Patho Quiz 1 - Organelles/Cell Bio

What are the major steps that occur within the Golgi complex?

1) Instructions for making a protein are transcribed from DNA by RNA in the NUCLEUS 2) The RNA leaves the nucleus through a NUCLEAR PORE and proceeds to a RIBOSOME located on the rER 3) Instructions are provided for the correct amino acid sequence to produce the correct enzyme 4) When the enzyme is made, it travels through the ER and is then encapsulated into a TRANSPORT VESICLE 5) The transport vesicle FUSES with a GOLGI BODY, releasing the enzyme into the GOLGI COMPLEX 6) The enzyme is further modified, then shunted to the cisternae. The enzyme waits here for a SECRETORY VESICLE 7) The sec. ves. carries the enzyme to the PM, fuses it, and the enzyme is released outside of the cell

What are the 8 chief cellular functions?

1) MOVEMENT -Muscle cells generate forces that produce motion 2) CONDUCTIVITY -Electrical potential that passes along the cell surface 3) METABOLIC ABSORPTION -Use of nutrients (kidneys, intestines, etc.) 4) SECRETION -Synthesis of substances to secrete (mucous glands, adrenal, etc.) 5) EXCRETION -Ridding waste products from metabolism 6) RESPIRTATION -Absorbing O2 which converts nutrients to energy 7) REPRODUCTION -Tissue growth and maintenance 8) COMMUNICATION -Allows maintenance of a dynamic/steady state

What are the 3 main components of a typical euk. cell?

1) PLASMA MEMBRANE/plasmalemma . 2) CYTOPLASM . 3) INTRACELLULAR ORGANELLES -membrane-bound -includes the nucleus

Eukaryotic: Describe the main components of the PLASMA MEMBRANE (PM)

-Crucial to normal physiologic function bc they control the composition of the entity they enclose -Due to selective transport systems (semi-permeable/highly selective), they exert a powerful influence on metabolic pathways -CELL POLARITY - controls the direction of cells (distinct apical and basolateral domains) which maintains the normal cell and tissue structure for various functions -CELL TO CELL RECOGNITION (markers) -Assists with cellular mobility and maintenance of cell shape *See Table 1.1 in text book for Plasma Membrane Functions

Eukaryotic: Describe the main components of the CYTOSOL/CYTOPLASM

-Cytosol = Aqueous solution -Fills cytoplasmic matrix (space bt nuclear envelope & plasma membrane) -Represents ~1/2 the volume of a euk cell -Has 1000's of enzymes involved in intermediate metabolism -Crowded with ribosomes

Eukaryotic: Describe the main components of the PROTEASOMES

-Degrades unwanted/damaged proteins that are in the cytosol -Proteotoxic Stress: elevated temps increase heat-shock proteins (HSPs) due to more misfolded proteins --> help proteins to refold properly -UBIQUITIN: Signals the protein to the proteasome for degradation -Important for cell function and metabolic control

Primary vs. Secondary Lysosomes

-Lysosomes merge with a vesicle to form a digestive vacuole -Lysosomes stay fully active by maintaining a low internal pH (by pumping H- ions into their interiors) (hydrolytic enzymes are only maximally active at acidic pH) -Lysosomes that are NOT active = higher pH = more basic --> PRIMARY LYSOSOMES (in a holding pattern)/are inactive -Primary lysosomes will fuse with a vacuole or other organelle, then will start lowering its pH and activating the enzymes *When it becomes ACTIVE, it turns into a SECONDARY LYSOSOME or HETEROPHAGOSOME

Describe MEMBRANE COMPOSITION

-Main components = lipids & proteins -Basic structure = LIPID BILAYER -Provides the basic fluid structure of the membrane & is mostly an impermeable barrier to water-soluble molecules -Individual lipid molecules can diffuse readily throughout their own monolayer -Most membrane proteins span the lipid bilayer and mediate most of the functions of the memb. including transport of molecules across the memb. and ATP synthesis -AMPHIPATHIC (hydrophilic vs. hydrophobic) -Carbohydrates are mainly assoc. w/ PMs where they are chemically combined with lipids to form GLYCOLIPIDS or with proteins to form GLYCOPROTEINS

