Dr. White-Molecular and Biochemical Basis of Disease

Question 1

what are the functions of the cytoskeleton?

Answer 1

bones of the cell
important in organization of the cell
maintains correctly shipped cells
insures cells are properly structured internally

Question 2

What are the three families of cytoskeletal proteins?

Answer 2

actin filaments
microtubules
intermediate filaments

Question 3

What do actin filaments do?

Answer 3

(mardi gras beads)

determine the shape of cell’s surface and are necessary for whole cell locomotion, secretion, endocytosis

Question 4

What do microtubules do?

Answer 4

(slinky of life)

forms tube like structure and determine the position of membrane enclosed organelles, directs intracellular transport

Question 5

What do intermediate filaments do?

Answer 5

(like girders in building or highway)

provide mechanical strength, resists mechanical stress, allows formation of hair and fingernails

Question 6

What are actin subunits used for?

Answer 6

assembly of actin filaments, form helical assembles of subunits

Question 7

Actin filaments are arranged in ______ structure

Answer 7

head to toe

Question 8

Actin monomers contains a binding site for ____

Answer 8

ATP (or ADP)

Question 9

What are tubule subunits used for?

Answer 9

formation of microtubules

Question 10

Tubulin is a heterodimer of _____ and _____ with noncovalent bonds

Answer 10

alpha tublin and beta tubulin

Question 11

Both alpha and beta tubulin have binding sites for ____

Answer 11

GTP

Question 12

If cytoskeleton of RBC is defective it can lead to the diseased called hereditary spherocytosis (HS) , which causes what?

Answer 12

RBCs spherical not bi concave, fragile red blood cells burst resulting in hemolytic anemia

Question 13

What is spectrin?

Answer 13

part of the RBC cytoskeleton

attaches to membrane, and is defective in HS

Question 14

What is the clinical presentation of HS?

Answer 14

hemolysis, anemia, splenomegaly

Question 15

What is listeria?

Answer 15

pathogenic bacteria that invade your intestinal cells and can cause serious infection

Question 16

What are the symptoms of listeria?

Answer 16

headache, stiff neck, confusion, loss of balance, and convulsions in addition to fevers and muscle aches

Question 17

How does listeria cause illness?

Answer 17

attaches to receptors on enterocytes, enters and replicates in your intestinal cells. Unusual behavior is based on the actin cytoskeleton and accessory proteins

Question 18

Describe Duchenne muscular dystrophy (DMD)

Answer 18

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

Question 19

What is the treatment for DMD?

Answer 19

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

Question 20

DMD is X linked ____ and caused by which gene mutation?

Answer 20

recessive, dystrophin gene mutation

Question 21

What is the main function of the dystrophin protein?

Answer 21

provide structural stability to the muscle cell membrane during cycles of contraction and relaxation

Question 22

What are the functional domains of the dystrophin protein?

Answer 22

• n-terminus (actin binding domain)
• long spectrin like repeat domain: cytoskeletal portion of the dystrophin protein
• cysteine rich and C-terminus domains

Question 23

What is the clinical presentation of DMD?

Answer 23

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

Question 24

What is pseduohypertrophy?

Answer 24

replacement of muscle with adipose and fibrous connective tissue- enlarged calves

Question 25

What is lordosis?

Answer 25

excessive inward curvature

Question 26

what is kyphosis?

Answer 26

upward back curvature outward

Question 27

Describe Becker muscular dystrophy (BMD)

Answer 27

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

Question 28

DMD lacks what protein? What is the difference in this vs BMD?

Answer 28

DMD lacks dystrophin protein | BMD has some dystrophin protein but abnormal quantity and size

Question 29

What is the function of mitochondria?

Answer 29

provide cellular energy in the form of ATP for the cell

Question 30

What is mitochondrial myopathy?

Answer 30

muscle disease caused by mitochondrial dysfunctions

Question 31

Are mitochondria maternally or paternally inherited?

Answer 31

maternally

Question 32

What is heteroplasmy?

Answer 32

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

Question 33

What tissues are affected by mitochondrial disease?

Answer 33

brain/CNS, heart, skeletal muscles

Question 34

Describe MERRF

Answer 34

-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

Question 35

What are the main mutations of the tRNAlys in MERRF?

Answer 35

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

Question 36

Describe MELAS

Answer 36

-seizures -blindness - headaches -anorexia - recurrent vomiting - lactic acidosis - ragged red fibers age of onset : 2-10 years

Question 37

Describe Kearnes-Sayre Syndrome (KSS)

Answer 37

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

Question 38

describe CPEO

Answer 38

mild to moderate mt myopathy- mtDNA rearrangments | ptosis

Question 39

describe LHON

Answer 39

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

Question 40

What are the functions of erythrocytes?

Answer 40

transport oxygen forms the lungs to the tissues

Question 41

hemoglobin occupies ____ percent of the volume of erythrocytes and _____ percent of the cells dry weight

Answer 41

33, 90

Question 42

what is tissue switching?

Answer 42

switch phenomenon as to where red blood cells are made during development (around birth)

Question 43

What is the structure of hemoglobin?

Answer 43

2 alpha globin chains, 2 beta globin chains one heme per subunit that has iron that carries O2 four protoporphyrin IX rings

Question 44

What are the three types of hemoglobin in humans?

Answer 44

embryonic, fetal and adult

Question 45

What are the four types of globin chain in adult hemoglobin?

Answer 45

alpha, beta, delta, gamma

Question 46

What is the predominant form of hemoglobin in adults?

Answer 46

HbA which has 2 alpha and 2 beta subunits

Question 47

What are the alpha like chains of hemoglobin?

Answer 47

zeta embryonic and alpha

Question 48

What are the beta like chains of hemoglobin?

Answer 48

epsilon embryonic, gamma fetal, delta, beta

Question 49

How does HbS (sickle cell anemia) occur?

Answer 49

aa switch in position 6 in Beta globin of valine for glutamic acid

Question 50

Why does O2 flow from mother to fetus?

Answer 50

HbF does not bind well to 2,3 BPG and therefore has higher affinity for O2