Biochemistry Review Q's Flashcards
1-32 = artherosclerosis 33-64= energy utilization
What are four things plaques are made up of?
cholesterol
lipids
inflammatory cells
Ca deposits
What occurs if the femoral artery gets occluded due to atherosclerosis?
intermittent claudication (condition in which cramping pain in the leg is induced by exercise)
What occurs if the internal carotid artery gets occluded due to atherosclerosis?
ischemia and cerebral infarction
What is the predominant cell in early atherosclerotic lesions?
macrophages
Where dos lipid accumulate in the arteries?
tunica intima
What are foam cells? Where can they be found?
Foam cells are a type of macrophage that localize to fatty deposits on blood vessel walls, where they ingest low-density lipoproteins and become laden with lipids, giving them a foamy appearance.
Where are smooth muscle cells located in the blood vessels?
in the tunica media
What occurs to the smooth muscle cells (SMC) of blood vessels during atherosclerosis?
foam cells release cytokines and growth factors that induce the SMCs to move to the tunica intima (they’re also changed to a repair phenotype instead of a contractile phenotype)
early atherosclerotic lesions are also called
fatty streaks/fatty dots (the first grossly visible lesion in the development of atherosclerosis)
Which lipoprotein reduces risk of atherosclerosis? Why?
LDL or HDL
HDL; it moves the lipids from the body back to the liver, this is why its called the good cholesterol.
LDL moves lipids to the body
What are the two ways cholesterol inflex is regulated?
too much free cholesterol inhibits the main cholesterol synthesis enzyme (HMG-CoA reductase) and it can also inhibit the DNA transcription of LDL receptors
What occurs to the cell if ACAT enzyme is defective?
the cell would get damaged. The ACAT enzyme acts to esterify and store free cholesterol, without it the free cholesterol would build up and cause damage to the cell (its toxic)
What are the receptors that uptake cholesterol via regulated versus unregulated pathway?
regulated= LDL receptors (they uptake native LDL)
unregulated= SR-A, CD36, oxLDL receptor (they uptake modified LDL’s!!)
What are the three uses for free cholesterol in the cell?
make steroids
make cell membrane
esterify and store it
Which of the following is a full transporter?
a. ABCA1: ATP-Binding Cassest Transporter A1
b. ABCG1: ATP-Binding Cassest Transporter G1
a. ABCA1: ATP-Binding Cassest Transporter A1
(ABCA1 gives both phospholipids and cholesterol esters to form the small HDL; ABCG1 only gives cholesterol esters to make the HDL bigger)
Where/Which receptor do the full HDL lipoproteins bind to?
the SR-B1 receptor in the liver
(it takes the lipids from the fat HDL and returns it to the circulation as a skinny legend)
How do modified LDL’s lead to inflammation?
by binding to toll like receptors (those activate inflammation)
(these modified/oxidized LDL’s get consumed by the macrophages by the unregulated scavenger receptors, but they also bind to the toll-like receptors on these macrophages and activate inflammation)
How does adaptive immunity play a role in atherosclerosis? explain.
dendritic cells (antigen-presenting) uptake the oxidized LDL, go to lymph, and present them to naive T cells. The naive T cells differentiate and go to the plaque to kill the oxidized LDL- this causes inflammation
What can be used biomarkers in coronary vascular disease?
inflammatory mediators
(use to diagnose)
What are the two hypotheses that explain how atherosclerosis develops?
1- response to injury (injury to endothelium caused the lipoproteins to go into the vessel wall and oxidize)
2- lipid retention (hyperlipidemia causes a the lipoproteins to go into the vessel wall and bind to matrix protein, aggregating and oxidizing) (…but why does it go into the vessel wall? because it’s going from the high lipid concentration in the blood to low lipid concentration on the vessel wall)
T/F: once the atherosclerotic plaque ruptures, occlusion is imminent
false, it doesn’t have to cause an occlusion, it can heal and cause stenosis instead
What can reduce the size of plaques?
efferocytosis (when dying cells are removed by phagocytic cells) or when cells migrate out of the plaque
Explain how plaques initiate
LDL accumulates in tunica intima and they get oxidized
oxidized LDL makes endothelial cells make adhesion receptors (ICAM, VCAM)
adhesion receptors attract monocytes and transform them into macrophages
macrophages express the scavenger receptors to uptake the oxidized LDL and transform to foam cells
What are four harmful effects of oxidized LDL?
