Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

SFM > Lipid Metabolism > Flashcards

Lipid Metabolism Flashcards

1
Q

What are the 3 main functions of lipids?

A
  • fuel storage
  • structural components
  • signaling molecules

(other roles: insulation, generating heat, fat digestion)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the major source of carbon for fatty acid synthesis?

A

dietary carbohydrates (that is why eating high amnts of sugar/carbs makes you “fat”)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Where does fatty acid synthesis occur?

A
  • primarily liver
  • also adipose tissue, brain, kidneys, lactating mammary glands
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the 3 major steps in fatty acid synthesis?

A
  1. cytosolic entry of acetyl CoA (made in mito matrix, makes it difficult to synthesize fatty acids)
  2. generation of malonyl CoA (acetyl CoA carboxylated to malonyl CoA, most important substrate in FA synthesis, rate limiting reaction)
  3. fatty acid chain formation (fatty acid synthase incorporates acetyl CoA and malonyl CoA into palmitate)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How does acetyl CoA move from mitcochondria to cytoplasm during fatty acid synthesis? (3 steps)

A
  1. acetyl CoA condensed with oxaloacetate (OAA) to form citrate (citrate synthase)
  2. citrate transported from mito to cytosol (citrate transporter)
  3. citrate coverted back to acetyl CoA and OAA (citrate lyase)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How is OAA regenerated during first step in fatty acid synthesis? (3 steps)

A
  1. OAA reduced to malate (malate dehydrogenase)
  2. malate transported to mito by malate-α ketoglutarate, then oxidized to OAA by malate dehydrogenase
  3. CYTOSOLIC malate converted to pyruvate, pyruvate transported to mito by pyruvate transporter, carboxylated to OAA by pyruvate carboxylase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the rate limiting step in fatty acid synthesis?

A
  • conversion of acetyl CoA to malonyl CoA by carboxylation (acetyl CoA carboxylase (ACC))
  • ATP is used for energy, biotin needed as co-factor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How is acetyl CoA carboxylase regulated during fatty acid synthesis?

A
  • activated by: citrate, insulin
  • inhibited by: glucagon, epinephrine, high AMP, palmitate, PUFA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How does malonyl CoA regulate fatty acid synthesis and degradation?

A
  • it inhibits carnitine acyltransferase (rate limiting step in degradation)
  • prevents degradation and synthesis from occurring simultaneously
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How is the fatty acid chain formed during fatty acid synthesis?

A
  • two carbon units from malonyl CoA are sequentially added to chain in 7 reactions within fatty acid synthase (FAS) complex that forms palmitate (16:0)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the FAS complex within fatty acid synthesis? (3 attributes)

A
  • multi-enzyme complex
  • 2 identical dimers
  • each dimer: 7 enzymes, with 1 acyl carrier protein (ACP) that has a flexible “arm” of phosphoantetheine group (Pan-SH)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the reactions catalyzed by FAS complex in fatty acid synthesis? (4)

A
  1. acetyl CoA and malonyl CoA are condensed to β-ketoacyl group (CONDENSATION)
  2. β-ketoacyl group reduced to β-hydroxyl group (REDUCTION)
  3. β-hydroxyl group dehydrated to trans-enone group (DEHYDRATION)
  4. trans-enone group reduced to 4-C fatty acyl group (REDUCTION)

*6 more cycles of this occurs until a 16-C fatty acyl group is formed (palmitate) and released

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the source of NADPH during fatty acid synthesis? (2 main)

A
  • malic enzyme converts malate to pyruvate in the cytosol along with 1 NADPH
  • pentose phosphate pathway: oxidative phase yields 2 NADPH, non-oxidative G6P can generate up to 12 NADPH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the 3 main regulation points during fatty acid synthesis?

A
  1. ATP citrate lyase converts citrate to acetyl CoA (in cytosol)
  2. acetyl CoA carboxylase converts acetyl CoA to malonyl CoA
  3. fatty acid synthase, the complex that links chains of malonyl to create the fatty acids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How is ATP citrate lyase regulated during fatty acid synthesis?

A
  • stimulated by phosphorylation (phospho active form)
  • gene expression induced by glucose/insulin
  • gene expression inhibited by polyunsaturated fatty acids (PUFAs) and leptin

*AKA: your body will not undergo fatty acid synthesis if there are too many already OR if you are hungry and needs the fuel/energy for other things

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How is acetyl CoA carboxylase regulated during fatty acid synthesis?

A
  • rate limiting step of FA syn
  • mononer / dimer inactive, polymer active
  • citrate (+) increases regulation, long chain FA’s (-) (palmitate) inhibit
  • DEPHOS FORM ACTIVE, PHOS FORM INACTIVE
  • insulin (+) activates protein phosphatase (dephos ACC)
  • epinephrine (-) and glucagon (-) activate protein kinase A (phos ACC)
  • AMP (-) activates AMP kinase (energy sensor)
  • gene expression (+) high carb/low fat diet
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How is fatty acid synthase (FAS) regulated during FA synthesis?

