-48. The proteins at a DNA replication fork. The major types of proteins that act at a DNA replication fork are illustrated, showing their positions on the DNA
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Pg 482: The regulated sliding clamp that holds DNA polymerase on the DNA.
Figure 6-47. The regulated sliding clamp that holds DNA polymerase on the DNA. (A) The structure of the sliding clamp from E. coli, with a DNA helix added to indicate how the protein fits around DNA. A similar protein is present in eucaryotic cells. (B) Schematic illustration of how the clamp is thought to hold a moving DNA polymerase molecule on the DNA.
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Pg 480-The assay used to test for DNA helicase enzymes.
Figure 6-45. The assay used to test for DNA helicase enzymes. A short DNA fragment is annealed to a long DNA single strand to form a region of DNA double helix. The double helix is melted as the helicase runs along the DNA single strand, releasing the short DNA fragment in a reaction that requires the presence of both the helicase protein and ATP. The movement of the helicase is powered by its ATP hydrolysis
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Pg 481 - The effect of single-strand binding proteins on the structure of single-stranded DNA
The effect of single-strand binding proteins on the structure of single-stranded DNA. Because each protein molecule prefers to bind next to a previously bound molecule (cooperative binding) long rows of this protein will form on a DNA single strand. This cooperative binding straightens out the DNA template and facilitates the DNA polymerization process. The "hairpin helices" shown in the bare single-stranded DNA result from a chance matching of short regions of complementary nucleotide sequence; they are similar to the short helices that typically form in RNA molecules.
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Describe RNA and Protein synthesis
Before the synthesis of a protein, the corresponding mRNA molecule must be produced by DNA transcription. Then a small ribosomal subunit binds to the mRNA molecule at a start codon (AUG) that is recognized by a initiator tRNA molecule. A large ribosomal subunit binds to complete the ribosome and initiate the elongation phase of protein synthesis. During this phase aminoacyl tRNAs, each bearing a specific amino acid, sequentially bind to the appropriate codon in mRNA by forming complementary base pairs with the tRNA anticodon. Each amino acid is added to the carboxyl-terminal end of the growing polypeptide by means of a cycle of three sequential steps: aminoacyl-tRNA binding, followed by peptide bond formation, followed by ribosome translocation. The ribosome progresses from codon to codon in the 5'-to-3' direction along the mRNA molecule until one of three stop codons is reached. A release factor then binds to the stop codon, terminating translation and releasing the completed polypeptide from the ribosome. Eucaryotic and procaryotic ribosomes are highly homologous, despite substantial differences in the number and size of their rRNA and protein components. The predominant role of rRNA in ribosome structure and function is likely to reflect the ancient origin of protein synthesis, which is thought to have evolved in an environment dominated by RNA-mediated catalysis.
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What enzyme synthesizes RNA?
Pg 410 image
The synthesis of an RNA molecule by RNA polymerase. The enzyme binds to the promoter sequence on the DNA and begins its synthesis at a start site within the promoter. It completes its synthesis at a stop (termination) signal, whereupon both the polymerase and its completed RNA chain are released. During RNA chain elongation, polymerization rates average about 30 nucleotides per second at 37°C. Therefore, an RNA chain of 5000 nucleotides takes about 3 minutes to complete.
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Pg 411-The chain elongation reaction catalyzed by an RNA polymerase enzyme.
The chain elongation reaction catalyzed by an RNA polymerase enzyme. In each step an incoming ribonucleoside triphosphate is selected for its ability to base-pair with the exposed DNA template strand; a ribonucleoside monophosphate is then added to the growing, 3'-OH end of the RNA chain (red arrow), and pyrophosphate is released (red atoms). The new RNA chain therefore grows by one nucleotide at a time in the 5'-to-3' direction, and it is complementary in sequence to the DNA template strand. The reaction is driven both by the favorable free-energy change that accompanies the release of pyrophosphate and by the subsequent hydrolysis of the pyrophosphate to inorganic phosphate
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Start and Stop signal- Pg 412
Start and stop signals for RNA synthesis by a bacterial RNA polymerase. Here, the lower strand of DNA is the template strand, whereas the upper strand corresponds in sequence to the RNA that is made (note the substitution of U in RNA for T in DNA). (A) The polymerase begins transcribing at the start site. Two short sequences (shaded red), about -35 and -10 nucleotides from the start, determine where the polymerase binds; close relatives of these two hexanucleotide sequences, properly spaced from each other, specify the promoter for most E. coli genes. (B) A stop (termination) signal. The E. coliRNA polymerase stops when it synthesizes a run of U residues (shaded blue) from a complementary run of A residues on the template strand, provided that it has just synthesized a self-complementary RNA nucleotide sequence (shaded green), which rapidly forms a hairpin helix that is crucial for stopping transcription. The sequence of nucleotides in the self-complementary region can vary widely.
