Disorders week 1

Question 1

progeria

• type of mutation
• protein involved
• effect
• prognosis

Answer 1

• first success of the human genome project
• point mutation causing and unusable form of lamin A
• nuclear lamin cannot be formed properly
• age quickly and only live into their teens

Question 2

restrictive dermopathy

• genetic inheritance
• gene involved
• effect

Answer 2

• autosomal recessive
• loss of a gene that is responsible for the cleavage of pre-lamin into mature nuclear lamin
• skin does not grow and the child suffocates in own skin

Question 3

Huntington’s disease

• effect of genetic change
• genetic change to the gene
• significance in cell bio
• determinant of severity
• determinant of age of onset

Answer 3

• brain cell nuclei show a high level of the protein huntingtin, which is typically found in the cytoplasm
• the accumulation of this protein disturbs nuclear function
• defect in gene is caused by an accumulation of an unnatural amount of trinucleotide repeats
• Relevance in cell bio is that this protein got into an area of the cell that its not supposed to via a mechanism probably having to do with the conformation of the protein (trinucleotide repeat is not an NLS)
• severity of the disease is correlated with how much huntingtin protein is found in the nuclei
• age of onset is correlated with the number of trinucleotide repeats

Question 4

Cancer and exportin 1

Answer 4

• exprotin 1 is responsible to removing tumor suppressing proteins from the nucleus so the cell is able to divide
• in some cancerous cells, exporting 1 expression is increased, causing there to be a greater removal of tumor suppressing TF’s etc.
• several small molecule inhibitors of this protein have been developed and are now in stage 2 clinical trials

Question 5

Tay-Sachs

• classification
• gene involved
• effect
• build up of what
• symptoms

Answer 5

• Lysosomal storage disease
• deficiency in hexosaminidase A
• disrupts sphingolipid breakdown
• results in the buildup of GM2 ganglioside
• causes mental retardation, blindness, and early death

Question 6

Fabry’s

• classification
• gene involved
• build up of what
• symptoms
• treatment

Answer 6

• lysosomal storage disease
• alpha galactosidase A deficiency
• results in build up of ceramide in lysosomes
• rash on the inner lip/tongue and kidney failure
• treated with enzyme replacement therapy

Question 7

Gaucher’s disease

• classification
• treatment

Answer 7

• lysosomal storage disesae

- also treated with enzyme replacement therapy

Question 8

niemann-pick

-classification

Answer 8

lysosomal storage disease

Question 9

GM1 gangliosidosis

-calssification

Answer 9

-lysosomal storage disease

Question 10

Asthma/Anaphylaxis

• molecules which cause symptoms
• classification of this molecule

Answer 10

• are induced by leukotrienes which cause vasodilation and bronchoconstriction in asthma/anaphylaxis
• a membrane lipid called and eicosanoid

Question 11

mycoplasma (walking) pneumonia

• prevalence
• cause
• cellular pathology
• symptoms
• perpetuation

Answer 11

• most common form of pneumonia
• caused by an increase in the fluidity of ciliated cells in the lungs
• mycoplasma burrows down to the root of the cilia where is feeds on the cholesterol of the plasma membrane
• causes the cilia not to beat properly
• results in mucus accumulation in the respiratory tract, creating a favorable environment for the mycoplasma

Question 12

HIV

• mechanism of infection
• cellular consequences of infection with regards to membranes
• class significance

Answer 12

• takes advantage of the fusogenic nature of plasma membranes
• HIV has a viral glycoprotein that is recognized by the CD4 receptor on T cells, macrophages, and other cell types
• when HIV binds, there is rapid fusion of the membrane, spilling HIV nucleic acid into the cell and the viral membrane is incorporated in the cells
• incorporation of the membrane allows infected cells to fuse with other CD4+ cells, resulting multinucleated cells are incapable of carrying out their immune function
• glycoproteins allow for entry and those glycoproteins then allow other cells to fuse, demonstrating the fusogenic property of cell membranes

Question 13

Measles

• mode of action
• similar to
• propogation
• class significance

Answer 13

• takes advantage of fusogenic properties of phospholipids
• same as HIV
• infected cells can fuse with healthy cells, propagating the virus
• fusion of cell membranes

Question 14

Toxoplasmosis

• class of organism
• found where
• mode of action
• class significance

Answer 14

• protozoan found in cat feces
• causes severe birth defects in unborn children
• binds to certain cells in the body based on the glycoproteins of those cells
• shows a clinical significance of glycoproteins

