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Question 1

What are Secondary active co-transporters.

Answer 1

Two types:

• Symporter –> meaning the items are being transported together in the same direction. e.g. 1 glucose is pushed into the cell by using the concentration gradient of 2 Na. Note: Gatorade: rehydration is achieved with salt and glucose.
• Antiporter –>The ions go in opposite direction. Na is going down it’s concentration gradient from his to low and the Ca2+ goes in the opposite direction.

Question 2

What is the cause of an action potential?

Answer 2

The opening of Na+ channels leading to increases in the membrane potential.

Question 3

What is the resting membrane potential of a cell? To what level does it need to be depolarized for the runaway AP process to take place?

Answer 3

~ -65mV is the membrane potential. (Note some textbook values go as high as 72mV) -a Cell is typically depolarized by reaching the ~ -50mV mark at which point the runaway AP effect occurs.

Question 4

Describe the characteristics of Na+ channels.

Answer 4

-They are voltage gated. There are two kinds of voltage-sensitive gates. 1. Activation gate –>these open as the cell depolarizes. 2. inactivation gate –> open when the cell is at rest. they swing shut as the cell depolarizes. Note: the inactivation gate open/close slower than activation gates.

Question 5

Describe the characteristics of K+ channels.

Answer 5

-These are voltage-gated and resets the membrane potential after the AP is triggered. -Maintains a high [K+] inside the cell. -Opening the K+ selective ion channels then leads to K+ Exiting the cell down its concentration gradient and pushing Vm back down to its resting value. -

Question 6

Describe which channels/gates are open during the absolute and relative refractory period?

Answer 6

°Absolute Refractory Period–> The activation gate of Na+ channel is open but the inactivation channel has closed. During this time, the K+ ion channel is open and K+ is flowing out of the cell. No new AP is possible during this time. °Relative Refractory Period –> both gates of the Na+channel have closed but the K+ ion channel is still open. New AP are possible but still unlikely.

Question 7

When do partial Action potentials happen?

Answer 7

They don’t! AP’s are all or none!.

Question 8

How is the positive feedback leading to opening of more and more Na+ ion channels stopped?

Answer 8

The closing of the Na+ ion channel “inactivation gate” ends the positive feedback and marks the beginning of the absolute refractory period.

Question 9

What allows for the high firing rates of action potentials?

What is the factor of safety?

Answer 9

• High rates of action potential generation also requires “more-than-minimum” number of Na+ channels. This is especially true when we consider that axons branch so the active locus has to depollarize both branches. The extra number of Na+ channels allows the additional action potentials to be fired-off before all the Na+channel “inactivation gates” have reopened.
• Axons have 5-10 times more na+ channels than the minimum needed for an AP. The factor of safety is 5-10x.

Question 10

What is the benefit of the mechanism of action potentials for long -range signaling?

Answer 10

With the mechanism of action potentials, the voltage signal is regenrated at several points a long the axon so that it doen’t degrad with distance. This is done by the voltage-gated channels. Without these channels, the signal would decay over a short distance and the neurons could not communicate over long distances.

Note: This is how novocaine works, which blocks the voltage-gated Na+ channels resulting in degradation of the signal.

Question 11

What is the practical importance of the neuron length constant?

Answer 11

• The length constant is the distance you need to travel away from the source before the voltage goes down by a factor 1/e ( this is roughly 1/3). i.e. rouhgly 2.5 mm.
• Clinical practice: using novovaine to block AP propagation along a segment of pain fibers–> we would need to depolarize at the end of the anesthetized region to be below AP threshold: a few times the length contatn ( a few mm) suffices.

Question 12

Discuss the factors that increased the action potential propagation?

Answer 12

• Bigger length constant–> longer range signalling in the sam eamount of time leads to an increase of speed.
• Fatter axons –> enables faster signalling
• Increasing membrane resistance–> increases the speed. Think “insulation” such as from the myelin sheaths.

Question 13

Can action potentials travel in both directions?

Answer 13

Sort of…

• If an action potential is triggered in a neuron at rest and in the middle of its axon (half way between the soma and dendrite).. yes the signal will travel to the soma and the dendrites.
• In the standard case though, the action potential will not move backwards towards its point of origin (normally the soma) because of the refractory period. Thus the AP wil only move “forward”.

Question 14

Discuss the effects of axon resistance (Ra) and membrane resisitance (Rm).