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Pg 413- DNA unwinding and rewinding by RNA polymerase
DNA unwinding and rewinding by RNA polymerase. A moving RNA polymerase molecule is continuously unwinding the DNA helix ahead of the polymerization site while rewinding the two DNA strands behind this site to displace the newly formed RNA chain. A short region of DNA/RNA helix is therefore formed only transiently, and the final RNA product is released as a single-stranded copy of one of the two DNA strands.
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Pg 414- RNA polymerase orientation determines which DNA strand serves as template.
RNA polymerase orientation determines which DNA strand serves as template. The DNA strand serving as template must be traversed from its 3' end to its 5' end, as illustrated in Figure 6-3. Thus the direction of RNA polymerase movement determines which of the two DNA strands will serve as a template for the synthesis of RNA, as shown here. Polymerase direction is, in turn, determined by the orientation of the promoter sequence, where the RNA polymerase initially binds. For the directions of transcription along a short portion of a bacterial chromosome, note that some genes are transcribed from one DNA strand, while others are transcribed from the other DNA strand.
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Pg 415 - The "cloverleaf" structure of tRNA.
The "cloverleaf" structure of tRNA. This is a view of the molecule shown in Figure 6-9 after it has been partially unfolded. There are many different tRNA molecules, including at least one for each kind of amino acid. Although they differ in nucleotide sequence, they all have the three stem loops shown plus an amino acid-accepting arm. The particular tRNA molecule shown binds phenylalanine and is therefore denoted tRNAPhe. In all tRNA molecules the amino acid is attached to the A residue of a CCA sequence at the 3' end of the molecule. Complementary basepairings are shown by red bars.
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Pg 416- The folded structure of a typical tRNA molecule
The folded structure of a typical tRNA molecule. Two views of the three-dimensional conformation determined by x-ray diffraction are shown. Note that the molecule is L-shaped; one end is designed to accept the amino acid, while the other end contains the three nucleotides of the anticodon. Each loop is colored to match
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Pg 416- A few of the unusual nucleotides found in tRNA molecules.
A few of the unusual nucleotides found in tRNA molecules. These nucleotides are produced by covalent modification of a normal nucleotide after it has been incorporated into an RNA chain. In most tRNA molecules about 10% of the nucleotides are modified
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Pg 418- Amino acid activation
Amino acid activation. The two-step process in which an amino acid (with its side chain denoted by R) is activated for protein synthesis by an aminoacyl-tRNA synthetase enzyme is shown. As indicated, the energy of ATP hydrolysis is used to attach each amino acid to its tRNA molecule in a high-energy linkage. The amino acid is first activated through the linkage of its carboxyl group directly to an AMP moiety, forming an adenylated amino acid;the linkage of the AMP, normally an unfavorable reaction, is driven by the hydrolysis of the ATP molecule that donates the AMP. Without leaving the synthetase enzyme, the AMP-linked carboxyl group on the amino acid is then transferred to a hydroxyl group on the sugar at the 3' end of the tRNA molecule. This transfer joins the amino acid by an activated ester linkage to the tRNA and forms the final aminoacyl-tRNA molecule. The synthetase enzyme is not shown in these diagrams.