Question 15

Coccidiosis

• classification of organism
• found where
• mode of action
• class significance

Answer 15

• protozoan that can live in the water and food source of developing countries
• binds to glycoproteins of cells in the GI tract
• the composition of glycoproteins on the cell surface changes as you move down the GI and different strains of this protist latch on to different areas
• you can tell which type of coccidiosis it is by where the pain is and in turn this can help public health professionals identify the problem
• another example of clinical glycoprotein problems

Question 16

Cystic Fibrosis

• cause, gene involved
• classification of gene product
• mechanism
• cell bio sig

Answer 16

• caused by a mutation in the CFTR protein, which is an ABC ATPase
• without this protein being functional, Cl- transport across the membrane can not be regulated.
• cell biology: defects in an ABD ATPase

Question 17

Tangier disease
-cause and protein involved
-mechanism
-prognosis
-research of this disease has led to
-

Answer 17

• Caused by a defect in ATP Binding cassette 1, another ABC ATPase
• can not shuttle cholesterol out of the cell due to a defect in this transporter
• without cholesterol to pick up, HDL is quickly cleared from the plasma causing an HDL deficiency and a build up of cholesterol in the vessel wall
• results in premature coronary heat disease CHD
• usually die in 40s or 50s due to CHD
• study of this disease have identified mechanisms of reverse cholesterol transport and the roles of HDL and LDL in the body
• this is a disorder caused by a defective ABC ATPase, ATP binding cassette 1

Question 18

P glycoprotein/MDR complex in cancer

Answer 18

• These are the same thing and is are an ABC ATPase that is capable of pumping out toxins
• to treat cancer we often use toxic drugs, however there is a problem when this protein is overexpressed in cancer cells and the cells are capable of shuttling out all of the drug so it can not take effect
• another ABC ATPase disorder

Question 19

familial hypercholesterolemia

• due to
• genetic inheritance
• homozygote symptom
• 3 defects found to cause this
• these problems all lead to
• class significance

Answer 19

• due to defective receptor mediated endocytosis
• autosomal dominant disease
• homozygotes have extremely elevated cholesterol and die of cardio problems before 30’s
• seferal defects found: failure of LDL to bind properly to the receptor,failure of receptor to clutter into coated pits, mutant receptor that missing the membrane spanning segment causing abnormal binding and eventual secretion
• all of these problems result in increased blood cholesterol and lead to arteriosclerosis
• defective endocytosis

Question 20

rabies, influenza

• mode of entry
• cell bio significance

Answer 20

• both use receptor mediated endocytosis to enter the cell

- endocytosis gone wrong

Question 21

streptococcus

Answer 21

• second most common bacterial pathogen in humans

- has a carb coat on cell surface which macrophages do not recognize and therefor can not phagocytose

Question 22

legionnaires disease

• organism that causes it
• mechanism of action
• cell bio sig

Answer 22

• L. pneumophila, a bacterium, is the cause
• it is phagocytes by the epithelial cells of the respiratory tract
• once inside the phagosome, it quickly neutralizes the environment so the phagosome can not fuse with the lysosome to form thee phagolysosome
• then proliferates
• this is an example of a phagocytosis problem

Question 23

Leishmania and leprosy

• orgnisms that cause each
• mechanism of action
• cell bio sig

Answer 23

• protozoan causes leish and mycobacterium causes pep
• these organisms thrive in the acidic environment of the phagolysosome and multiply
• these utilize phagocytosis to their advantage

Question 24

I cell disease

• cause
• protein affected
• mechanism
• cell bio sig

Answer 24

• accumulation of a variety of polymers in the lysosome and highly elevated secretion of lysosomal enzymes
• this is caused by a dysfunctional N-acetylglucosamine phosphotransferase, which is responsible for making the phsopho-mannose that acts as a signal for enzymes to target the lysosome
• studying this lead to the discovery of the lysosomal protein targeting system
• since there is no signal, the proteins are excreted by default and the lysosomes are free of enzymes
• this is a problem with protein targeting

Question 25

mucopolysaccharidoses 1-4

Answer 25

• most common of the LSD’s

- lysosomes become engorged with mucopolysaccharides (glycosaminoglycans)

Question 26

zellwegger syndrome and neonatal adrenoleukodystrophy (NALD)

Answer 26

• these two diseases are due to mutations in the SKL signal that sends proteins to the peroxisomes
• this results in the proteins destined for the peroxisomes never make it there and the peroxisomes do not function properly

Question 27

Infantile hypoglycemia

Answer 27

-also caused by an ABC-type ATPase