Answer 14

• Ra is like the resistance along the length of a wire.
• Rm is like the resistnace from insulation (e.g. myelin)
• Axons with low Ra and high Rm will have long length constants and thus fast propagation velocities.

Question 15

Describe the function/Location of Shwann cells and oligodendrocytes.

Answer 15

• These two types of cells wrap around axons and insulate them in a myelin sheath.
• Schwann cells in the PNS.
• oligodendrocytes in the CNS.

Question 16

Discuss the role and strucure of Myelin on axons and the propagation of AP.

Name one disease assocaited with damage of Myelin sheaths .

Answer 16

• Myelin speeds up long-range signaling. This is especially true for thin axons which otherwise will have more over all resistance to AP propagation.
• There are intermittent gaps in the myelin covering of the axons. These gaps are called “Nodes of Ranvier”. Voltage-gated ion channels regenerate the AP at this nodes.
• Multiple sclerosis leads to damage of muyelin sheaths impairing communication betwen differnet parts of nervous sytem–> impaired motor control, etc.

Question 17

What is the function of action potentials?

-What are factors to consider so that the action potential is propagated the full length of the neuron?

Answer 17

• To carry out long range signaling wihtihnt he nervous system.
• There must be enough current along the axon so that the neighboring segment depolarizes to the AP threshold and triggers an AP in that segment.

Question 19

Zellweger spectrum disorders:

Mutation

Symptoms

Biochemical Diagnosis

MRI findings.

Answer 19

-Mutation of PEX (~13 genes) inhibits the formation of peroxisomes.

• Symptoms: –> Severe hypotonia, floppy baby, large anterior fontanelle, characteristic facial features, Hepatosplenomegaly, seizures adn global delay.
• Biochemical Diagnosis: Elevated VLCFA, BCFA

-MRI: Severe leukodystrophy

Question 20

Rhizomelic Chondrodysplasia Punctata Type 1

Answer 20

Mutated PEX7 gene.

Symptoms: Short long-bones (Rhizomelia), Epiphyseal stippling (chondrodysplasia seen as speckled bone pockets). Facial dysmorphisms, cataracts (starting at birth), intellectual disability. Symptoms are variable in severity with milder forms known.

Biochemical Dx: Low Plasmalogens, BCFA elevated, VLCFA normal.

Prognosis: 99% of children don’t make it past the 2nd year.

Question 21

X-linked Adrenoleukodystrophy

Answer 21

• This is the most common peroxisomal disorder resulting from mutated ABCD1 gene.
• This is the only peroxisomal disorder on the new born screenign test.
• Biochemical Dx–> Elevated straight VLCFA (C24-C26) in blood.
• Pathophysioloy–> Accumulation of saturated (C24 and C26) CLCFA and destruction of myelin sheaths/adrenal cortex.

X-linked: 80% of female carriers have elevated VLCFA. (100% males from birth).

Question 22

Desribe general characteristics of peroxisomes.

Answer 22

• Dysfucntion of a single gene or abnormal biogenesis occurs from monogenic autosmal recessive or X-linked diseses.
• bud from the ER.
• Prepares cargos for: De novo lipogenesis, VLCFA & BCFA catabolism, Bile acid synthesis, DHA synthesis (brain and retina). Extinguishes ROS, RNS adn H2O2.
• Shares many functions with mitochondria.
• Cuts fatty acids that are ~20+ carbons in length, down to 18 Carbon fatty acids so that mitochondria can cleave this for energy via Beta-oxidation.

Question 23

What are inbron erros of metablism? give an example.

Answer 23

“Inborn Error” –> genetic heritability, single gene, usually autosomal recessive, consanguinity effects.

“of Metabolism” –> energy, waste, storage, synthesis, transport.

-E.g. Phenylketonuria. Presymptomatic discovery of this condition in newborns leads to excellent outcome.

Question 24

Describe some general characteristics of Peroxisomal disorders.

Answer 24

Defects in peroxisomes cause sytem wide problems:

CNS: Hypotonia, seizures, spasticity, leukodystrophy, behavioral changes, encephalopathy, hearing loss.

PNS: sensorimotor polyneuropathy

Ophto: Cataracts, retinopathy, glacucoma, vision loss.

ENT: Craniofacial dysmorphisms.

GI: Liver dysfunction, cholestatis, hepatomegaly.

Endo: Adrenal insufficiency/Addison’s, hypothyroid, hypogonadism.

