Biochemistry - Muscles, Collagen, Rhabdo, Proteo

Question 1

What does creatine phosphate do for us in the body?

Answer 1

It buffers our ATP supply by giving ATP another phosphate when it uses one. It transfers a phosphate to ADP.

Question 2

What is CK-MM?

Answer 2

CK-MM is the muscle specific Creatine kinase

Question 3

What does the liver do with protein and creatine phosphate?

Answer 3

Turns it into urea. The kidney then excretes it.

Question 4

What promotes muscle building and protein intake hormone-wise?

Answer 4

Insulin

Question 5

What are the 4 essential amino acids for building muscle?

Answer 5

1. Selenocysteine 2. Leucine 3. L-Arginine 4. Beta-Alanine

Question 6

Why is Leucine so important? What about L-Arginine?

Answer 6

B-hydroxy-B-methylbutarate is a metabolite of the ketoacid formed from Leucine. L-Citrilline is the metabolite of the keto acid from L-Arginine and is important as a cofactor for NOS. L-Arginine also creates Creatine from its ketoacid.

Question 7

What does AMPK do? What inhibits it?

Answer 7

AMP Activated Protein Kinase A creates ATP and AMP. During recovery, AMPK is reduced.

Question 8

When do we get muscle fatigue?

Answer 8

When the recovery time between twitches is not long enough

Question 9

What are our short term muscle tibers? Long term? Red vs. white? What cellular processes do each of these fibers undergo for energy? Provide an example for each.

Answer 9

White = short term = Type II muscle fibers = anaerobic respiration. Like muscles in your hand for shaking hands (quick action) Red = long term = Type I muscle fibers = aerobic respiration (lots of m1tochondr1a!). Like muscls in your back for standing (long time)

Question 10

What is fatigue biochemically, particularly for type II fast twitch muscles?

Answer 10

Creatine phosphate is used in bursts (twitches) and then recovers between them. If you keep firing a fast twitch muscle without giving CP enough time to recover, you get fatigue.

Question 11

What is GLUT4?

Answer 11

Transporter that increases glucose uptake

Question 12

For energy measurements, what is MET? What is it equal to? What are the MET levels and their associated MET counts?

Answer 12

1 MET (Metabolic Equivalent) = 3.5 mL O2/kg/min < 6 MET = moderate > 6 MET = Vigorous > 10 MET = Intense

Question 13

What is the fick equation and what does it tell us?

Answer 13

where CO = Cardiac Output, Ca = Oxygen concentration of arterial blood and Cv = Oxygen concentration of mixed venous blood.

Also can be written as

VO2 = CO*(A-VO2) This second term means the difference in oxygen saturation between the arteries and veins.

Another important one to know here is CO = HR * SV (Stroke volume = End Diastolic Volume - End Systolic Volume)

Question 14

What is RER? What RER values do we get for different metabolisms?

Answer 14

The ratio between the amount of CO2 produced and O2 consumed in one breath (determined from comparing exhaled gasses to room air) is the respiratory exchange ratio (RER).

0.7 RER = FA oxidation

1 RER = Carbohydrate metabolism

Question 15

What is our max heart rate?

Answer 15

220 - age

Question 16

What is rhabdomyolysis? What is our main tool to diagnose it?

Answer 16

Type II muscle lysis due to stresses.

[CK] = elevated (usually 5x or more)

[CK] > 100,000 U/L is definitive

Sometimes less due to naturally elevation in African-Americans, marathoners, etc.

Question 17

Besides elevated CK, what other diagnostic tools do we have to test for rhabdomyolysis?

Answer 17

(+) Triad = Dark urine (myoglobinuria), muscle pain, weakness

(+) Muscle biopsy

(+) Caffeine Halothane contracture

(-) EMG/Nerve conduction

Question 18

There are some abnormal enzyme mutations that can lead to rhabdomyolysis. What are they?

What genes markers are associated with rhabdo?

Answer 18

Enzymes

Myoadenylate deaminase (AMPD1)

Myophosphorylase (PYGM)

Carnitine Palmitoyl Transferase (CPT2)

Genes

CKMM

ACTN3

MYLK (highest odds)

Question 19

What provides collagen its strength? How does collagen differ based on basement membrane vs. in the epithelium or connective tissue?

Answer 19

Coupled with laminin (basement membrane)

Coupled with elastin (epithelial/connective tissues)

rod-like, low solubility, structural strength due to carbohydrates, triple helix

Question 20

What is the genetic sequence for collagen?

Answer 20

Gly-X-Y repeats (42 exons)

Y = hydrated residue (mostly Pro + Lys)

Question 21

What are the four collagen types and their associated chains?