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pg 418- The structure of the aminoacyl-tRNA linkage
The structure of the aminoacyl-tRNA linkage. The carboxyl end of the amino acid forms an ester bond to ribose. Because the hydrolysis of this ester bond is associated with a large favorable change in free energy, an amino acid held in this way is said to be activated. (A) Schematic drawing of the structure. (B) Actual structure corresponding to boxed region in (A). As in Figure 6-11, the "R-group" indicates the side chain of the amino acid
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Pg 418- Amino acid activation
Amino acid activation. The two-step process in which an amino acid (with its side chain denoted by R) is activated for protein synthesis by an aminoacyl-tRNA synthetase enzyme is shown. As indicated, the energy of ATP hydrolysis is used to attach each amino acid to its tRNA molecule in a high-energy linkage. The amino acid is first activated through the linkage of its carboxyl group directly to an AMP moiety, forming an adenylated amino acid;the linkage of the AMP, normally an unfavorable reaction, is driven by the hydrolysis of the ATP molecule that donates the AMP. Without leaving the synthetase enzyme, the AMP-linked carboxyl group on the amino acid is then transferred to a hydroxyl group on the sugar at the 3' end of the tRNA molecule. This transfer joins the amino acid by an activated ester linkage to the tRNA and forms the final aminoacyl-tRNA molecule. The synthetase enzyme is not shown in these diagrams
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Pg 240 - The recognition of a tRNA molecule
The recognition of a tRNA molecule by its aminoacyl-tRNA synthetase. For this tRNA (tRNAGln), specific nucleotides in both the anticodon (bottom) and the amino acid-accepting arm allow the correct tRNA to be recognized by the synthetase enzyme (blue)
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Pg 420 - The genetic code
The genetic code is translated by means of two sequential "adaptors". The first adaptor is the aminoacyl-tRNA synth-etase enzyme, which couples a par-ticular amino acid to its correspond-ing tRNA; the second adaptor is the tRNA molecule, whose anticodon forms base pairs with the appropriate nucleotide sequence (codon) on the mRNA. An error in either step will cause the wrong amino acid to be incorporated into a protein chain.
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Pg 421- The incorporation of an amino acid into a protein.
The incorporation of an amino acid into a protein.A poly-peptide chain grows by the stepwise addition of amino acids to its carboxyl-terminal end. The formation of each peptide bond is energetically favorable because the growing carboxyl terminus has been activated by the covalent attachment of a tRNA molecule. The peptidyl-tRNA linkage that activates the growing end is regenerated in each cycle. The amino acid side chains have been abbreviated as R1, R2, R3, and R4; as a reference point, all of the atoms in the second amino acid in the polypeptide chain are shaded gray
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Pg 422- Decoding an mRNA molecule
Decoding an mRNA molecule. Each amino acid added to the growing end of a file. RNA protein polypeptide chain is selected by complementary base-pairing between the anticodon on its attached tRNA molecule and the next codon on the mRNA chain Figure 6-17. The genetic code. The standard one-letter abbreviation for each amino acid
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Pg 423: The genetic code
The genetic code. The standard one-letter abbreviation for each amino acid is presented below its three-letter abbreviation. Codons are written with the 5'-terminal nucleotide on the left. Note that most amino acids are represented by more than one codon and that variation is common at the third nucleotide
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Pg 423: The ribosome
The ribosome. A three-dimensional model of the bacterial ribosome as viewed from two angles. The positions of many ribosomal proteins in this structure have been determined by using an electron microscope to visualize the positions where specific antibodies bind, as well as by measuring the neutron scattering from ribosomes containing one or more deuterated proteins.
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Pg 424: The structure of the rRNA in the small subunit.
The structure of the rRNA in the small subunit. This model of E. coli 16S rRNA is indicative of the complex folding that underlies the catalytic activities of the RNAs in the ribosome. The 16S rRNA molecule contains 1540 nucleotides, and it is folded into three domains: 5' (blue), central (red), and 3' (green)
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Pg 425: A comparison of the structures of procaryotic and eucaryotic ribosomes.
A comparison of the structures of procaryotic and eucaryotic ribosomes. Ribosomal components are commonly designated by their "S values," which indicate their rate of sedimentation in an ultracentrifuge. Despite the differences in the number and size of their rRNA and protein components, both types of ribosomes have nearly the same structure and they function in very similar ways. Although the 18S and 28S rRNAs of the eucaryotic ribosome contain many extra nucleotides not present in their bacterial counterparts, these nucleotides are present as multiple insertions that are thought to protrude as loops and leave the basic structure of each rRNA largely unchanged.
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Pg 426: The elongation phase of protein synthesis on a ribosome
The elongation phase of protein synthesis on a ribosome. The three-step cycle shown is repeated over and over during the synthesis of a protein chain. An aminoacyl-tRNA molecule binds to the A-site on the ribosome in step 1, a new peptide bond is formed in step 2, and the ribo-some moves a distance of three nucleotides along the mRNA chain in step 3, ejecting an old tRNA molecule and "resetting" the ribosome so that the next aminoacyl-tRNA molecule can bind. As indicated in Figure 6-21, the P-site is drawn on the left side of the file RNAyprotein ribosome, with the A-site on the right.