- proliferation and migration of smooth muscle cells
- inducing endothelial cells to make adhesion molecules
- inducing MCP-1 (macrophage chemotactic factor protein-1) so monocytes get attracted to the site
- increase MCSF (macrophage colony-stimulating factor) so monocytes can differentiate into macrophages
Which cells mainly aid in producing the fibrous cap? how?
vascular smooth muscle cells; they are the ones that migrate into the tunica intima and produce extracellular matrix, collagen, elastin, etc. This forms the fibrous cap while the inner portion is filled with foam cells/macrophages.
Which plaque enzyme acts to degrade the fibrous cap?
metalloprotease
How does the necrotic/lipid core of the plaque form?
the macrophages that have lots of free cholesterol die first (they die because the free cholesterol is toxic), and release the free cholesterol into the plaque killing cells and forming the core (lipids and debris)
T/F: thrombosis symptoms appear as soon as the lipid core is formed
false; the lipid core doesn’t cause any symptoms when its under the fibrous cap, but when the plaque ruptures and the core interacts with the circulation, symptoms appear
T/F: apoptosis of macrophages is good for the atherosclerotic plaque development
false; apoptosis of macrophages can be both good and bad for the atherosclerotic plaque development. In the early lesion the apoptotic debris gets cleared, so it hinders plaque development. But later on when the plaque is bigger, the debris doesn’t get cleared, thus making the plaque bigger.
What plays a physical role in disrupting the continuity of the fibrous cap?
the free cholesterol makes sharp crystals that can mechanically/physically pierce the fibrous cap open
After a plaque ruptures and a thrombus is formed, what process can result in stenosis?
constrictive remodeling
What’s the difference between M1 and M2 macrophages?
M1= proinflammatory, initiate the plaque formation
M2= antiinflammatory, reduce plaque size and help tissue remodeling (matrix synthesis)
What precent of the bodies oxygen is used up by the heart?
10% of body oxygen consumption
Which of the following cardiac energy stores are short-term?
– phosphocreatine
– glycogen
– triacylglycerols
– phosphocreatine
keep the heart going for 5 to 10 sec.
Which becomes an important energy source in heart failure?
a–Glucose
b–Fatty acids
c– Lactate and Pyruvate
d– Amino acids
e– Ketone bodies
e– Ketone bodies
What are two heart functions that cause it to need high amounts of energy?
ions pumps
+
contractile apparatus
Which is insulin insensitive?
GLUT 1 or GLUT 4
GLUT 1
T/F: lactate is a waste product that’s produced when the heart uses glucose to make ATP
false, it’s not a waste product because the heart has O2 and can oxidize lactate to pyruvate, then make more ATP from it via to kerbs cycle
(its a waste product in muscle)
How does glucose enter cardiac cells?
via GLUT1/4 receptors
they go from high to low concentrations so no energy is needed
Low does lactate enter cardiac cells?
vis monocarboxylate transporters
What’s the main way of cardiac cells to make ATP?
oxidative phosphorylation
How can the heart utilize triacylglycerol?
via lipoprotein lipase activity (has high levels of this enzyme)
Which of the following needs oxygen to be able to be converted into ATP?
a. glucose
b. fatty acids
b. fatty acids
(A=produce some ATP without using O2)
On average, how does the heart produce most of the energy it uses (which method)? Where does it get the energy come from mostly?
90% of total myocardial energy produced by oxidative phosphorylation (mitochondria)
20% of energy from glucose and the remainder of energy from fatty acids
T/F: as a fetus develops, his heart relies less on fatty acids and more on glucose
false, the opposite is true. In fetal life the circulatory load is low and the heart uses glucose (limited oxygen availability), but then with development, the heart load increases and fatty acids are used for energy.
