Biochem Exam 2: Degradation Of Fas

Front 1

what is the largest source of energy in the human body?

Back 1

fatty acids

Front 2

What is the main source of FAs during fasting?
What what three tissues do not use fatty acids during fasting as an energy source?

Back 2

triglycerides

brain, RBC, adipocytes

Front 3

What are the main sources of FAs during the well-fed state?

Back 3

chylomicrons and VLDLs (very low density lipoproteins)

Front 4

where are long-chains stored?

Back 4

in adipose as triglycerides

Front 5

what two things stimulate the release of fatty acid from adipose tissue?

Back 5

epinephrine levels and glucagon/insulin ratio

Front 6

what type of lipase cleaves triglycerides into FAs and glycerol?

Back 6

hormone sensitive lipase

Front 7

what do fatty acids have to be bound to to be transported through the blood?

Back 7

albumin

Front 8

what type of protein transports fatty acids into the cell?

Back 8

a fatty acid binding protein (in the plasma membrane)

Front 9

where are long-chain fatty acids (C12-22) degraded in? and by what enzyme?

Back 9

mitochondria, ER and peroxisomal membranes; long chain acyl CoA synthetases.

Front 10

where are very long chain (C>22) and branched chain fatty acids degraded?

Back 10

peroxisomes
(reduced to medium and short length carnitine derivative, then sent to mitochondria for beta-ox)

Front 11

where are some (medium) C10-C12 fatty acids degraded and via what path?

Back 11

ER and omega oxidation

Front 12

in order to be metabolized fatty acids have to be converted to ________

Back 12

fatty acyl CoA

Front 13

what does the activation of fatty acids require?

Back 13

consumption of 2 high energy phosphate bonds

Front 14

where is acetyl CoA synthetase located?

Back 14

cytosol and mitochondrial matrix

Front 15

what are the three ways fatty acyl CoA can be utilized?

Back 15

energy, storage and membrane lipids

Front 16

how are long chain fatty acids transported into the mitochondrial matrix?

Back 16

carnitine-conjugated form

Front 17

what fatty acid chain length does not require carnitine for mitochondrial transport?

Back 17

medium chain fatty acid and Very long chain

Front 18

there are different isoforms of CPTI for three body parts, what are they?

Back 18

liver, muscle and brain

Front 19

which CTP is on the inner mitochondrial membrane?

which CTP is the rate limiting, committed, and regulated step?

Back 19

CTPII

CTPI

Front 20

what transfers carnitine from the matrix to CTPI?

Back 20

Carnitine acylcarnitine translocase (CAT)

Front 21

Where and what is carnitine synthesized from?

Back 21

synthesized from protein bound lysine, begins in skeletal muscles-->completed in liver and kidney

Front 22

what does the synthesis of carnitine require as a methyl donor?

Back 22

S-adenosyl-mehionine (SAM)

Front 23

where is most carnitine stored?

Back 23

skeletal muscle

Front 24

what can carnitine be used as to accelerate fatty acid oxidation?

Back 24

dietary supplement

Front 25

when do deficiencies in carnitine metabolism usually manifest?

Back 25

during fasting or infections

Front 26

what does a deficiency of carnitine metabolism lead to?

Back 26

inability to degrade long chain FAs results in hypoketotic hypoglycemia (ketone bodies are not produced, glucose is not spared); which leads to elevated blood levels of liver enzymes and ammonia (=liver damage)

?leads to liquid droplet accumulation in liver, heart, and skeletal muscle

Front 27

how do you treat a deficiency of carnitine metabolism?

Back 27

high carb, low fat diet rich in medium chain length fatty acids

Front 28

Lipid droplet accumulation caused by failure to degrade long chain FAs, causes what in the following tissues?
Liver:
Skeletal muscle:
Heart:
Brain:

Back 28

Liver: steatosis (no ketone synthesis)
Skeletal muscle: myopathy, hypotonia, myoglobinuria
Heart: cardiomyopathy, arrhythmeia
Brain: unconsciousness

Front 29

what is wrong in primary carnitine deficiency?