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Pg 427: Kinetic proofreading selects for the correct tRNA molecule on the ribosome.
Kinetic proofreading selects for the correct tRNA molecule on the ribosome. This more detailed view of step 1 of the elongation phase of protein synthesis shows how, in the initial binding event, an aminoacyl-tRNA molecule that is tightly bound to an elongation factor pairs transiently with the codon at the A-site. This pairing triggers GTP hydrolysis by the elongation factor, enabling the factor to dissociate from the aminoacyl-tRNA molecule, which can now participate in chain elongation (see Figure 6-22). A delay between aminoacyl tRNA binding and its availability for protein synthesis is thereby inserted into the protein synthesis mechanism. As a result, only those tRNAs with the correct anticodon are likely to remain paired to the mRNA long enough to be added to the growing polypeptide chain.The elongation factor, which is an abundant protein, is called EF-Tu in procaryotes and EF-1 in eucaryotes.
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Pg 428: The final phase of protein synthesis.
The final phase of protein synthesis. The binding of release factor to a stop codon terminates translation. The completed polypeptide is released, and the ribosome dissociates into its two separate subunits
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Pg 430: A three-dimensional model of a functioning bacterial ribosome
A three-dimensional model of a functioning bacterial ribosome. The small (dark green) subunit and the large (light green) subunit form a complex through which the messenger RNA is threaded. Although the exact paths of the mRNA and the nascent polypeptide chain are unknown, the addition of amino acids occurs in the general region shown, with the tRNAs held in the pocket formed between the large and small subunit
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Pg 431: The structure of the cap at the 5 ' end of eucaryotic mRNA molecules
The structure of the cap at the 5 ' end of eucaryotic mRNA molecules. Note the unusual 5'-to-5' linkage to the positively charged 7-methylguanosine and the methylation of the 2' hydroxyl group on the first ribose sugar in the RNA. (The second sugar may or may not be methylated.)
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Pg 432: A comparison of the structures of procaryotic and eucaryotic messenger RNA molecules
A comparison of the structures of procaryotic and eucaryotic messenger RNA molecules. Although both mRNAs are synthesized with a triphosphate group at the 5' end, the eucaryotic RNA molecule immediately acquires a 5' cap, which is part of the structure recognized by the small ribosomal subunit. Protein synthesis therefore begins at a start codon near the 5' end of the mRNA (see Figure 6-24). In procaryotes, by contrast, the 5' end has no special significance, and there can be multiple ribosome-binding sites (called Shine-Dalgarno sequences) in the interior of an mRNA chain, each resulting in the synthesis of a different protein
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Describe cells in mammals
Some cells in mammals - including nerve cells, heart muscle cells, sensory receptor cells for light and sound, and lens fibers - persist throughout life without dividing and without being replaced. In mature lens fibers the cell nuclei have degenerated and protein synthesis has stopped, so that the core of the adult lens consists of lens proteins laid down early in embryonic life. In most other permanent cells biosynthetic activity continues, and there is a steady turnover of cell components. In the rod cells of the retina, for example, new layers of photoreceptive membrane are synthesized close to the nucleus and are steadily displaced outward until they are eventually engulfed and digested by cells of the pigment epithelium
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Descrie the function of auditory cells
The auditory hair cells function as transducers, generating an electrical signal in response to sound vibrations that rock the organ of Corti and so cause the stereocilia to tilt. In mammals the auditory hair cells produced in the embryo have to last a lifetime: if they are destroyed by disease or by excessively loud noise, they are not regenerated and permanent deafness results
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When does Proliferation occur in the development of the lens of the human eye?
The development of the lens of a human eye. Proliferation occurs only in the anterior lens epi-thelial cells, which move posteriorly and differentiate into lens fibers.
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Explain the structure of the mature lens
The structure of the mature lens. (A) Light micrograph of part of the lens, showing the junction between the thin sheet of anterior lens epithelium that covers the front of the lens and the differentiated lens fibers to the rear. (B) Scanning electron micrograph of part of the lens. The lens fibers are closely stacked, like planks in a lumberyard. Each one is a single, lifeless, elongated cell that can be up to 12 mm long
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Pg 2131- Structure of the retina
The structure of the retina. The stimulation of the photoreceptors by light is relayed via the interneurons to the ganglion cells, which convey the signal to the brain. The spaces between neurons and between photoreceptors in the neural retina are occupied by a population of specialized supporting cells
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Explain the rod photoreceptor
A rod photoreceptor. (A) Schematic drawing. The actual number of photoreceptive discs in the outer segment is about 1000. (B) Electron micrograph of part of a rod photoreceptor, showing the base of the outer segment and the modified cilium that connects it to the inner segment.
