Week Three Objectives Flashcards

Question

Describe Glycogen Structure

Answer 1

Glycogen is a polymer of glucose Two types of carbon carbon bonds in glycogen (1: 4) linear chains (1: 6) make branch points Glycogen syntase adds UDP-glucose to chain until 11 units long Branching enzyme cleaves a piece of chain off and attaches it in a 1:6 glycosidic linkage- both braches are further extended

Answer 2

Glycogen is used as a glucose storage for most cell types In heart & Skeletal- intracellular glucose buffer, buffer for glucose 6-phosphate for use within cells (depends on how much getting from blood, and how much cell is doing). When cleaving glycogen its use is for ONLY that cell Liver- Serves as glucose buffer for BLOOD, regulates whole body glucose homeostasis. Used for hepatocyte but is also excreted in blood

Answer 3

Glycogen Synthase- adds UDP glucose on to glycogen core 4:6 transferase (branching enzymes) cleaves a piece of chain off and attaches it in a 1:6 glycosidic linkages Both branches extended

Answer 4

Increases solubility Make more active ends so glycogenolysis and glycogenesis can happen rapidly

Answer 5

Glycogen phosphorylase- cleaves unites of glucose from glycogen chains and adds inorganic phosphate to make glucose-1-phosphate (but can't cleave glucose with in four units of branch point) Debranching enzyme- two activities (4:4 transferase activity) cleaves a 1:4 bond and transfers 3 glucose units to the end of another chain in 1:4 bond (alpha-1,6-glucosidase activity) hydrolyzes the remaing glucose's 1:6 bond to release glucose

Answer 6

In Fed State: both are UNphosphorylated, glycogen phosphorylase is inactive, glycogen synthase is active In Fasted State: both are PHOSPorylated, glycogen phosphorylase is active, glycogen synthase is inactive

Answer 7

Insulin activates (phosphorylates) protein phosphatase-1 which dephosphorylates glycogen synthase (activating it) Inhibits (phosphorylates) glycogen synthase kinase-3 (inactiving it)

Answer 8

cAMP --\> PKA --\> phosphorylates glycogen synthase (inactive) and glycgoen phosphorylase kinase (active) --\> which then phosphorylates glycogen phosphorylase (acitve) --\> glycogenolysis --\> GLUCOSE

Answer 9

No glucagon receptor Nerve impulse--\> Ca --\> Ca/calmodulin dependent kinase --\> phosphorylates glycogen phosphorylase kinase --\> phosphorylase glycogen phosphorylase (active) Work --\> AMP --\> AMPkinase --\> glycogen phosphorylase kinase (active) --\> glycgoen phosphorylase (active) Insulin --\> phosphorylates protein phosphatase-1 (active) and glycogen synthase kinase 3 (inactive) --\> protein phosphatase then dephosphorylates glycogen synthase (active)

Answer 10

mutation/ deficiency in glycogen synthase Normal glucose tolerance, variable clinical presentation of exercise intolerance, cardia and muscle hypertrophy

Answer 11

deficiency in glucose 6- phosphatase (can't make all the way back into glucose to leave cell) Fast hypoglycemia, lactic acidosis hepatomegaly due to glycogen accumulation hyperuricemia and hyperlipidemia Treatment: avoid fasting by frequent feeding, uncooked cornstarch

Answer 12

Deficiency of 1,6-glucosidase activity of debranching enzyme \*can make glycogen when eating too many carns, but can't break it down all the way in fasting state GSD IIIa : affects liver and muslce GSDIIIb: only affect liver Symptoms: fasting hypoglycemia, ketoacidosis, hyperlipidemia, heptomegaly with high ALT/AST Treatment: frequent high carb meals

Answer 13

mutation in 4:6 transferase activity of branching enzyme, longer than normal brances, liver failure FATAL

Answer 14

mutations in muscle glycogen phosphorylase late childhood onset of exercise intolerance, myoglobinuria after exercie Increased creatine kinase, exaggerated increase of creatine kinase and ammonia after exercise (can't utilize glycogen, swithcing to AA metabolism) Avoid exercise