How can you distinguish btwn the diff carnitine deficiencies?

Back 29

lack of carnitine transport into cells

-identified by blood carnitine levels, acylcarnitine levels, enzymatic activity, and genetic testing

Front 30

primary carnitine deifciency creates a _____ plasma carnitine and acylcarnitine levels and _______ carnitine in urine?

Back 30

low; elevated

Front 31

which deficiency in carnitine metabolism is only found in the liver?

Back 31

carnitine palmitoyl transferase IA deficiency

Front 32

carnitine palmitoyl transferase IA deficiency causes : _______ free carnitine plasma levels and _______ acyl (16-18) carnitine

Back 32

elevated; low

Front 33

what two carnitine metabolism deficiencies cause low plasma free carnitine levels and elevated acyl (C16-18) carnitine levels?

Back 33

carnitine-acylcarnitine translocase deficiency and carnitine palmitoyl transferase II deficiency

Front 34

where does beta oxidation occur?

Back 34

mitochondrial matrix

Front 35

in every cycle of beta oxidation, what three forms of energy are generated?
How many ATP are produced per each form?

Back 35

1 FAD(2H), 1NADH, and 1 acetyl CoA

FADH2=1.5 ATP
NADH= 2.5 ATP
acetyl CoA= 10 ATP

Front 36

after each cycle, the length of the fatty acyl CoA decreases by how many carbon(s)?

Back 36

2

Front 37

what does the last cycle of beta oxidation produced due to the even chain length of fatty acids?

Back 37

2 acetyl CoAs

-can enter TCA OR be used for ketone body synthesis in liver only

Front 38

What are the 4 steps of beta oxidation?
What enzyme catalyzes each step?

Back 38

1. Fatty acyl CoA --> trans delta2 fatty enoyl acyl CoA
(via acyl CoA dehydrogenase)
2. trans delta2 fatty enoyl acyl CoA -->
L-beta-Hydroxy acyl CoA
(via enoyl CoA hydratase)
3. L-beta-Hydroxy acyl CoA --> beta-keto acyl CoA
(via beta-hydroxy acyl CoA dehydrogenase)
4. beta-keto acyl CoA--> Acetyl CoA
(via beta-Keto thiolase)

Front 39

what type of bond cannot be processed by beta oxidation?

Back 39

cis double bonds

Front 40

what is the process of beta oxidation in unsaturated fatty acids?

Back 40

beta oxidation proceeds as normal until it reaches a cis double bond and stops. The cis double bond is changed to a trans bond (Enoyl CoA isomerase) and beta oxidation can proceed further.

Front 41

in the beta oxidation of odd chain fatty acids, what is produced in the last cycle?

Back 41

1 acetyl CoA (2 carbons) and 1 propionyl CoA (3 arbons)

Front 42

what is propionyl CoA degraded to in the beta oxidation of odd chain fatty acids?

Back 42

succinyl CoA

Front 43

what can enzyme deficiencies in the degradation of propionyl CoA pathway cause?

Back 43

organic acidemias (propionic or methylmalonyl acidemia, methylmalonyl are intermediates in propionyl CoA degradation)

Front 44

There are 4 diff acyl CoA dehydrogenases, based on chain length. What are two acyl CoA dehydrogenase deficiencies?

Back 44

MCAD deficiency and VLCAD deficiency

Front 45

what does MCAD deficiency cause?

Back 45

sudden death during infancy, elevated (C6-C10)medium chain acylcarnitine levels in plasma, and elevated medium dicarboxylic acids in urine (omega oxidation)

Front 46

what does VLCAD deficiency cause?

Back 46

elevated very long chain acylcarnitine levels in plasma.

Front 47

what is the treatment for MCAD and VLCAD?

Back 47

glucose and carb-rich diet

Front 48

what is an allosetric inhibitor of CPTI?

Back 48

malonyl CoA

Front 49

what type of acids does omega oxidation produce?