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Explain the membrain protein in the rod cell
Pg 2132
Turnover of membrane protein in a rod cell. Following a pulse of 3 H-leucine, the passage of radiolabeled proteins through the cell is followed by autoradiography. Red dots indicate sites of radioactivity. The method reveals only the 3 H-leucine that has been incorporated into proteins; the rest is washed out during the preparation of the tissue. The incorporated leucine is first seen concentrated in the neighborhood of the Golgi apparatus (1). From there it passes to the base of the outer segment into a newly synthesized disc of photoreceptive membrane (2). New discs are formed at a rate of three or four per hour (in a mammal), displacing the older discs toward the pigment epithelium
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Describe differentiated cells
Most populations of differentiated cells in vertebrates are subject to turnover through cell death and cell division. In some cases, such as that of hepatocytes in the liver, the fully differentiated cells simply divide to produce daughter cells of the same type. Both the proliferation and the survival of hepatocytes are controlled to maintain appropriate total cell numbers. If a large part of the liver is destroyed, the remaining hepatocytes increase their division rate to restore the loss; and if hepatocyte proliferation is transiently increased by drug treatment, the increase in cell numbers is soon compensated for by an increase in cell death, returning cell numbers to normal. Such control mechanisms normally keep the numbers of cells of each type in a tissue in appropriate balance. In response to unusual damage, however, repair may be unbalanced, as when the fibroblasts in a repeatedly damaged liver grow too rapidly in relation to the hepatocytes and replace them with connective tissue
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Describe endothelial cells
Endothelial cells form a single cell layer that lines all blood vessels and regulates exchanges between the bloodstream and the surrounding tissues. New blood vessels develop from the walls of existing small vessels by the outgrowth of endothelial cells, which have the capacity to form hollow capillary tubes even when isolated in culture. In the living animal anoxic, damaged, or growing tissues stimulate angiogenesis by releasing angiogenic growth factors. These factors attract nearby endothelial cells and stimulate them to secrete proteases, to proliferate, and to form new capillaries.
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Describe structure if the liver
The structure of the liver. (A) Scanning electron micrograph of a portion of the liver, showing the irregular sheets of hepatocytes and the many small channels, or sinusoids, for the flow of blood. The larger channels are vessels that distribute and collect the blood that flows through the sinusoids. (B) The fine structure of the liver (highly schematized). The hepatocytes are separated from the bloodstream by a single thin sheet of endothelial cells with interspersed macrophagelike Kupffer cells. Small holes in the endothelial sheet allow exchange of molecules and small particles between the hepatocytes and the bloodstream while protecting the hepatocytes from buffeting by direct contact with the circulating blood cells. Besides exchanging materials with the blood, the hepatocytes form a system of minute bile canaliculi into which they secrete bile, which is ultimately discharged into the gut via bile ducts. The real structure is less regular than this diagram suggests. Some of the specialized cell types found in the epithelial lining of the gut. Neighboring positions in the epithelial sheet are often occupied by cells of dissimilar types
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What is gene expression?
the process by which information from a gene is used in the synthesis of a functional gene product
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Define regulation of gene expression
Refers to the control of the amount and timinf of appearance of the functional product of a gene.
Gives control over the structure and function and is the basis for cellular differentiation, morphogenesis and the versatality and adaptibility pf any organism
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Levels of gene regulation
Chromatin domains
Transcription
Post transcriptional modification
RNA transport
Translation
Post translation modification
mRNA degradation
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Chromatin domains and dna modifications in Eukaryotes
The accessbiliy of large regions of DNA depend on its chromatin structure which can be altered as a result of histone modifications directed by _DNA methylation, ncRNA, or DNA binding protein_
These modifications may up or down regulate the expression of a gene. Some of these modifications that regulate gene expression are inheritable and are referred to as **epigenetic regulation**.
