Dr. White-Molecular and Biochemical Basis of Disease Flashcards
what are the functions of the cytoskeleton?
bones of the cell
important in organization of the cell
maintains correctly shipped cells
insures cells are properly structured internally
What are the three families of cytoskeletal proteins?
actin filaments
microtubules
intermediate filaments
What do actin filaments do?
(mardi gras beads)
determine the shape of cell’s surface and are necessary for whole cell locomotion, secretion, endocytosis
What do microtubules do?
(slinky of life)
forms tube like structure and determine the position of membrane enclosed organelles, directs intracellular transport
What do intermediate filaments do?
(like girders in building or highway)
provide mechanical strength, resists mechanical stress, allows formation of hair and fingernails
What are actin subunits used for?
assembly of actin filaments, form helical assembles of subunits
Actin filaments are arranged in ______ structure
head to toe
Actin monomers contains a binding site for ____
ATP (or ADP)
What are tubule subunits used for?
formation of microtubules
Tubulin is a heterodimer of _____ and _____ with noncovalent bonds
alpha tublin and beta tubulin
Both alpha and beta tubulin have binding sites for ____
GTP
If cytoskeleton of RBC is defective it can lead to the diseased called hereditary spherocytosis (HS) , which causes what?
RBCs spherical not bi concave, fragile red blood cells burst resulting in hemolytic anemia
What is spectrin?
part of the RBC cytoskeleton
attaches to membrane, and is defective in HS
What is the clinical presentation of HS?
hemolysis, anemia, splenomegaly
What is listeria?
pathogenic bacteria that invade your intestinal cells and can cause serious infection
What are the symptoms of listeria?
headache, stiff neck, confusion, loss of balance, and convulsions in addition to fevers and muscle aches
How does listeria cause illness?
attaches to receptors on enterocytes, enters and replicates in your intestinal cells. Unusual behavior is based on the actin cytoskeleton and accessory proteins
Describe Duchenne muscular dystrophy (DMD)
most common fatal neuromuscular disorder
severe, progressive muscle degeneration
loss of ability to walk (wheelchair bound by 12)
loss of lung and cardiac function, scoliosis
premature death in 20s and 30s due to respiratory failure or cardiomyopathy
What is the treatment for DMD?
no medical treatment to alter course of disease, but treatment for patients general health and quality of life
glucocorticoids (prednisone) slow the decline in muscle strength but he effect is relatively short and does not alter clinical course of disease
DMD is X linked ____ and caused by which gene mutation?
recessive, dystrophin gene mutation
What is the main function of the dystrophin protein?
provide structural stability to the muscle cell membrane during cycles of contraction and relaxation
What are the functional domains of the dystrophin protein?
- n-terminus (actin binding domain)
- long spectrin like repeat domain: cytoskeletal portion of the dystrophin protein
- cysteine rich and C-terminus domains
What is the clinical presentation of DMD?
dystrophic myopathy: progressive muscle degeneration with loss of functional muscle tissue over time with resulting weakness
elevated creatine kinase in blood: 50 to 100 times normal (over 1,000 U/L)
slow walking, general weakness
mean age of diagnosis : 4 years, 10 months
wheelchair by age 12/13
What is pseduohypertrophy?
replacement of muscle with adipose and fibrous connective tissue- enlarged calves
What is lordosis?
excessive inward curvature
what is kyphosis?
upward back curvature outward
Describe Becker muscular dystrophy (BMD)
milder form
loss of walking after 16 years
muscle pain, dilated cardiomyopathy
increased workload on left ventricle leads to ventricular enlargement, severity results in heart failure and death
DMD lacks what protein? What is the difference in this vs BMD?
DMD lacks dystrophin protein
BMD has some dystrophin protein but abnormal quantity and size
What is the function of mitochondria?
provide cellular energy in the form of ATP for the cell
What is mitochondrial myopathy?
muscle disease caused by mitochondrial dysfunctions
Are mitochondria maternally or paternally inherited?
maternally
What is heteroplasmy?
when there is a mtDNA mutation: there is a mixture of normal mitochondria and mutant mitochondria
there is a threshold–too much mutant mitochondria, disease will occur
What tissues are affected by mitochondrial disease?
brain/CNS, heart, skeletal muscles
Describe MERRF
-myoclonus: often the first symptom, involuntary muscle jerking
- myoclonic epilepsy
- ataxia
- ragged red fibers
- seizures, dementia
90% of mutations caused by 2 mutations of tRNAlys
What are the main mutations of the tRNAlys in MERRF?
85% due to A to G mutation in the mtDNA tRNAlys gene at nucleotide portion 8344
5% due to G to C at position 8356 in tRNAlys mtDNA gene
Describe MELAS
-seizures
-blindness
- headaches
-anorexia
- recurrent vomiting
- lactic acidosis
- ragged red fibers
age of onset : 2-10 years
Describe Kearnes-Sayre Syndrome (KSS)
onset before age 20
-retinitis pigementosa
at least one of the following: cardiac conduction abnormality, cerebellar ataxia, cerebral spinal protein level above 100 mg/dL
ragged red fibers seen in skeletal muscle
describe CPEO
mild to moderate mt myopathy- mtDNA rearrangments
ptosis
describe LHON
mt mutation only affects optic nerve
no muscle involvement
acute or subacute, bilateral, central vision loss
degeneration of the retinal ganglion cell layer and optic nerve
age of onset: 20 to 30s
mtDNA mutatie in coding genes of complex I proteins
What are the functions of erythrocytes?
transport oxygen forms the lungs to the tissues
hemoglobin occupies ____ percent of the volume of erythrocytes and _____ percent of the cells dry weight
33, 90
what is tissue switching?
switch phenomenon as to where red blood cells are made during development (around birth)
What is the structure of hemoglobin?
2 alpha globin chains, 2 beta globin chains
one heme per subunit that has iron that carries O2
four protoporphyrin IX rings
What are the three types of hemoglobin in humans?
embryonic, fetal and adult
What are the four types of globin chain in adult hemoglobin?
alpha, beta, delta, gamma
What is the predominant form of hemoglobin in adults?
HbA which has 2 alpha and 2 beta subunits
What are the alpha like chains of hemoglobin?
zeta embryonic and alpha
What are the beta like chains of hemoglobin?
epsilon embryonic, gamma fetal, delta, beta
How does HbS (sickle cell anemia) occur?
aa switch in position 6 in Beta globin of valine for glutamic acid
Why does O2 flow from mother to fetus?
HbF does not bind well to 2,3 BPG and therefore has higher affinity for O2