A
  • phosphorylated sugars (+)
  • induction / repression at gene level:
  • insulin and glucocorticoid hormones (+)
  • high carb/low fat diet (+)
  • high fat diet / starvation (-)
  • high PUFA (-)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How and where are long chain fatty acids (longer than palmitate) synthesized?

A
  • location: smooth ER and mitochondria
  • lengthened by 2 carbons at a time, NADPH is reducing power
  • smooth ER uses malonyl CoA as carbon donor, mito use acetyl CoA as carbon donor

*reqiured by brain cells

19
Q

How are fatty acids made to be unsaturated?

A
  • double bonds are added in the smooth ER by NADPH (or NADH) and oxgygen
  • catalyzed by acyl CoA desaturases (humans have 4)
  • desaturases can add dbl bonds from carbons 4-10, but CANNOT add past that or from the methyl end (omega end)
  • creates the need for humans to injest essential fatty acids (omega 3 and omega 6)
20
Q

What are the essential fatty acids and why can’t humans synthesize these types of FA’s themselves?

A
  • linoleic acid (18:2 omega-6): makes arachidonic acid (20:4), a precursor for eicosanoids (prostaglandins, leukotrienes, and thromboxanes)
  • linolenic acid (18:3 omega-3): makes eicosapentanoic acid (EPA) (20:5) and docosahexanoic acid (DHA) (22:6)
  • humans cannot synthesize these FA’s because they can only add dbl bonds from carbons 4-10, and cannot add from methyl end
21
Q

What is the major storage form of fatty acids and why is it so energy rich lb for lb compared to glucose?

A
  • triacylglycerols (TAGs)
  • contains more energy than glucose lb for lb (6.75x more) because they can be tightly packed, while glucose cannot
22
Q

What are the 3 main sources of triacylglycerols?

A
  1. dietary (processed in intestinal cells)
  2. de novo (in hepatocytes)
  3. de novo (in adipocytes)
23
Q

How does TAG synthesis occur in intestinal cells?

A
  • dietary TAGs are broken down by intestinal lumen
  • intestinal cells resynthesize TAGs using MAG backbone and adding 2 free FAs
  • TAGs are then package with apolipoproteins and other lipids into a chylomicron
  • chylomicrons released into lymphatic system, enter blood via throcic duct

* TAG synthesis (+) in intestinal cells by dietary TAGs

24
Q

How are TAGs synthesized de novo in the liver?

A
  • glucose and glycerol form glycerol-3-phosphate (G-3-P) via different pathways
  • G-3-P backbone
  • free FA added to G-3-P to form TAGs
  • TAGs packed with apolipoproteins and lipids to form VLDL (released into blood)

* TAG synthesis (+) in liver by excess carbs

25
Q

How are TAGs synthesized de novo in adipocytes?

A
  • similar to liver
  • glucose (from glycolysis) forms G-3-P which is, again, used as backbone for TAGs
  • FFAs (from breakdown of chylomicrons and VLDL) by capillary lipoprotein lipase are added to G-3-P to form TAGs
  • TAGs are stored in adipocytes

* TAG synthesis (+) in adipocytes by excess carbs and fats

26
Q

What are the 4 major lipases involved in breakdown of TAGs?

A
  1. adipose triglyceride lipase (ATGL): newer finding obtained from HSL knockout mouse
  2. hormone sensitive lipase
  3. lipoprotein lipase
  4. monoacylglycerol lipase
27
Q

How is HSL regulated during TAG breakdown?

A
  • regulated by phosphorylation
  • phos active, dephos inactive
  • hunger (glucagon) / exercise (epinephrine) (+): both of these phosphorylate HSL
  • fed status (insulin) (-): dephos HSL (via PP1)
28
Q

How does perilipin play a role in breakdown of TAGs?

A
  • controls phyiscal access to HSL
  • perilipins phosphorylation by PKA (+)
  • overexpression of perilipin 1 inhibits lipolysis, knock out has converse effect

*obesity treatment target

29
Q

Why must the carnitine shuttle be used during fatty acid oxidation?

A
  • short and medium chain FAs can diffused into mitochondria, however medium, long, and very long chain FAs cannot, thus they needed to be transported in the form of fatty acyl CoA (outer membrane) and fatty acyl carnitine (inner membrane)
30
Q

What are the 4 enzymes in the caranitine shuttle of fatty acid oxidation and what are their general roles?

A
  1. fatty acyl CoA synthetase: cytosol side, activates LCFAs w/ ATP, forms thioester bond to create fatty acyl CoA
  2. carnitine palmitoyltransferase I (CPT-1): RATE LIMITING STEP, intermembrane space, transfers fatty acyl from CoA to carnitine to form fatty acyl carnitine, inhibited by malonyl CoA (FA synthesis)
  3. carnitine-acylcarnitine translocase (CACT): moves FA-carnitine into inner mito and moves carnitine out
  4. carnitine palmitoyltransferase II (CPT II): inner mito membrane, transfers fatty acyl from FA-carnitine to CoA, forms FA-CoA
31
Q

What are the products of fatty acid oxidation? (3)

A
  1. acetyl CoA (enters TCA cycle)
  2. FADH2 (electrons to CoQ/ubiquinone of ETC)
  3. NADH (electrons to complex I of ETC)
32
Q

What are the 4 steps of β-oxidation?