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Describe transciption of a gene by RNA polymerase
can be regulated by several mechanisms. Regulation of transcription includes:
* Genetic(direct interaction of a control factor with the gene)
* Modulation interaction of a control factor with the transcription machinery
* Epigenetic(non sequence changes in DNA structure that influence transcription)
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Gene transcription factors
position RNA polymerase at the start of a protein coding sequence and then release the polymerase to transcribe the mRNA
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Activators
Enhance the interacction between RNA polymerase and a particular promoter, encouraging the experession of the gene. Activators fo this by increasing the atraction of RNA polymerase for the promoter thgough interactions with subunts of RNA polymerase or indirectly by changing the structure of the DNA
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Enhancers
sites on the DNA helix that are boud by activators in order to loop the DNA brinign a specific promoter to the initation complex
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Silencers
regions of DNA sequences that when bound by particular transcription factors can silence expression of the gene
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Post transcriptional modification
Exons and introns in the pre mRNA and the formation of mature mRNA by splicing the UTRs are noncoding parts of the exons at the ends of the mRNA
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Important modification of eukaryotic pre-mRNA
**RNA splicing**
The majority of eukaryotic pre-mRNAs consist of alternating segments called _exons and introns_. During splicing, an RNA protein catalytical complex(splicesome) catalyses two transesterification reactions which remove an intron and release it in form of lariat structure and then splice neighbouring exons together in certain cases, some introns or exons can be either removed or retained in mature mRNA. This so called **alternative splicing** creates series of different transcripts originating from a single gene. Because these transcripts are potenitially translated into different proteins, splicing extends the complexity of eukaryotic gene expression
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Describe the 3-UTRs (Three prime untranslated regions)
3-UTRs of mRNAs often contain regulatory sequences that post transcriptionally influence gene expression. Such 3-UTRs often contain both binding sites for micro-RNAs(miRNAs) as well as regulatory proteins. By binding to specific sites within the 3'UTR, miRNAs can decrease gene expression of various mRNAS by either inhibiting translation or by directly causing degradation of the transcript. The 3-UTRs also may have silencer regions that bind repressor proteins that inihibit the expressionof a mRNA.
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Translation of mRNA
Can be controlled mostly at the level of initiation. Recruitment of the small ribosomal subunit can be modulated by mRNA secondary structure, antisense RNA binding, or protein binding. In both prokaryotes and eukaryotes, a large number of RNA binding proteins exist, which often are directed to their target sequence by the secondary strcture of the transcript, which may cange depending on certain conditions, such as temperature or presence of a ligand(aptamer). Some transcripts act as ribosomes and self regulate their expression
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Antisense RNA(asRNA)
Single stranded RNA that is complemetary to a mRNA strand transcribed within a cell. Antisense RNA may inihibit translation of a complementary mRNA by base pairing to it and ohysically obstructing the translation machinery
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Post Translational modifications
Folding of Proteins
Each protein exists as an unfolded polypeptide or random coil when translated from a sequence of mRNA into a linear chain of amino acids; this polypeptide lacks any developed 3D structure. Amino acids interact with each other to poduce a well defined 3D structure, the folded protein known as the native state. The resulting 3D structure is detemined by the amino acid sequence.
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Why is the correct 3D structure essential when folding proteins?
It is essential for the protein to function although some parts of functional proteins may remain unfolded. Failure to fold into the intended shape usually produces inactive proteins with different properties including toxic prions. Several neurodegenerative and other diseases are believed to result from the accumulation of misfolded proteins.
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Which enzymes assist the newly formed proteinto fold into 3D structure if it needs to function?
Chaperones. RNA Chaperones help RNAs attain their functional shapes
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Describe Protein Degradation
Once protein sysnthesis is complete, the level of expression of that protein can be reduced by protein degradation. There are major protein degradation pathways of which the proteasome is a commmon component. A n unnneeded or damaged protein is often labeled for degradation by addition of **ubiquitin**
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mRNA Degradation
While transcription of prokaryotic protein coding genes creates mRNA that is ready for translation into protein, transcription of eukaryotic genes leaves a primary transcript of RNA(pre-RNA) which first has to undergo a series of modifications to become mature mRNA
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Describe the modifications that occur during RNA processing or mRNA degradation
**5' capping** which is a set of enzymatic reactions that add 7-methylguanosine(m7g) to the 5'end of pre-mRNA and thus protect the RNA fromdegradation by exonucleases. The m7G cap is then bound by **cap binding complex** hetodimer, which aids in mRNA export by cytoplasm and also protect the RNA from decapping
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What other modification happens after 5' capping modification?