Eukaryotic: Describe the main functions of the CYTOSOL/CYTOPLASM

-Main site for PROTEIN & HORMONE SYNTHESIS & DEGRADATION, as well as TRANSPORT OUT OF THE CELL -Isolates & eliminates wastes -Metabolic processes -Maintenance of cellular motility -Storage unit for fat, carbohydrate and secretory vesicles -Makes up 55% of the cell's volume -Gelatinous, semi-liquid portion of the cytoplasm -Intermediary metabolism involving enzymatic biochemical rxns -Ribosomal protein synthesis -Excess glucose is stored as glycogen

Eukaryotic: Describe the main components of the General ENDOPLASMIC RETICULUM

-Membrane factory -->Specializes in the synthesis & transport of the protein & lipid components of most of the cell's organelles -Has a network of tubular/saclike channels (CISTERNAE) that extend throughout the cytoplasm and are continuous w/ the outer nuclear membrane (envelope) -The cisternae can be ROUGH (granular) or SMOOTH (agranular)

Eukaryotic: Describe the main components of the MITOCHONDRIA

-Responsible for CELLULAR RESPIRATION & ENERGY PRODUCTION -Surrounded by a double-membrane --> OUTER: smooth & surrounds the mitochon. itself. It is PERMEABLE to many substances. --> INNER: convoluted in the mito. matrix to form CRISTAE increases surface area. Also contains the enzymes of the respiratory chain (ELECTRON-TRANSPORT CHAIN). It is HIGHLY SELECTIVE and has lots of transmembranous transport systems. It also contains a TRANSPORTER to move electrically-charged CALCIUM ions -Metabolic pathways for metabolism of carbs, lipids, AAs, urea, heme, etc. are located in the mitochondrial matrix *Mitochrondria contain their own DNA that codes for enzymes required for oxidative phosphorylation (generates most of the cell's ATP)

What causes LYSOSOMAL STORAGE DISEASES (LSDs)?

-Result of a genetic defect -Lack of one or more lysosomal enzymes

Eukaryotic: Describe the main functions of the ROUGH ER (rER)

-Rough b/c of RIBOSOMES & ribonucleoprotein particles attached to it -Protein synthesis -Process & secretion (ie. pancreatic beta cells secrete insulin) -Some synthesized proteins (by the ribosomes) either stay in the ER, some help make membranes of other organelles (golgi, lysosomes, peroxisomes and nucleus) or of the cell itself -Senses cellular stress* -CHAPERONES facilitate protein folding and prevent the formation of off-pathway types --> Misfolded proteins not repaired in the ER are observed in some diseases and can initiate apoptosis --> Recently shown that the ER mediates intracellular signaling pathways in response to misfolded proteins (Unfolded-Protein Responses (UPR) --> UPR-associated inflammation & ER stress and how it may accelerate age-related dysfunction (current research*) -PROTEIN QUALITY CONTROL

Eukaryotic: Describe the main components of the NUCLEOLUS

-Small & dense -Contains largely RNA, most of the cellular DNA & the DNA-binding proteins (*HISTONES--> bind to DNA and cause it to fold into chromosomes which is essential for cell division in euks) -This is where the genes are copied into RNA and processed -Site of rRNA synthesis

What is Pathophysiology?

-Systemic study of functional CHANGES in cells, tissues & organs that are altered by disease and/or injury -Most importantly: the component of SUFFERING

What is RIBOSOMAL PROTEIN SYNTHESIS?

-Takes place in free ribosomes in the cytosol -Cytosolic ribosomes that make identical proteins are collected in "Factories" known as POLYRIBOSOMES -Excess stored nutrients that are not immediately used for ATP production are converted in the CYTOSOL into their storage forms --> these temporary masses are called INCLUSIONS

Eukaryotic: Describe the main components of the NUCLEAR ENVELOPE

-Two pliable membranes -Pockmarked with pits, called NUCLEAR PORES -Continuous with Rough ER

What are the 4 pathways of degradation in lysosomes?

1) Endocytosis - uptake of macromolecules from ECF 2) Phagocytosis - engulfment of large particles or microorganmisms in phagocytic cells (ie. macrophages, neutrophils, etc.) 3) Macropinocytosis - nonspecific uptake of fluids, membrane and particles attached to the PM 4) Autophagy - (self-eating) begins in the cytosol and is used to digest cytosol and ineffective organelles

What are Sequelae?

Any abnormal conditions that follow and are the result of a disease, treatment or injury

What is a Free Radical?

Atoms, ions or molecules that have at least one unpaired electron -Lone electron pairs/binds with lipids, proteins, DNA, etc resulting in alteration of the structure and function

At the heart of cell bio is _______.

CELLULAR COMMUNICATION / "cellular crosstalk"

Cells become specialized through the process of _________.