Explain what causes the heart to use more glucose as fuel when we’re fed.
higher insulin causes GLUT4 (glucose transporters) to bring more glucose into cardiac tissue
the insulin also decreases free fatty acid release from adipose tissue
the insulin also activates ↑ acetyl-CoA carboxylation and thus ↑ malonyl-CoA- this inhibits CPT-1 (which is used to transport fatty acids into the mitochondria for beta oxidization)
Explain how the heart uses more fatty acids for fuel when patient is exercising.
Exercise uses up ATP→AMP levels increase→that increases AMPK→AMPK inhibits acetyl-CoA carboxylase (which makes acetyl CoA into malonyl CoA)→malonyl CoA decreases (malonyl CoA inhibits CPT-1, which helps fatty acids get into mitochondria)→CPT-1 is more acitve→ more fatty acid beta-oxidation
T/F: CPT-1 in the heart is much more sensitive to inhibition by malonyl CoA than liver isoform
true
What two things activate VS what two things inhibit
Pyruvate dehydrogenase (PDH)
activate= Ca + Mg
inhibit= Acetyl-CoA + NADH
Pyruvate dehydrogenase (PDH) controls the hearts oxidization of two things.
oxidation of glucose and lactate by the TCA cycle in the myocardium
Which amino acid gives us pyruvate?
a. aspartate
b. glutamine
c. alanine
c. alanine
Which amino acid gives us fumarate?
a. aspartate
b. glutamine
c. alanine
a. aspartate
Which amino acid gives us alpha-ketoglutarate?
a. aspartate
b. glutamine
c. alanine
b. glutamine
(glutamine/ glutamate give us alpha ketoglutarate)
Which type of fuel does the heart work best while using?
the heart works best when using a mixture of metabolic fuels
Does oxidative phosphorylation need oxygen?
yes
(oxygen is the electron acceptor of complex IV of the electron transport chain…)
How does cardiac ischemia cause calcium overload?
when oxygen supply drops, we cannot use fatty acid oxidization for fuel, so we use glycolysis (which doesn’t use oxygen and doesn’t produce as much ATP)
Glycolysis produces NADH, which we then re-oxidize into NAD+ by making lactate. The problem starts when lactate (which is acidic) build-up and affects the ion pumps, which then lead to Ca overload.
The pumps that aid in Ca efflux (Na-Ca exchange) also don’t get enough energy to function, so that causes the Ca to stay in the cell and accumulate.
Explain reperfusion damage.
(ROS involvement)
oxygenated cardiac cells produce antioxidants to protect itself from the free radicals (which damage the cell membrane). But if a patient has an MI (example), the cardiac cells are unable to keep producing the antioxidants- which causes the free radicals (O2) to damage the cell membrane.
When reperfusion occurs and the cells get highly oxygenated blood, free radicals are formed (O2) and they end up damaging the cell membrane even more (no antioxidants to balance out the high oxygen-the antioxidants don’t have time ti be made)
T/F: during ischemia, the surrounding cardiac tissue uses fatty acid as fuel
true; Fatty acids dominate as a substrate for residual oxidative metabolism due to increased plasma levels of fatty acids
During reperfusion which acts as a fuel
a. fatty acid oxidation
b. glucose oxidation
a. fatty acid oxidation
The dominance of fatty acid oxidation during reperfusion inhibits glucose oxidation
in heart failure, which is the cardiac fuel source?
a. glycolysis
b. fatty acid oxidation
a. glycolysis
(due to decreased oxygen availability)
Describe the fetal heart metabolic profile.
high glycolytic capacity
low mitochondrial oxidation capacity
What two conditions copy the fetal heart’s metabolic profile.
cardiac hypertrophy and cardiac failure
(high glycolytic capacity+ low mitochondrial oxidation capacity)
How is shifting oxidative metabolism from fatty acids to glucose beneficial?
– Reduced oxygen requirements
– Reduced accumulation of fatty acids and toxic fatty acid metabolites (in a failing heart, the mitochondria is damaged and cannot oxidize FA, the FA intermediates build up. We switch to glucose use so we stop this build-up)
What lifestyle choices may help preserve the heart activity of patients with heart failure?
ketogenic diet
(heart then uses ketone oxidization for energy)
** not clear if this is beneficial yet- its in a tafreeg so just ignore this I guess