**3' cleavage and polyadenylation**. They occur if polyadenylation signal sequence(5' AAUAA-3') is present in pre-mRNA which is usually between protein codding sequence and terminator. The pre-mRNA is first cleaved and then a series of - 200 adenines (A) are added to form poly(A) tail which protects the RNA from degradation. Poly(A) tail is bound by multiple **poly(A) binding proteins(FABP)** necessary for mRNA export and translatin re-initiation.
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Pemphigus
**Pemphigus vulgaris(PV)** and **pemphigus foliaceus (PF)** are autoimmune diseases of the skin which have as target antigens 2 different members of the desmoglein subfamily of the desmosomal cadherins, **demoglein-3** in the case of PV, and **desmoglein -1** in the case of PF
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What are desmogleins?
A family of cadherins consisting of protein s DSG1, DSG2, DSG3, DSG4, they play a role in the formation of desmosomes that join cells to one another
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What are desmosomes?
Are molecular complexes of cell adhesion proteins and linking proteins that attach the cell surface adhesion proteins to intracellular cytoskeletal filaments
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What are rhe cell adhesion proteins of the desmosome
Desmoglein and desmocolin are memebers of the cadherin family of cell adhesion molecules. They are transembrane proteins that bridge the space between adjacent epithelial cells by way of hemophilic binding of their extracellular domains to other desmosomal cadherins on the adjacent cell
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Describe the 2 dense structures of the cytoplasmic side of the plasma membrane
Center dense plaque (CDP) and inner dense plaque (IDP) these are spanned by the desmoplakin protein. The outer dense plaque is where the cytoplasmic domains of the cadherins attach to desmoplakin via plakoglobin and plakophilin; the inner dense plaque i where desmoplakin attaches to the intermediate filaments of the cytoskeleton
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mRNA degradation-Ekaryotic mRNA turnover
The polyA tail of mRNA is shortened by specialized exonucleases that are targeted to specific mRNAs. Poly(A) tail removal is thought to disrupt the circular structure of the message and destabilize the cap binding complex. The messaage is then subject to degradation by either the exosome complex or the decapping complex. In this way, translationally inactive messages can be destroyed quickly while active messenges ramain intact. The mechanism by which translation stops and the message is handed off to decay complexes is not understood in detail.
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AU- Rich element decay
The presence of AU-rich elements in mRNAs tends to destabilize those transcripts through the ction of cellular proteins that bind these sequences and stimulate polyA tail removal. Loss of poly A tail is thought to promote mRNA degradation by facilitating attack by both the exosome complex and the decapping complex.
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Small interfering RNA(siRNA)
Small interfering RNAs processed by the endoribonuclease **_Dicer_**are incorporated into a complex _RISC_ (RNA induced silencing complex).This complex contains an endonuclease that cleaves perfectly complementary messages to which the sRNA binds. The resulting mRNA fragements are then destroyed by exocucleases
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The exosome complex
is a multi protein intracellular complexcapable of degrading various types of RNA
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The mRNA decapping complex
A protein complex in eurkaryotic cells responsible for removal the 5'cap
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Small interfering RNA(Silencing RNA)
is a class of double stranded RNA molecules similar to miRNA and operated within the RNA interference pathway. It interferes with the expression of specific genes with complemetary nucleotide sequences by degrading mRNA after transcirtion, resulting in no translation.
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Micro-mRNAs(miRNAs)
Micro RNAs(mRNAs) are small RNAs that typically are partially complementary to sequences in mRNAs; binding of a miRNA to a message can repress translation of that message and accelerate poly A tail removal thereby hastening mRNA degradation
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Pemphigus: Signs and symptoms
Skin
Most patients with pemphigus vulgaris develop cutaneous lesions. The primary lesion of pemphigus vulgaris is a flaccid blister which usually arises on healthy appearing skin but may be found on erythematous skin. New blisters usually are flaccid or become flaccid quickly. Affected kin often is painful but rarely pruritic
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Pemphigus Signs and Symptoms
Muccous Membrane
Pemphigus vulgaris presents with oral lesions in 50-70% o patientsand almost al patients have mucosal lesions at sme pint in the course of their disease. Mucosal lesions may be the sole sign for an average of 5 months before skin lesions develop or tgey may be the sole manifestation of the disease.