Answer 15

* Genome- ssRNA, dsRNA, ssDNA, dsDNA * Capsid- protein coat around genome (capsomere), protects nucleic acids, and is responsible for binding host cells if not enveloped * Envelope- (some, not all viruses) glycoproteins, function is to bind and mediate entry into host cells. “Naked viruses” have no envelope * Tegument- space between capsid and envelope, protein dense region that surrounds capsid, holds them together * Virion- infectious particles produced

Answer 16

• Latent period- externally doesn’t seem like anything is happening, but really transcription/ translation/replication are occurring o Good period for attack * Then get rapidly release of virions in ONE STEP (lots of viruses at ONE time) * Those virions can go off and affect other cells

Answer 17

* Plaque Assay- one of the most accurate ways to measure virus infectivity and infectious viral particle numbers * Procedure o Mixture containing molten top agar, bacterial cells, and diluted phage suspension o Pour mixture onto solidified nutrient agar plate o Let solidify, sandwhich of top again and nutrient agar o Incubate o Results are phage plaques on a lawn of host cells

Answer 18

* Transformation- virus transforms cell into tumor cell * Lysis- death of cell and release of virus * Persistence- Slow release of virus without cell death * Latent- virus present but not replicating * Reactivation- may revert to lytic infection? * Cell fusion- didn’t go over?

Answer 19

* Temperate virus- can go lytic or lysogenic? * Lysis- viral DNA replicates, coat proteins synthesized, virus particle assembled, host cell is lysed open to expose contents * Lysogeny- viral DNA is integrated into host DNA, lysogenized cell under goes cell division replicating the prophage (integrated genome) * Prophages conferring virulence factors

Answer 20

dsDNA (+) genome classical semiconservative replication Example: Herpres virsues- uses host DdRp to make mRNA

Answer 21

ssDNA (+) genome dsDNA intermediate classical semiconservative, discard (-) strand for packaging

Answer 22

dsRNA (+) genome transcription of minus strand to make (+) strand

Answer 23

ssRNA (+) genome (can be used directly as mRNA) makes ssRNA (-) and transcribes this to give ssRNA (+) genome Example: Polio/ Picornaviruses \*needs RdRp, so must do some translation before genome replication one long ssRNA strand gets cut after translation into individual proteins

Answer 24

ssRNA (-) genome makes ssRNA (+) and transcribes this to give ssRNA (-) genome Example: Influenze/ orthomyoxyviruses ssRNA (-) released into cytoplasm, transported to nucleous to steal caps and stuff brings RdRp with it (attached to each segment of genome)

Answer 25

ssRNA (+) genome transcribes (-) strand of dsDNA to replicate genome (Reverse transcription) Example: Retroviruses/ HIV two copies of ssRNA (+) genome, plus RT and integrase in virion integrase intergrates dsDNA into host genome

Answer 26

dsDNA genome transcription followed by reverse transcription

Answer 27

Attachment/adsorption Penetration/ injection Synthesis of nucleic acid and protein Assembly and packagine Release

Answer 28

* Selective Toxicity- antibiotics need to injure the invading organism while causing minimal adverse effects to the host * Toxicity- can be due to o Extension of mechanism of action • Trimethoprim can inhibit folate metabolism in humans as well as bacteria resulting in bone-marrow o Unintended consequences • Vancomycin can stimulate histamine release (red man syndrome) o Impaired drug metabolism • Renal failure or hepatic insufficiency result in direct antibiotic effects or drug interaction

Answer 29

* Prophylactic- treating individuals at a high risk of developing an infection to prevent an infection from developing * Pre-emptive- lab test indicate organism is present but patient is not symptomatic * Definitive Therapy- pathogen identified (monotherapy, narrow spectrum) * Suppressive Therapy- after initial disease is controlled, therapy is continued to prevent recurrence