DIFFERENTIATION/MATURATION -Cells with some highly specialized function often lack other properties

Protein Transport within a Cell

Gated Transport -selective gates direct the mvmt of proteins & RNA bt the cytosol and nucleus thru NPCs . Protein Translocation -TRANSMEMBRANE PROTEIN TRANSLOCATORS transport proteins across a membrane from the cytosol to a different distinct location -to snake through the translocator, the protein will usually unfold . Vesicular Transport -bubble-like vesicle is a membrane-enclosed intermediate of either a small transport vesicle or a large organelle fragment -discharge their cargo into a diff. compartment by fusing w/ that compartment's membrane . *See Figure 1.14 in text book (p. 102 on pdf) -A sorting signal is required

What is a Reactive Oxygen Species (ROS)?

Highly reactive molecules that contain O2 -Superoxide anion, H2O2, hydroxyl -Neutrophils produce O2 radicals to kill invading pathogens -Hypoxic and ionizing radiation create O2 radicals

All body functions depend on the _______ of cells.

INTEGRITY -cells behave as a multicellular "SOCIAL" organism

________ ________ allow each cell to determine its position and specialized role.

INTERCELLULAR SIGNALS

What is INTERMEDIARY METABOLISM?

Intracellular rxns that include synthesis, degradation & transformation of small organic molecules -Most of the metabolism is accomplished in the CYTOSOL -Enable energy to be used

What is Pompe disease? LSD

Lack of lysosomal alpha-1, 4-glucosidase GAA leads to an accumulation of glycogen in lysosomes resulting in tissue destruction

What causes Age Spots?

Lysosomes: -Indigestible materials are stored in vesicles called RESIDUAL BODIES, whose contents are actively expelled from the cell --> when the materials are lipids, they can remain there for a long time and then get OXIDIZED. This forms a pigmented substance containing polyunsaturated fatty acids & proteins to accumulate in the cell. This pigmented substance is called LIPOFUSCIN, and are called AGE SPOTS in older individuals

Name the main differences between PROKARYOTES vs. EUKARYOTES

PROKARYOTES: -Single-celled -Smaller -No organelles -Nucleus is not bound by a nuclear membrane (MAIN CHARACTERISTIC = LACK OF A DISTINCT NUCLEUS)* -Genetic material in nuclei are in a single, circular chromosome and LACK HISTONES! . EUKARYOTES: -Multi-celled -Larger -More extensive intracellular anatomy/organization -Membrane-bound organelles -Well-defined nucleus -Have several chromosomes -Different structures of RNA/DNA results in differences in protein production -Different mechanisms of transport -Different enzymes

What is Gout? LSD

Undigested uric acid accumulates within lysosomes, damaging the lysosomal membrane -Purines are high in meats and esp. internal organs (liver and kidney) in diets

PROTEOLYTIC CASCADE

*PROTEOSTASIS (proteotome = complete collection of proteins in cells + homeostasis) --> vital to cell health -Tightly orchestrated sequence of events that cause the breakdown of protein Four major cascades -Caspase-mediated apoptosis (cell death) -Blood coagulation cascade -Matrix metalloproteinase cascade -Complement cascade p. 104 on pdf for more about UPS, HSP, ubiquitination, etc.

Eukaryotic: Describe the main components of the PEROXISOMES

-AKA: Microbodies -Have several oxidative enzymes (catalase, urate oxidase, etc.) -Detoxify compounds & fatty acids -Large, oval and irregular in shape -Major sites of OXYGEN UTILIZATION -Contain enzymes that use O2 to remove hydrogen atoms from specific substrates in an oxidative rxn that produces hydrogen peroxide (H2O2) *Catalase (antioxidant enzyme) uses H2O2 to oxidize a variety of other substrates (ie. phenols, formic acid, formaldehyde, alcohol, etc.) by the peroxidative rxn: H2O2 + R1H2 --> R1 + 2H2O -Also have a role in making specialized phospholipids required for nerve cell myelination -Impairment of peroxisomes can lead to disease

Eukaryotic: Describe the primary functions of the NUCLEUS

-Cell division -Control of genetic info -Replication/repair of DNA -Transcription

When cellular fondness/communication breaks down, what happens?