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Pemphigus: Etiology
likely related to an underlying disruption in immune regulation. Most cases of PF and PV develop spontaneously. Rarely PV and PF may be associated with exposure to certain drugs. The geographic distribution of endemic PF parallels that of the black fly ehich is thought to be a possible vector involved in precipitating the disease but more recently other hematophagous insects such as the bedbugs and kissing bugs also have been suggested
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Is Pemphigus Vulgaris hereditary?
No, as it does not pass from generation to generation. Genetic factors are important but other factors are needed to trigger pemphigus vulgaris into activity
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Beta Catenin
principal interactions of structural proteins at cadherin-based adherens junction. Actin filaments are linked to a-actinin nd to membrane through vinculin. The head domain of vinculin associates to E - cadherin via catenins.
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Cadherins
transmembrane proteins forming adherens junctions to bind cells within tissues together
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Actin
is the monomeric subunit of 2 types of filaments in cells; microfilaments, one of the three major componenets of the cytoskeleton and thin filaments, part of the contractile apparatus in muscle cells
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Vinculin
A protein involved in the attachment of the actin-based microfilaments to the plasma membrane; alpha-catenins are evolutionary related to vinculin
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Primary mechanical role of Catenins
connecting cadherins to actin filaments specifically in adhesion junctions of the epithelial cells
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Alpha catenin can bind to?
B-catenin and can also bind actin. B-catenin binds cytoplasmic domain of some cadherins
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What is the dual role of beta catenin in the cell?
First of all, by binding to cadherin receptor, intracellular cytoplasmic tail domains, it can act as an integra compoent of a protein complex in adherens junctions that helps cells maintain epithelial layers. B-catenin acts by anchoring the actin cytoskeleton to the junctions, and may possibly aid in contact inhibition signaling within the cell- when an epithelial layer is complete and the adherens junctions indicate tha the cekk is surrounded. B=catenin may play a role in telling the cell to stop proliferating as there is no room for more cells in the area
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Define WNT(Int/Wingless)
A family of signaling glycoproteins, the name is combination(portmanteau) of Int and Wg for **Wingless-related integration site**
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Int 1
mouse protooncogen, desccribed in 1982 by Roel Nusse and Harold Varmus(first known member of the family)
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Wg
Gene/protein Wingless in drosophilia melanogaster , homologous to Int 1
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The canonical Wnt pathway (or Wnt/B-catenin pathway)
causes an accumulation B catenin in the cytoplasm and its eventual translocation into the nucleus to act as a transcriptional coactivator of transcription factors belongin to the TC/LEF family.
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Ubiquitin
is a small regulatory protein, its addtion to substrate proteins can signal for their degradation via the proteasome
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What happens when Wnt is not present
GSK-3B (Glycogen synthase kinase 3), a member of the pathway, is able to phosphorolate B-catenin as a result of a destruction complex formation that includes B-catenin, AXIN1, AXIN2, APC, protein phosphatase 2A, casein kinase 1a, and GSK3B. It degrades B-catenin by targeting it for ubiquination which subsequently send it to the proteasome to be digested. No translocation.
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What happens when Wnt is present?
GSK-3B is displaced from the complex causing B-catenin to not be phosphorylated and thus not ubiquinated. As a result, its levels in the cell are stabilized as it builds up in the cytoplasm. Eventually, some of this accumulated B-catenin will move into the nucleus, where B-catenin becomes a coactivator for transcription factors TCF and LEF to activate selected genes by displacing transcription repressors.
TCF=(T cell specific, HMG box) transcription factors
LEF=lymphoid enhancer-binding factor
TFs of the TCF/LEF family bind to DNA through a high mobility group division
Translocation
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Kallmann Syndrome
Congenital idiopathic hypogonadotropic hypogonadism is a disorder characterized by absent or incomplete sexual maturation by the age of 18 years in conjuction with low levels of circulating gonadotropins and testosterone and no other abonormalities of the hypothalamic-pituitary axis.
In the presence of anosmia, idiopathic hypogonadotrophic hypogonadism has been called Kallmann syndrome, whereas in the presence f a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism.
Kallmann syndrome can be inherited as an X -linked recessive trait, in which case there is a defect in the KAL1 gene(Xp22.3) encoding a neural cell adhesion molecule, anosmin-1. It is required to promote migration of GnRH neurons into the hypothalamus, it also allows migration of olfactory neurons from the olfactory bulbs to the hypothalamus
