Dom Biochem Flashcards Exam 1

Question 1

The immediate source of energy for muscle contraction is? Which enzyme is involved?

Answer 1

ATP—–>ADP + PiMyosin ATPase

Question 2

What does creatine kinase (CK) have to do with muscle contractions?

Answer 2

Transformation form ATP + Creatine to Phosphocreatine + ADP, and vice versa

Question 3

What does adenylate kinase (AK) have to do with muscle contractions?

Answer 3

Helps with transforming from 2ADP to ATP +AMP and backwards

Question 4

What are the energy sources for smooth muscle? major and secondary

Answer 4

Most from glycolysisCan also use lactate

Question 5

What is the preferred energy substrate used by cardiac muscles? Which others can be used?

Answer 5

Metabolism is almost totally aerobicPreferred: Fatty AcidsOthers: Glucose, Ketone Bodies, Lactate

Question 6

In the replenishment of ATP following muscle contractions, which enzyme is activated by AMP?

Answer 6

Glycogen phosphorylase B - glycogenolysis initiated

Question 7

In the replenishment of ATP following muscle contractions, which enzyme is activated by AMP, Pi, and NH3?

Answer 7

Phosphofructokinase-1 - glycolysis initiated

Question 8

In the replenishment of ATP following muscle contractions, which enzyme is activated by ADP?

Answer 8

Isocitrate Dehydrogenase - TCA cycle initiated

Question 9

In the replenishment of ATP following muscle contractions, which enzyme is activated by Ca++ ions? (4)

Answer 9

Glygogen phosphorylase (glycogenolysis active)Pyruvate dehydrogenase (glycolysis/TCA active)Isocitrate dehydrogenase (TCA active)Oxoglutarate dehydrogenase (TCA active)

Question 10

Describe McArdle’s Disease

Answer 10

A type V glycogen storage diseaseDeficiency in muscle glycogen phosphorylaseMyopathy due to defective glycogen breakdownPainful cramps and fatigue with exerciseno lactate increase during exercise (abnormal)**PRIOR ingestion of sucrose is beneficial

Question 11

What enzyme releases fatty acids from chylomicrons and VLDL?

Answer 11

Lipoprotein lipase

Question 12

Why are serum fatty acid levels decreased following increased blood glucose levels?

Answer 12

Insulin is secreted in raised blood glucose - insulin inhibits lipase responsible for releasing fats

Question 13

By what mechanism is most energy produced in Type I and IIa fibers?

Answer 13

oxidative metabolism

Question 14

By what mechanism is most energy produced in Type IIb fibers?

Answer 14

WHITE FIBERSglycogen mobilized for rapid release of substratelactate via ANEROBIC GLYCOLYSIS

Question 15

What is the major disadvantage of carbohydrate metabolism?

Answer 15

It is stored as hydrated form, so it produces about 7 times less energy per gram

Question 16

What happens to the lactate produced by white (IIb) muscles metabolism?

Answer 16

It goes to the liver to be used in gluconeogenesis (CORI CYCLE)

Question 17

What is most likely the major contributor to muscle fatigue?

Answer 17

Increase in Pi

Question 18

What are the 2 big theories that try to explain muscle fatigue? Describe them..

Answer 18

Increase in Pi – self explanatory (major contributor)Fall in pH - inhibiting PFK-1 and SR release of Ca+

Question 19

What is the major pathway of glycogen replenishment?

Answer 19

INSULIN activates glycogen synthase (b form to a)G-6-P presence does the same thing

Question 20

What are free fatty acids bound to in serum?

Answer 20

Albumin?

Question 21

Red fibers have a higher level of two certain proteins than white? Which has to do with their preference for oxidative metabolism? What proteins are important?

Answer 21

Fatty Acid Binding Protein (FABP)Lipoprotein Lipase (LPL)

Question 22

How does increased fat (spare) glucose?

Answer 22

Increased free fatty acids (B-oxidation) inhibits PFK-1, so less breakdown of glucose… Refer back to picture slide..

Question 23

Describe how AMP stimulates the uptake of fatty acids into mitochondria

Answer 23

REVIEW PICTURE FOR ANSWER

Question 24

Recall what happens in starvation (4 Points)

Answer 24

1. Glucose is reserved for brain2. Muscle uses fatty acids and ketone bodies3. Muscles provide amino acid C-skeletons for liver to use in gluconeogenesis4. Amino acids largely released as alanine and glutamine

Question 25

Does glucagon activate glycogen phosphorylase in muscle?

Answer 25

NO, survival mechanism in early man. Need energy to kill stuff in a starvation situation. So glycogen is saved for movement

Question 26

Major muscle fuel after 4h starvation?

Answer 26

Fatty acids

Question 27

Major muscle fuel after 1-2 days?

Answer 27

Fatty acids + Ketone Bodies

Question 28

Major muscle fuel after 3 weeks?

Answer 28

Fatty acids

Question 29

What hormone stimulates the breakdown of muscle protein to provide C-atoms for liver gluconeogenesis during days 1-2 in starvation?

Answer 29

CortisolThis decreases after day 2 as ketone bodies take over as major fuel source

Question 30

Excess acetyl CoA is converted to _____ (3) by liver mitochondria?

Answer 30

AcetoacetateB-hydroxybutyrateAcetone

Question 31

How does the muscle utilize ketone bodies as a fuel?

Answer 31

Ketone bodies are converted back to 2 molecules of actetyl CoA….. Enzyme? REVIEW Figure near end of lecture

Question 32

Muscle breakdown in starvation yields mainly which 2 amino acids?What is the major site of metabolism?