-Cells can adapt (alter function) -Become vulnerable to the isolation and result in injury, disease or even death

Eukaryotic: Describe the main components of the NUCLEUS

-Center of the cell -Largest membrane-bound organelle -Surrounded by cytoplasm on exterior -Surrounded by NUCLEOPLASM on interior --> Chromosomes are suspended in nucleoplasm

Eukaryotic: Describe the main components of the LYSOSOMES

-Membrane-enclosed, sac-like, organelles -Function at an acidic pH (high H- conc.) so they are inactive/on hold at higher (more basic) pH's (less hydrogen) -Filled w enzymes that DIGEST macromolecules and break down intracellular organelles & particles engulfed from outside the cell by endocytosis -Contain > 60 digestive enzymes called HYDROLASES, which catalyze bonds in proteins, lipids, nucleic acids and carbs to their basic components -Function as an intracellular DIGESTIVE SYSTEM -Transport proteins inside the lysosome membrane carry the final basic components to the cytosol where the cell can REUSE OR EXCRETE them *Recent research shows that lysosomes also have established a central role in NUTRIENT-DEPENDENT SIGNAL TRANSDUCTION for cellular ADAPTATION! --> nutrient-sensing metabolic adaptation, quality of proteins and organelles, etc. -Complex transcriptional programs control the synthesis, composition and quantity of lysosomes and reg. their activity to match the evolving needs of the cell -Maintain cellular health bc of efficient removal of toxic cellular components, removal of useless organelles, termination of signal transduction and maintenance of metabolic homeostasis -Aging can lead to progressive loss of lysosomal efficiency and decline or the regenerative capacity of organs & tissues -KEY SIGNALING HUBS - network includes ion and nutrient transporters, protein kinases and phosphatases, transcription factors and transcriptional regulators -The lysosomal membrane acts as a protective shield bt the powerful digestive enzymes within the lysosome and cytoplasm, preventing their leakage into the cytoplasmic matrix (if they leak, CELLULAR SELF-DIGESTION occurs which can lead to lysosomal abnormalities, cellular injury and death)

Eukaryotic: Describe the main components/functions of the SMOOTH ER (sER)

-NO ribosomes/ribonucleoprotein particles . -Membranous surfaces contain ENZYMES involved in the synth. of STEROID HORMONES -->Lipid synthesis, Carbohydrate metabolism, Detoxification (hepatic cells) -Responsible for a variety of reactions required to REMOVE TOXIC SUBSTANCES from the cell* -Communications w the Golgi, lysosomes & peroxisomes

Eukaryotic: Describe the main components /functions of the GOLGI COMPLEX/APPARATUS

-Network of flattened/smooth membranes & vesicles -Located near the nucleus -Receives proteins from ER & packages them into SECRETORY VESICLES --> they collect at the end of the membranous folds of the GOLGI BODIES (CISTERNAE - like a stack of pita breads) -The vesicles break off and migrate to a variety of intra/extra cellular destinations (including PM) -The vesicles fuse with the PM and their contents are released from the cell* -The best-known vesicles are made up of CLATHRIN coats (Clathrin-coated vesicles) --> bud from Golgi complex on the outward secretory pathway & from the PM on the inward endocytic pathway -Newly synthesized ER proteins are carried from the Golgi network to ENDOSOMES by Clathrin-coated transport vesicles before progressing to lysosomes -Many lipids, proteins, glycoproteins, enzymes of lysosomes, etc. pass through the Golgi during maturation (Golgi is a place of refinement and directs the traffic in the cell)

Eukaryotic: Describe the main components of the NUCLEAR PORE COMPLEXES (NPCs)

-Positioned within nuclear pores -Allows molecules to move bt the nucleus and cytosol

Eukaryotic: Describe the main functions of the RIBOSOMES

-Provide sites for protein synthesis -Newly formed ribosomes make a "recognition sequence"/signal (like an address on a written letter) -Signal recognition particles (SRPs) in the cytosol bind to the ribosome after recognizing the SRP . -RIBOPHORINS are the receiver proteins found on the rough ER, and act as the ("address") binding site --> the developing protein threads its way through the ER membrane into the lumen --> the SRP is removed and the new protein chain is folded into its final conformation

Eukaryotic: Describe the main components of the CYTOSKELETON (actin, microtubules & intermediate filaments)

-Provide the "bones and muscles" of the cell (maintains shape and internal organization, permits mvmt w/in the cell and mvmt of external projections (cilia, microvilli, flagella, etc.) -Internal skeleton is composed of a network of PROTEIN FILAMENTS 3 main types: ACTIN (MICROFILAMENTS) -smaller fibrils that occur in bundles -conc. in cell's CORTEX, just beneath the PM -major facilitator for many cell func's including movement, endocytosis, maintenance of a cell and tissue shape -link the interior of the cell to adjacent cells through CELL JUNCTIONS -necessary for regulating cell growth & drive the pinching of one cell into 2 . MICROTUBULES - small, hollow, cylindrical, unbranched tubules made of protein -exhibit rigidity (add strength to cell's structure) -support/move organelles -facilitate transport of impulses along neurons -have roles in inflammatory & immune responses and hormone secretion -arranged in the thickened base (BASAL BODY) of a protrustion from the cell's PM . INTERMEDIATE FILAMENTS -braided, ropelike fibers made of several filament proteins - . *Collectively promote cell strength, shape and movement *The diff. filaments form a mesh called the NUCLEAR LAMINA beneath the inner nuclear memb., creating a protective chamber for the cell's DNA *In epithelial tissue, these fil's bridge the cytoplasm from one cell junc. to another, supporting and strengthening the sheet of epithelium . -Also involved with the extracellular matrix and nuclear interior in FORCE TRANSMISSION (mechanical forces) called MECHANOTRANSDUCTION

Eukaryotic: Describe the main components of the RIBOSOMES

-RNA-protein complexes (nuceloproteins) -Made in the nucleolus & secreted into the cytoplasm through NPCs -Can float freely in cytoplasm or can attach to outer membranes of the ER

What are the main functions of proteins? (major workhorses of the cell)

-Receptors -Transporters -Enzymes -Surface markers -Cell adhesion molecules (CAMs) (proteins that allow cells to hook together and form attachments to the cytoskeleton for maintaining cellular shape) -Catalysts *see p. 103 on pdf

Cell-to-Cell Adhesions

1) The Extracellular Matrix -Basement Membrane/Basal Lamina --> very thin, tough & flexible --> lies beneath epithelial cells -The ECM is like glue, but also provides a pathway for diffusion of nutrients, wastes, etc. bt blood and tissue cells -Major functions: mechanical support, control of cell proliferation, formation of a scaffold for tissue regeneration, establishment of tissue microenvironments -Collagen, Elastic, Fibronection, etc. p. 109-112 pdf . 2) Cell Adhesion Molecules in the PM -Cell surface proteins that bind the cell to an adjacent cell and to the ECM -4 protein families: -Integrins - receptors that regulate cell-ECM interactions w collagen, elastin, etc. . -Cadherins - Ca++ dependent glycoproteins and have a unique pattern of tissue distribution . -Selectins - bind certain carbs (ie. mucins) . -Immunoglobulin superfamily CAMs (IgSF CAMs) -- bind integrins or other IgSF CAMs p. 112 . 3) Specialized Cell Junctions -Cells in direct physical contact with neighboring cells are linked at specialized regions of their PMs called CELL JUNCTIONS which are classified by their function (see p. 113 for specifics) -Overall, making epithelium leak-proof, allowing communication tunnels and maintaining cell polarity p. 114 for more info

What is Tay-Sachs disease? LSD

Accumulation of GM2 ganglioside (a lipid) in lysosomes as a result of a deficiency/absence of lysosomal hexosaminidase A (HEXA) *HEXA plays a critical role in the brain and spinal cord to break down fatty substance GM2 ganglioside

What are Clinical Manifestations?

Signs & Symptoms

What is Mechanotransduction?

The cellular processes that translates mechanical stimuli into biochemical signals, allowing cells to adapt to their surroundings.

Describe the changes in theories about the lipid bilayer over the last few years.

Used to be: FLUID MOSAIC -a fluid lipid bilayer composed of a uniform lipid distribution with inserted, moving proteins . Is now: MICRODOMAINS -lipids and proteins are not evenly distributed but can isolate into microdomains, differing in their protein and lipid composition ie. LIPID RAFTS (dynamic domain structures composed of cholesterol, sphingolipids, and membrane proteins) -Many lipids and proteins are not distributed uniformly but are seen to concentrate in a TEMPORARY, dynamic way assisted b protein-protein interactions that enable transient formation of DOMAINS or lipid rafts -Larger assemblies of clusters are called CAVEOLAE which are flask-shaped invaginations thought to form from lipid rafts and to be important for endocytosis . 3 major phases of lipid bilayer organization: 1) SOLID GEL PHASE (low temperatures) 2) LIQUID-ORDERED PHASE (high temps) 3) FLUID LIQUID-CRYSTALLINE (or liquid-disordered) PHASE