Back 49

dicarboxylic

Front 50

T/F
dicarboxylic acids cannot undergo beta oxidation

Back 50

false

Front 51

for the transportation of very long chain fatty acids to peroxisomes, is carnitine necessary?

Back 51

no, its already in a CoA conjugated form

Front 52

how are branched fatty acids (i.e phytanic acid) first oxidized?

Back 52

in the alpha position

Front 53

what is the main difference between peroxisomal beta oxidation and mitochondrial beta oxidation?

Back 53

no FAD(2H) is produced in peroxisomal beta oxidation

Front 54

what does peroxisomal beta oxidation produce instead of FAD(2H)?

Back 54

hydrogen peroxide

Front 55

what is refsum disease deficient in?

Back 55

phytanic acid hydroxylase

Front 56

what does phytanic acid hydroxylase do?

Back 56

alpha oxidation of phytanic acid, necessary for degradation of phyanic acid (a branched chain FA)

Front 57

what are the symptoms of refsum disease?

Back 57

retinitis pigmentosa (leads to blindness), lack of ability to smell, deafness, neuropathy, ataxia, elevated plasma phytanic acid levels

elevated phytanic acid, normal FA levels

Front 58

what are two generalized nervouse system disorders?

Back 58

refsum disease and zellweger syndrome

Front 59

what causes zellweger syndrome (PBR,ZSS)?

Back 59

deficient peroxisome biogenesis

-demylination occurs, elevated C26:0, C26:0/C22;0, C24:0/C22:0 FA and phytanic acid in plasma

Front 60

which one is more serious, zellwegger or refsum?

Back 60

zellwegger

Front 61

where does ketone body synthesis take place?

Back 61

liver (acetyl CoA-->ketone)

(then ketone--> acetyl CoA in peripheral tissues and oxidized in TCA)

Front 62

the ketone body synthesis process involves how many acetyl CoA?

Back 62

2

Front 63

what are the two end products of ketone body synthesis?

Back 63

D-beta-hydroxybutyrate and acetone

3rd ketone body is acetoacetate (not used physiology)

Front 64

ketone body utilization is the inverse of which reaction?

Back 64

ketone body synthesis

Front 65

what regulates the amount of acetyl coa in ketone body synthesis?

Back 65

the rate of beta oxidation

Front 66

what happens when the NADH/NAD ratio is high in ketone body synthesis?

Back 66

the malate-oxaloacetate reaction reverses and acetyl-coa cannot enter the TCA cycle and is used for ketone body synthesis.

Front 67

During fasting, fatty acid degradation in the liver is a prerequisite for the synthesis of _________, used by other tissues for energy production.

Back 67

ketone bodies
(beta-hydroxybutyrate primarily ketone & energy source during fasting, acetoacetate < FA < glucose <<beta-hydroxybutyrate)

Front 68

omega-oxidation (increase/decreases) if beta-oxidation is (deficient/excessive)

Back 68

increases
deficient

Front 69

The produced acetyl CoA and short and medium chain FAs from perioxisomal degradation are transported to the mitochondria as ________

Back 69

carnitine derivatives

Front 70

X-LAD a peroxisomal deficiency is due to__________
and causes____________

Back 70

defective peroxisomal very long chain FA (VLFCA) transporter

causes demylination in NS,
elevated C26:0, C26:0/C22:0 ratio, and C24:0/C22:0 ratio, normal phytanic acid

Front 71

Ketoacidosis can be caused by ____________ and _______________

Back 71

chronic alcohol consumption(TCA is inhibited sending acetyl-CoA to ketone synthesis)
and
type I diabetes (low insulin stops FA degradation & sends acetyl-CoA to ketone synthesis)

Front 72

Hypoketotic hypoglycemies can be caused by what two deficiencies?

Back 72

Deficiencies in carnitine metabolism
Deficiencies in beta-oxidation (ie MCAD)

Front 73

How is beta-oxidation (FA release) regulated)?

Back 73

Inhibited: AMP-PK, malonyl-CoA, NADH, FADH2
(low energy)
activated: insulin, FA
(well-fed)