A
  1. oxidation of fatty acyl CoA to trans fatty enoyl CoA: acyl CoA dehydrogenase (ACAD); produces FADH2 that generates 2 ATP in ETC
  2. hydration of trans fatty enoyl CoA to β-hydroxyacyl: enoyl CoA hydratase
  3. oxidation of β-hydroxyacyl to β-ketoacyl CoA: 3-hyoxyacyl CoA dehydrogenase; produces NADH that generates 3 ATP in ETC
  4. thiolysis of β-ketoacyl CoA to fatty acyl CoA: acetyl CoA acetyltransferase (β-keo thiolase)

* THIS IS REPEATED MULTIPLE TIMES UNTIL FA IS BROKEN DOWN INTO ACETYL COA

33
Q

How many ATP does β-oxidation of palmitate (C16) generate?

A

106 net ATP

34
Q

How are odd number FA’s oxidized? (4 steps)

A
  1. metabolized normally until propionyl-CoA remains (3C)
  2. propionyl-CoA is carboxylated via ATP to methylmalonyl-CoA (propionyl CoA carboxylase)
  3. methylmanlonyl-CoA is converted to succinyl-CoA (methylmalonyl CoA mutase)
  4. succinyl-CoA enters TCA cycle
35
Q

How are unsatured FA’s oxidized? (3 general steps)

A
  1. metabolized nomrally until unsaturation is reached
  2. reductase reduces double bond
  3. isomerase moves disruptive bond
36
Q

How are VLCFAs oxidized?

A
  • they are oxidized in the peroxisomes
  • once fatty acyl CoA is n<20, the molecule is sent to mito for β-oxidation
  • high potential electrons are transferred to O2 (FAD containing acyl CoA oxidase), which produces H2O2, that is converted by catalase to H20 and O
37
Q

What are the disorders associated with defects in peroxisomes? (4)

A
  • Zellweger syndrome: biogenesis
  • infantile Refsum disease: assembly
  • X-linked adrenoleukodystrophy: transport of VLCFAs into peroxisome
  • adult Refsum disease: degradation of phytanic acid
38
Q
  • disorder that impairs FA β-oxidation of MCFAs
  • autosomal recessive
  • secondary carnitine deficiency, excessive excretion of MCA carnitines in urine
  • sx: elevated levels of ammonia (C8 FA), metabolic acidosis (ω-oxidation)
  • patients depend on glucose for energy, gluconeogenesis impaired due to low ATP and low acetyl CoA levels
  • hypoglycemia/sudden death, likely brought on by periods of fasting/vomiting
  • may be associated with SID
  • good pronosis if diagnosed prior to onset of sx
  • tx: avoid fasting and other situations where body relies on β-oxidation of FA
A

MCAD (medium chain acyl coenzyme A dehydrogenase) deficiency

39
Q

What are the 3 ketone bodies?

A
  1. acetoacetate
  2. β-hydroxybutyrate
  3. acetone

(water-soluble, acidic, produced in liver only)

40
Q

How are ketone bodies formed?

A
  • 2 acetyl CoA converted to acetoacetyl CoA by acetyl CoA acetyl transferase (liver)
  • that is converted to HMG CoA (liver)
  • that is converted to acetoacetate by HMG CoA lyase (liver)
  • acetoacetate sponatenously reacts to form acetone (exhaled/excreted in urine)
  • acetoacetate converted to β-hydroxybutyrate
  • both are transferred via blood to brain (cannot be used by RBCs)
  • β-hydroxybutyrate is converted back to acetoacetate (brain, NADH formed to use in ETC)
  • that is converted to acetoacetyl CoA, then 2 acetyl CoAs to be used in TCA (brain)
41
Q

How are fuel supplies used in the body during fasting situations?

A
  • 1-3 hours: glucose, then glycogen stored in muscle/liver
  • gluconeogenesis in liver
  • 1 day: TAGs stored in adipose tissue, broken down to FFA undergoing β-oxidation
  • 3 days: ketone bodies in liver and protein in muscle broken down
  • glycerol (TAGs) and glucogenic amino acids (proteins) enter gluconeogenesis (brain and RBCs)
  • 1-2 weeks: brain switches to ketone bodies
  • 2-3 months: TAGs depleted, proteins main source
  • 3 months+: coma and death
42
Q
  • occurs when glucagon/insulin ratio is increased, carb metabolism impaired, favors FA breakdown
  • inc acetyl CoA in mito, inc gluconeogenesis (reduced oxaloacetate)
  • inc ketone bodies (acetoacetate and β-hydroxybutyrate) which causes acidosis, these are excreted via urine
  • acetone exhaled via breath gives fruity odor (uncontrolled diabetes
A

pathological ketoacidosis

43
Q
A

SFM (21 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions