Exam 3 Fatty Acid Beta Oxidation

Front 1

fatty acids are a major source of fuel in the body:
-supply ... needs between meals and during periods of exertion
-during overnight fasting, fatty acids become major fuel source for ... muscle, ... muscle, and ...
-one molecule of a FA yields (more or less) ATP than a molecule of glucose

Back 1

-energy
-cardiac
-skeletal
-liver
-more

Front 2

fatty acid storage in adipose cells occurs as what?

Back 2

triglycerides

Front 3

mobilizatoin of FAs from adipose:
-triglycerides in adipose tissue under go ... (breakdown of fats) into fatty acids. These fatty acids then travel through the blood to the muscle cell and undergo ... (process of buring fatty acids) into ... (main product of beta-oxidation)

Back 3

lipolysis
beta-oxidation
acetyl CoA

Front 4

the particles predominantly responsible for the transport of triglycerides (and FAs) in the blood are ... and ...

Back 4

chylomicrons
VLDL

Front 5

what releases free fatty acids from triglycerides?

Back 5

lipases

Front 6

free fatty acids travel in blood complexed with ... (most abundant protein in blood)

Back 6

albumin

Front 7

fasting leads to high ... levels (low ... levels) which signals cAMP levels to rise within adipocytes which leads to an activation of ..., which phosphorylates and activates hormone-sensitive lipase

Back 7

glucagon
insulin
protein kinase A

Front 8

cellular uptake of FAs:
-fatty acids enter cells through 2 routes:
-... through the plasma membrane
-transport by a ... (...) located on the plasma membrane
-an additional fatty acid binding protein may facilitate intracellular trasport of fatty acids, particularly transport to the mitochondria (where beta-oxidation occurs)

Back 8

diffusion
fatty acid binding protein
FaBP

Front 9

what happens to the free FAs once they enter cells:
-fatty acids ultimately oxidized to ... and ... to produce energy (...)
-acety CoA (the major precursor that enters into the TCA cycle) produced through beta-oxidation of FAs in the liver can be (a.) converted to ... (which can also be used for fuel) or (b.) enters the ...
-glycerol and energy derived from lipolysis is used by the liver for ...

Back 9

CO2
water
ATP
ketone bodies
TCA cycle
gluconeogenesis

Front 10

fatty acids must be activated in the cytoplasm before being oxidized in the mitochondria. Activation is catalyzed by ..., which is expressed on the outer mitochondrial membrane

Back 10

fatty acyl-CoA synthetase

Front 11

acyl CoA synthetase uses ... to form fatty acyl CoA thioester bonds

Back 11

ATP

Front 12

once fatty acyl-CoA is generated, it can be used by # multiple pathways in the cell

Back 12

3

Front 13

If it enters into the mitochondria, fatty acyl CoA is used to generate energy through ... or ...(formation of ketone bodies).

Back 13

beta-oxidation
ketogenesis

Front 14

if it enters into the ER or peroxisomes, fatty acyl-CoA can be used for membrane synthesis of ... and ...

Back 14

phospholipids
sphingolipids

Front 15

Finally, fatty acyl CoA can be reconverted back into ... in the ER

Back 15

triglycerides

Front 16

transport of FA into mitochondria requires the ... shuttle:
-... serves as the carrier/transporter of fatty acids across the inner mitochondrial membrane.
-obtained from the ... (mostly in red meats and dairy) or synthesized from ... in the liver
-synthesis requires ... and ...
-stored in skeletal muscle

Back 16

carnitine
carnitine
diet
lysine
vitamin C
S-adenosylmethionine (SAMe)

Front 17

carnitine palmitoyl transferase I (CPT I):
-aka carnitine acyltransferase (CAT I)
-found on the ... mitochondrial membrane
-rate-limiting enzyme (inhibited by malonyl CoA)
-transfers the fatty acyl group to carnitine, forming fatty acylcarnitine, which is then translocated into the mitochondrial ... by carnitine acylcarnitine translocase (shuttle)

Back 17

outer
matrix

Front 18

Carnitine palmitoyl transferase II (CPT II):
-aka carnitine acyltransferase II (CAT-II)
-located on the ... mitochondrial membrane
-transfers the fatty acyl group back to CoASH (re-forming the fatty acyl CoA) and releases the ... for recycling

Back 18

inner
carnitine

Front 19

what is this?
-the enzyme expressed on the outer mitochondrial membrane that transfers the fatty acyl group from fatty acyl-CoA to carnitine. The fatty acyl group must be attached to carnitine to be able to get into the mitochondria for beta-oxidation to occur. (in other words, the inner mitochondrial membrane is impermeable to fatty acyl CoA, much like it is impermeable to acetyl CoA).

Back 19

carnitine palmitoyl transferase I (CPT I)

Front 20

what serves as the carrier of the fatty acyl-CoA across the inner mitochondrial membrane?

Back 20

carnitine

Front 21

what is the enzyme expressed on the inner mitochondrial membrane that translocates the fatty-acyl-carnitine into the mitochondrial matrix?

Back 21

carnitine acylcarnitine translocase

Front 22

what is the enzyme expressed on the inner mitochondrial membrane that transfers the fatty acyl group back to CoA (reforms the fatty acyl CoA) and releases carnitine for recycling?

Back 22

carnitine palmitoyl transferase II (CPT II)

Front 23

what are these?
-inability to transport fatty acids into the mitochondria for oxidation
-occurs in newborns (particularly pre-term infants), patients undergoing hemodialysis, patients with organic acidemia
-symptoms: muscle weakness, muscle cramping, cardiomyopathy, hepatomegaly, encephalopathy, sudden death

Back 23

deficiencies in carnitine

Front 24

CPT I deficiency:
-autosomal ... defect in CPT I gene
-primarily affects ... in the liver
-symptoms usually present after a period of fasting or after a gastrointestinal illness: ...(low amounts of ketone bodies in blood stream) and hypoglycemia, lethargy, seizures, coma

Back 24

recessive
fatty acid oxidation
hypoketosis

Front 25

CPT II deficiency:
-autosomal ... defect in CPT II gene
-3 subtypes: ... CPT-II deficiency (most common), ... CPT-II deficiency (similar to CPT-I), and ... CPT-II deficiency (rare, fatal)
-symptoms of myopathic CPT-II deficiency: onset usually in adolescence or adulthood, recurrent muscle pain, fatigue, and myoglobinuria (particularly following exercise), often misdiagnosed (fibromyalgia, chronic fatigue)

Back 25

recessive
myopathic
hepatic
multiorgan

Front 26

the beta-oxidation spiral:
-fatty acyl group sequentially cleaved into 2-carbon ... units
-initial step is oxidation of the ...

Back 26

acetyl CoA
beta-carbon

Front 27

each oxidation at the beta-carbon of the fatty acid chain involves what 4 intermediate steps?

Back 27

oxidation
hydration
oxidation
cleavage

Front 28

what is the enzyme that catalyzes the first step (initial oxidation of the beta-carbon) in the spiral and is also involved in several metabolic disorders?

Back 28

acyl CoA dehydrogenase

Front 29

the chain length specificity of 6-12 of an acyl CoA dehydrogenase enzyme is the (very long, long, medium or short) chain enzyme

Back 29

medium

Front 30

what is this?
-most frequently diagnosed of the fatty acid oxidation disorders
-autosomal recessive trait: incidence is 1 in 20,000; 1 in 80 healthy people are carriers
-most common in caucasians of the northern european descent
-accounts for about 1 in 100 SIDS deaths (sudden infant death syndrome)

Back 30

MCAD deficiency

Front 31

MCAD deficiency:
-impairment of oxidation of ... chain fatty acids (6-12 carbons)
-usually presents clinically between ... month and .. year of life following a period of fasting (even overnight fasting) or illness
-symptoms: vomiting, lethargy, muscle weakness, hypoglycemia, hepatomegaly, developmental and behavioral disorders, coma, cardiopulmonary arrest, death
-prevention: frequent feedings, high-carb/low-fat diet (don't let the child go through the night without eating if they have this deficiency)

Back 31

medium
second
second

Front 32

MCAD deficiency:
-20-25% of patients will die with their first episode of illness

-disease management:
-eat ..., avoid ... (babies must feed every 4-6 hours)
-diet high in ..., low in medium and long chain fatty acids
-oral ... supplementation

-North Carolina and Massachusetts (maybe California) offer MCAD deficiency testing as part of their newborn screening programs

Back 32

regularly
fasting
carbs
carnitine

Front 33

during the oxidation steps of beta-oxidation, ... and ... are being generated. These electron carriers can then enter the electron transport chain and form ... through oxidative phosphorylation. This is how energy is being produced when fatty acids are oxidized.

Also remember that the acetyl CoA produced can enter the TCA cycle and generate even more ...

Back 33

FAD(2H) and NADH
ATP

ATP

Front 34

most common fatty acids used for energy through beta-oxidation:
-saturated long chain fatty acids --> ...(C16) and ...(C18)
-monounsaturated fatty acid --> ...(C18:1)
-polyunsaturated fatty acid --> ...(C18:2)

these are the most commonly oxidized fatty acids because they are the most common dietary fatty acids and also most commonly synthesized in humans

Back 34

palmitate and stearate
oleate
linoleate

Front 35

oxidation of unsaturated fatty acids:
-#% of fatty acids in the human diet are unsaturated
-... (C18:1) and ...(C18:2) are the most common
-cis double bonds must be isomerized to trans (isomerase), and the double bond must be reduced (reductase) prior to beta-oxidation

Back 35

50%
oleate
linoleate

Front 36

3 main routes involved in beta-oxidation regulation:
-... (glucagon, epinephrine, beta-corticotropin)
-... (from fatty acid synthesis) (will feed back and inhibit)
-rate of ... utilization and electron transport chain

Back 36

hormones
malonyl CoA
ATP