Biochem Ischemic Markers-Kandpal

Question 1

What is produced in glycolysis? Is this aerobic or anaerobic?

Answer 1

2 ATP and 2 NADH

anaerobic!

Question 2

What is the precursor for aerobic metabolism? What 2 things inhibit the production of this precursor?

Answer 2

acetyl CoA

Acetyl CoA and NADH inhibit pyruvate dehydrogenase (which converts pyruvate into Acetyl CoA)

Question 3

How much energy is produced from each Acetyl CoA?

Answer 3

3 NADH
FADH2
GTP

–> 12 ATP /acetyl CoA oxidized

Question 4

What is necessary for glycolysis to occur?

Answer 4

NAD+

necessary for aerobic metabolism

Question 5

What are fatty acids used for?

Answer 5

ENERGY –> produce much more energy than glucose

Fatty acids are metabolized by beta oxidation to produce acetyl CoA.

Acetyl CoA enters TCA cycle to generate NADH, FADH2 and GTP.

NADH and FADH2 are oxidized by ETC to generate ATP.

Question 6

Where does the heart get most of its ATP?

Answer 6

> 90% from mitochondrial oxidative respiration

heart cells are rich in mitochondria

Question 7

What organs can create creatine kinase?

Answer 7

kidney and liver

ATP synthesis from creatine kinase is 10x faster than from oxidative phosphorylation

Question 8

What enzymes and products are important in the creatine kinase system?

Answer 8

Enzyme(s):
Mitochondrial creatine kinase
Myofibrillar creatine kinase (regenerate ATP in myofibrils)

Product(s):

• Phosphocreatine in mitochondria
• ->Smaller than ATP (readily diffuses out)
• Creatine in cytoplasm
• ->Diffuses back into mitochondria

Question 9

What are the 3 forms of creatine kinase?

Answer 9

CK-MM
Skeletal and cardiac muscle

CK-BB
Smooth muscle and non-muscle cells

CK-MB
Cardiac muscle

Question 10

How does PPAR alpha respond to fatty acids? What will happen to PPARalpha levels in a pt with heart failure?

Answer 10

fatty acids up regulate PPARalpha and the enzymes in FA oxidation

heart failure–> less FA used –> decrease PPAR alpha

Question 11

What are the functions of the components of troponin?

Answer 11

T- tropomyosin binding
I- inhibitory function
C-calcium binding

Question 12

Relaxation of actin-myosin complexes depends on what?

Answer 12

ATP

depletion of ATP==> rigor

Question 13

What is associated with heart failure?

What are 2 classes of drugs used to treat heart failure and what is the energetic basis of these?

Answer 13

-decrease in ETC and ATP synthase activity
-increase in levels of uncoupling proteins
==> BOTH needed in ATP synthesis

• beta blockers==> improve phosphocreatine stores –> increase intracellular ATP transfer
• ACE inhibitors: reverse the reduction in ATP, creatine phosphate, creatine and the mitochondrial O2 consumption rate

Question 14

What causes decreased contractile function in heart failure?

Answer 14

decrease ATP transfer

Decreased levels of phosphocreatine and creatine
Decreased levels of mitochondrial CK and myofibrillar CK

Question 15

How does the amount of fatty acid oxidation in a heart failure heart compare to a normal heart? what will happen to glucose utilization in early heart failure?

Answer 15

advanced heart failure==> significantly decreased FA oxidation

glucose utilization will increase in early heart failure (because can’t use FA)

Question 16

What metabolic changes take place in myocardial infarction?

Answer 16

impaired blood supply–> decrease in oxidative phosphorylation and FA oxidation

-increase in glycolysis and depletion of glycogen

hypoxia compromises ETC —> NADH accumulation and less FA oxidation

Question 17

What will result from reperfusion of ischemic heart?

Answer 17

rapid FA oxidation and accumulation of acetyl CoA and NADH==> increase protons

also acetyl CoA accumulation inhibits pyruvate dehydrogenase –> lactate formation ==>

increase acidity!!

==> disruption of ion gradients==> ATP is used to fix the ion gradient and leaves insufficient ATP for cardiac mm.

Question 18

What should be given when ischemic heart mm is reperfused? Why?

Answer 18

FA oxidation inhibitors

to shift metabolism from GA to glucose oxidation (decrease Acetyl CoA)–> decrease lactate build up in the damaged heart mm.

Question 19

What takes place during the process of necrosis?

Answer 19

blood supply is compromised==> tissue and cell death==> cells swell and leak their content –> inflammatory response

will get elevated levels of enzymes due to tissue damage

Question 20

When will CK-MB levels be elevated after an incident of chest pain? for how long?

Answer 20

rise 4-8 hours after CP and will peak at 24 hours and return to normal at 48-72 hours

Question 21

How long will troponin levels remain elevated after an episode of chest pain?

Answer 21

remain elevated 3-10 days

will rise 4-6 hours and peak at 8-28 hours

Question 22

What is CRP a good marker for?

Answer 22

prognosis of atherosclerosis

helps to determine inflammation (which may be an indicator of atherosclerosis)

Question 23

Why is BNP a better marker for heart failure than ANP?

Answer 23

ANP is much higher in normal people.

in heart failure, BNP will exceed ANP

BNP has a wider range than ANP

Question 24

What is carnitine important in?

Answer 24

transport of FA

deficiency can lead to cardiomyopathy