Skeletal: Bony stiplling, limb malformations, scoliosis, short stature, delayed tooth eruption.

Renal: Cysts, renal insufficiency.

Skin: Ichthyosis.

Question 25

What are the 2 classifications of Peroxisomal Disease?

Answer 25

1. Peroxisomal Biogenesis Defects: –> Organnell totally dysfunctional
2. Single functional gene disorders: –> 10 individual disorders and phenotypic spectrusm.
   - Combined prevalance of these is 1/5,000.

Question 26

Clinical findings of X-linked Adrenoleukodystrophy

Answer 26

1. Childhood Cerebral (males only, 35 % of affected). Rapid progression ( 2 years is average from onset to death)—Addisons (adrenal Failure) onset at any age, psychomotor deterioration -4-12 yo— Behavioral changes (aggresion, ADHD) and changes in handwriting (Fine motor— Vison and hearing loss, loss of motor function.
2. Adrenomyeloneuropathy( AMN 40-45% of affected). late 20’s in males leading to progressive paralysis and sphincter and sexual dysfunction. 20 % of female carriers will experiene a Milder presenation.
3. Addison disease ony (10% of affected).

Question 27

Surveillance and Tx of X-ALD

Answer 27

Lorenzo’s Oil:substreate replaement therapy –> Large trials have not shown great benefit; still ongoing.

Treatment: BMT–> Is initiated when MRI changes but before clinically symptomatic: timing is crucial. This cannot reverse symptoms. Succes of BMT is excellent with ~80% having a 5 year survival.

-New born screenign for X-ALD is beginning.

Question 28

The osmolarity, or osmotic concentration (osmolar, osM; milliosmolar, mosM) is summed by…?

Answer 28

It is the summed concentration in formula weights of all solute particles – undissociated molecules, anions and cations.

e. g.
a. 100 mM NaCL –> 200 mM
b. 100 mM Glucose + 100 mM NaCl–> 300 mM

Question 29

How do you convert from mM to mEq?

Answer 29

This is a two step process:

1. for each ion, covert to mosM
2. multiple by valance of the ion in question.
   e. g. 100 mM K2SO4: K+ =__mEq SO42- =__mEq
3. 200 & 100 respectively
4. multiply by their valence so 200x1 and 100x2

= 200mEq for K+, and 200 mEq for SO42-

Question 30

DM1 General knowledge

Answer 30

1.25M pepoe have T1D.

40K dx each year.

less than 1/3 of people achieve target bg contorl levels.

T1D is associated twith an estimated loss of life of 13 years.

Incidence is rising 3-5% per year.

Question 31

Name the 3 vesicular coats and their function.

Answer 31

1. Clathrin–> involved in endocytosis. From the Plasma membrane to the golgi.
2. COPI –> involved in movement of vesicles between the ER and Golgi. COPI forms the vesicle in the Golgi and moves to the ER.
3. COPII–> Involved in movement of vesicles between the ER and Golgi. COPII forms the vesicle in the ER and moves to the golgi.

Question 32

Discussed the Clathrin mechanism.

Answer 32

Clathirin binds to “Adaptin” which in turn binds to a membrane protein. The clathrin and adaptin molecules will disocciate once the vesicle has been pinched off.

-The vesicle can’t fuse with any other membranes until the vesicular coat protein (Clathrin) and it’s associated proteins dissociate from the newly formed vesicle.

Question 33

pH of the ER lumen and pH affects on vesicle memnrame/trasport/enzymes.

Answer 33

The lumen of the ER is pretty close to neutral. as we move toward the golgi, the lumen becomes more and more aciidic. Binding and unbinding is pH dependant. Don’t forget enzymes are affected by the pH.

E.g. In acidic enviorment KDEL peptide will bind to the receopt for …COP1.

Question 34

Importance of Protein retrieval: Osteogenesis Imperfecta I

Answer 34

Several genes are reponsible for OI, the KDEL gene is one of them and codes for an enzyme that posttranlationally modifies collagen. This protein functinos fine, but it is not being transported back to the ER to be reused.

Question 35

Types adn mechanism of chaperone proteins

Answer 35

Two major types of chaperone proteins

1. hsp70 family –> help fold protein by binding to exposed hydrophobic patches in incompletely folded proteins.
2. hsp 60 family –> Forms large barrel-shaped structures to act as an “isolation chamber” into which misfolded proteins are fed to prevent their aggregation and help it to refold.