Answer 21

Type I - a2b

Type II - c3

Type III - d3

Type IV - e3

Question 22

How much carbohydrate is in Type I collagen and where do we find it?

What genetic abnormality do we see with it?

Answer 22

Type I: a2b, accounts for 90% of the total body collagen and occurs in the skin, bone, tendons, cornea, soft tissues, and scars. Has the least amount of carbohydrate.

Genetic defects cause Osteogenesis Imperfecta

Type ONE is found in bONE

Question 23

How much carbohydrate is in Type II collagen and where do we find it?

Answer 23

Type II: c3, occurs in cartilage (made by chondrocytes) and vitreous humor [major type of cartilage ~10% carbohydrate]

Homotrimer; Type TWO is the major type found in carTWOlage (cartilage), but is also found in skin and tendon

Question 24

How much carbohydrate is in Type III collagen and where do we find it?

What genetic abnormality do we see with it?

Answer 24

Type III: d3, aka “reticulin”, occurs mainly in blood vessel walls, other hollow organs, and fetal skin. It contains disulfide bridges between chains whereas type I and II do not. Found in scars and all adult soft tissues, but not in bone or tendons.

Defects lead to ehlers-danlos type 4 disease:

Aortic rupture

GI tract

Pregnancy problems

Skin fragility

Poor wound healing

Surgical problems

Question 25

How much carbohydrate is in Type IV collagen and where do we find it?

What genetic abnormality do we see with it?

Answer 25

Type IV: NON-FIBRILLAR, e3, is the collagen of basement membranes (mesh-forming; creates hexagonal lattices). Has disulfide bridges and has the highest carbohydrate content.

Structure allows for interruptions of the triple helix (due to high carbohydrate content)

Type FOUR is found under the floor (basement membrane, rhyme sound)

defects result in Alport syndrome

when targeted by autoantibodies, Goodpasture syndrome results

Question 26

What types of Osteogenesis imperfcta are there and what symptoms do we see?

Answer 26

Deficiency = Osteogenesis imperfecta (OI)

Autosomal dominant

Bone fragility hearing loss, blue sclera

Type 1 OI = mild, normal lifespan, fractures early in life

Mistaken for child abuse

Type 2 OI = perinatal lethal, absent mineralization

Exon mutation = Gly point mutations

Question 27

Describe the structure of collagen.

Answer 27

Left-handed peptides → Right handed triple helix

Central core = glycine (due to size)

Backbone = hydroxylated Y residue (hydrophilic)

Deficiency of hydroxyproline = melt temp below body temp

Question 28

Describe the domains of procollagen and what occurs to synthesize mature collagen fibers.

Answer 28

1. Ribosomes kick out a pro-alpha-chain, which is then hydroxylated at selected prolines and lysines
2. These hydroxylysines are then glycosylated
3. 3 chains come together to make a triple helix, and a procollagen molecule is secreted out of the cell with three domains: 1. Globular (N and C terminal) 2. Triple helical 3. Non-triple helical
4. Aminoprocollagen peptidase cleaves the N terminal off and carboxylprocollagen peptidase cleaves off the C-terminal. This gives us Tropocollagen which is asembled into the collagen fibril.

Question 29

What part of the collagen synthesis pathway does Ehlers Danlos affect?

Answer 29

1. The peptidase cleavage - This is ED7 where you get hypermobile joints
2. Cross linking of Tropocollagen to make fibrils - This is ED6 where you get hyperextended skin due t defects in lysyl oxidase and prolyl oxidase

Question 30

What is Menke’s Disease? Symptoms?

Answer 30

A type of CT disease caused by impaired copper absorption and transport

Leads to DECREASED lysyl oxidase activity (requires Cu2+ as a cofactor)

Due to the inability to tie the loose ends of collagen molecules, brittle, “”kinky” hair is seen, along with growth retardation and hypotonia

Question 31

What is scurvy?

Answer 31

Defect in Vitamin C (ascorbate) that affects the hydroxylation stage of collagen synthesis.

Question 32

How does collagen breakdown and how/why can tumors be involved?

Answer 32

Degradation - Normal remodeling by Zinc proteases

Can be induced by Tumor metastases, since certain collagens degrade endostatins produced by tumors (less angiogenesis)

Question 33

Difference between alpha and B proteoglycans

Answer 33

alpha is for energy

beta is structural

Question 34

What is the structure of proteoglycan?

Answer 34

Uronic acid and a dissaccharide (-osamine)

Question 35

What is the order of enzymes used to breakdown collagen and what diseases are associated with them?

Answer 35

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Iduronate sulfase – Hunter

a-L-iduronidase – Hurler (L-Idu accumulates)

NAG Sulfase – Maroteaux-Lamy

β -Hexase – Sandhoff

β -Glucase – Sly syndrome (MPS7)