Answer 30

* Bacteriostatic- limits growth and if removed the organism can grow again. Usually successful because allows immune system to catch cup * Bactericidal- 99.9% reduction in bacterial inoculums with 24 hr period of exposure * \*\*many bactericidal drugs do not work well if the cells are not actively diving * \*\* persons with depressed immune systems would not be good canidates for bacteriostatic drugs

Answer 31

* absorption- movement of drug into vascular system, variability in how well drugs are absorbed from the gut * Distribution- transfer of drug from vascular system to tissue * Metabolism- transformation of a compound into metabolites (liver) often inactivates or eliminates the drug BUT prodrugs become active * Excretion- removal of the drug from the body through urine or feces

Answer 32

* Intrinsic resistance- absence or inaccessibility of the target of the drug action * Acquired drug resistance- genetic variability exists in the population and resistant forms are able to preferential grow in the presence of the antibiotic o Variability may result from errors during replication o Transformation of external DNA o Bacteriophage can introduce new DNA through transduction o Conjugation- transfer of R plasmid containing several resistance determinant genes

Answer 33

i. Cell wall synthesis (peptidoglycan) ii. Nucleic acid synthesis iii. Cell membrane integrity iv. Metabolic pathways (folate biosynthesis) v. Protein Synthesis

Answer 34

Acquired Drug Resistance- genetic variability exists in the population and resistant forms are able to preferential grow in the presence of the antibiotic \*\*UNDERSTAND DRUG ITSELF IN NOT CAUSING RESISTANCE\*\* ## Footnote a. Drug enters cell but efflux pump ejects it b. Drug-inactivating enzyme- enzyme modifies drug that inactivates it c. Alteration in target molecule d. Decreased uptake

Answer 35

phosphoribosyl amidotransferase transfers an amine from glutamine to PRPP Add glycine to make glycinamide ribosyl 5-phosphate Carbon, nitrogen are added from THF, CO2, glutamine, and aspartate to form inosine monophosphate (IMP) To make AMP, asaprtate bonds to IMP --\> adenyloscuccinate, then fumarate is cleaved off to make AMP To make GMP, IMP is oxidized to xanthine monophophate. Amine group is transferred from glutamine. AMP and GMP are phosphorylated to make adenosine triphosphate and guanosine triphosphate

Answer 36

1. Toxicity- producing toxins 2. Host immune response- repsonse of the host to bacteria 3. Colonization/ proliferation

Answer 37

Exotoxins- not part of the structure, released into enviornment: heat labile, specific mode of action, high toxicity, highly immunogenic Endotoxins- integeral part of the structure itself, not excreted (Example- LPS): heat stable, general mode of action, low toxicity, poor immunogen, induces fever

Answer 38

Physical Barrrier- skin, mucous, epithelial layers, normal flora etc. Innate Immune System- recognizes forgien particles non specifically, mediated by phagocytosis, recognizes PAMPs, complement, interferons (dendritic cell, marcophage, neutrophil, mast cell) Adaptive Immune System- inducible, needs to learn how to recognize specific pathogens, has memory, takes time to develop (Antigen, BCR, antibody, TCR)

Answer 39

Exotoxin, makes holes in membranes surrounding cell. Cause efflux of cytoplasmic components, influx of extracellular components

Answer 40

Hemolysins- type of cytolytic toxin that affects redn blood cell EXAMPLE: STREP 1. Alpha hemolytic- produces hemolysins that damages but doesn’t destroy red blood cells EXAMPLE: STAPH 2. Beta hemolytic- produces hemolysins completely destroys red blood cells 3. Gama hemolytic- does not produces hemolysin

Answer 41

- Exotoxin, proteins excreted with two different modes of action, b = binding, a = activity 1. B domain binds to surface of susceptible cells, stays on outside 2. A domain gets released into cytoplasm and shuts down something inside cell (shut down EF-2, which stops all protein synthesis) EXAMPLES: E. COLI, Corynebacterium diphtheriae