Answer 32

1. Alanine and Glutamine2. Branched-chain amino acids

Question 33

What is the major pathway of catabolism for cardiac muscle in the fed state

Answer 33

Oxidative (95%), mostly fatty acids, some glucoseCan oxidize lactate under extreme circumstances

Question 34

Which glucose transporter is important for uptake of glucose into cardiac muscle (response to insulin)

Answer 34

GLUT-4Insulin also stimulates PFK-2 to produce F-2,6- bisphosphate

Question 35

What happens in cardiac muscle metabolism during ischemic conditions?

Answer 35

(eg. MI)ATP levels fall, AMP levels riseAnerobic glycolysis is stimulated to compensate for the loss of aerobic ATP production via 2 AMP-mediated mechanisms.

Question 36

What are the 2 AMP mediated mechanisms of energy production in ischemic cardiac muscle?

Answer 36

Note: goal of both is to activate PFK-11. AMP activates AMPK - AMP-activated protein kinase which phosphorylates PFK-2. PFK-2 increases production of fructose-2,6-bisphosphate —> activeates PFK-12. AMP activates PFK-1 directly (via allosteric binding)Review picture on slide

Question 37

What are the 2 important X-linked dystophies?

Answer 37

Duchenne (DMD)Becker (BMD)THE REST ARE AUTOSOMAL

Question 38

What population is Oculopharyngeal Muscular Dystrophy (OPMD) prevalent?

Answer 38

French-Canadians

Question 39

Describe the etiology of DMD

Answer 39

30% new mutations Dystrophin gene virtually absentCause by frameshift mutations (e.g - deletion/duplication)

Question 40

Describe the etiology of BMD Becker

Answer 40

<2% new mutationsReduced or Modified Dystrophin geneCaused by point mutations(not frameshift like DMD)

Question 41

Where is the dystrophin gene located?What is it important for?

Answer 41

X chromasome (dont worry about detail)Codes for the dystrophin protein which is important for linking cytoskeletal proteins to transmembrane glycoproteins which connect to the ECM.

Question 42

What is used in the diagnosis and carrier detection for MD?

Answer 42

HIstory and Physical **SERUM CREATINE KINASEMuscle biopsyMultiplex PCRSCAIP (useful in prenatal diagnosis, internal primer sequencing)

Question 43

Describe the etiology of myotonic muscular dystrophy (MMD or DM - dystrophia myotonica)?

Answer 43

Autosomal dominant MOST COMMON MDAffects heart, smooth muscle, CNS, eye, and endocrine systemCaused by a repeat expansion*****Appears after adolescence, displays anticipation as well (more severe expression generation to generation)

Question 44

Symptoms of MMD?

Answer 44

MyotoniaMuscle WastingCataractsDiabetes MellitusFrontal BaldingMild Mental DeteriorationTesticular atrophy*reveiw pic of muscles generally affected (mostly extremities and neck +diaphragm)

Question 45

In MMD, what is the difference between DM1 and DM2?

Answer 45

DM1 - is more common (98%), shows anticipation, chromosome 19 (More details??)DM2 - unlikely, milder in presentation, chromosome 3, no anticipation?

Question 46

Onset/Death in DM1 classic case?

Answer 46

Onset: 10-30 yrsDeath: 48-55 yrs

Question 47

Onset/Death in DM1 congenital case?

Answer 47

Onset: birth - 10 yrsDeath: 0-45 yrsNote mild version shows up (20-70yrs) and can live (60yrs-normal)

Question 48

Mechanism of MMD diagnosis?

Answer 48

Targeted mutation analysis: PCR to find repeat sequence, Southern blot for larger expansions

Question 49

Describe Facioscapulohumeral Dystrophy (FSHD)

Answer 49

Autosomal dominantPrincipally affects upper body Defect in long arm of chromosome 4Onset usually 10-25 yrs old Non-symmetrical pattern of weakness, scapular winging, slight scoliosis

Question 50

Describe Limb-girdle Muscular Dystrophies (LGMD)

Answer 50

Autosomal dominant AND recessiveCaused by mutations in genes encoding sarcoglycans 4 most common formsCK levels normal to very high (in some recessive forms)

Question 51

Describe oculopharyngeal musculodystrophy (OPMD)

Answer 51

Autosomal dominantCaused by an expansion of GCN repeat within the gene encoding the poly(A) binding protein (PABPN1)Characteristic drooping eyelids, weakness in facial and pharyngeal muscles - can extend to limbsCK levels are usually normal or mildly elevated

Question 52

Describe Congenital Musculodystrophy (CMD)

Answer 52

Autosomal recessive, presenting soon after birthHypotonia followed by muscle weakness 50% *Due to a deficiency in laminin-2, while others due to defective glycosylation of alpha-dystroglycans (muscle fiber destruction due to impaired binding of laminin)CK levels usually moderately high

Question 53

Describe Bethlem Myopathy

Answer 53

Autosomal dominant, usually onset before 5Mutation affecting Collagen - VIProximal muscle weakness (mild to progressive)Lifespan not affected

Question 54

Malignant Hyperthermia (MH)

Answer 54

Feared (Rare) complication of general anesthesiaDMD, BMD, MMD patients may be particularly susceptiblePathologic release of Ca++ in response to anesthesiaHypermetabolic Sate

Question 55

What is the treatment for Malignant hyperthermia (MH)

Answer 55

dantrolene sodium