Answer 42

exotoxin, secreted into small intestine, causes diarrhea

Answer 43

Exotoxin that can block release of excitation signal, (flaccid paralysis) or binds to inhibitory interneurons preventing release of glycine and relaxation of muscle (Tetanus- rigid paralysis)

Answer 44

Exotoxin, foreign molecule that can exploit interaction between T-cell receptor and MHC class II molecules. Links T-cell and MHC class II receptors NON-SPECIFICALLY activates A LOT of T-cells, causes runaway massive whole body inflammation EXAMPLE: STAPH

Answer 45

prophage confers additional virulence genes to bacteria

Answer 46

bone marrow cell myeloid precursor monocyte/granulcytes Dendritic cell, macrophage, neutrophil, mast cells (these sells have PRRs that recognize PAMPs)

Answer 47

Bone marrow stem cell lymphoid precursor B cell/ T cell B Cells can divide into plasma cells (produce antibodies) and memory cells

Answer 48

serum proteins, overall goal is to control inflamation Microorganism can spontaneously activate complement, results in opsonizaiotn and facilited up take of the coated microogranisms by phagocytes.

Answer 49

1. Enterotoxin (diarrhea) (type of exotoxin excreted into small intestine) 2. Type 1 Fimbriae (enhances edherence) 3. Endotoxin in LPS layer (fever)- inherent of gram neg 4. Injectosome- ticks phagasome to take it into the cell 5. Siderophores- gets excreted into near surface environment and takes up Fe (steals Fe from cells) ramps up ability to utilize more complex metabolic pathways 6. Anti-phagocytic proteins induced by oxyR- prevent degredation by phagosomes 7. O antigen (inhibits phagocyte killing) 8. Cytotoxin (inhibits host cell protein synthesis, calcium efflux, adherence) 9. Flagellum (motility) 10. H Antigen (adherence, inhibits phagocyte killing) 11. Vi capsule antigen- inhibits complement binding

Answer 50

RECOGNITION AS FORGIEN PARTICLE * During replication Hep C makes a dsRNA intermediate. * This dsRNA molecule is recognized by TLR3 a Toll-like receptor (PRR) * The dsRNA binds to TLR3, which activates a signaling cascade, * Downstream IRF3 is phosphorylated, which forms a dimer and is transported to the nucleus * IRF3 acts as a transcription factor for IFNB (interferon)? * IFN-B protein turns on genes that set up an anti-viral state (i.e, shuts down metabolic pathways viruses need to survive, and slows down infection so immune system can catch up. BACK UP PLAN * If virus gets past TLR3, dsRNA can bind to RIG-I which binds MAVS, which activates NFkB → IFN-beta * INTRACELLULAR INNATE IMMUNE RESPONSE BYPASS • Viral protein NS3/4A cleaves viral protein, but also destroys signaling pathway proteins so can’t produce interferon → don’t get intracellular innate immune response/ antiviral state

Answer 51

* Small protein, important in cell signaling, limit the spread of viral infection by the INNATE system * Type 1 interferons- are produced by cells that have become infected with a virus * Typer 2- released by activated T

Answer 52

1. Cytopathic effect: viral infection disrupts normal cell physiology 2. Host immune response: response of the host to the virus casues illness 3. Tumorigenesis: viral infection promotes uncontrolled proliferation of infected cells

Answer 53

1. Overgrowth: spread of fungal infection is significant in the cause of illness 2. Host immune response: response of the host to the fungus casues illneess

Answer 54

1. Displacement: tissure displacement/ obstruction due to the growth of protozoa causes illness 2. Cytpoathic effect- intracellular protozoa infection disrupts normal cell physiology 3. Host immune response: response of the host to protozoa causes illness

Answer 55

1. Displacemnt- tissue displacement/ obstruction due to the growth of helminth causes illness 2. Parasite/ Competition: helminth consumes host nutrition 3. Host immune response: response of the host to protozoa csuses illneess