Brainscape's Knowledge GenomeTM

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


See full index

Fuel Metabolism > Lipid Metabolism > Flashcards

Lipid Metabolism Flashcards

1
Q

6 Major Classes of Lipids

A
  • Fatty acids
  • Triglycerides
  • Ketones
  • Cholesterols
  • Phospholipids
  • Sphingolipids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Structure of Major Lipids Classes

A
  • Fatty acids - building blocks
  • Triglycerides- glycerol + 3 FAs
  • Ketones- only 4 carbons so soluble - formed when FAs degrade - acetoacetate and beta-hydroxybutyrate
  • Cholesterols- has sterol nucleus (4 rings) with hydoxyl group and h8-C side chain; but most in body is cholesterol ester which is cholesterol + single FA chain
  • Phospholipids- glycerol backbone w/ 2 FA chains and 1 phosphoric acid chain
  • Sphingolipids - contain sphingosine derived from FA and serine (has 1 amino group and 2 hydroxyl groups)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Function of Major Lipid Classes

A
  • Fatty acids - metabolic fuel (esp for skeletal and heart muscle); building blocks/precursors for other lipids
  • Triglycerides- storage and transport form of FAs
  • Ketones- fuel for skeletal muscle, heart, kidney and brain
  • Cholesterols- in plasma membrane; makes steroids, vitamin D and bile acids
  • Phospholipids- membrane building block; signal transduction pathways; storage site for poly-unsaturated FAs
  • Sphingolipids - in membranes; surface antigens
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How does the insulin:glucagon ration affect interconversion of lipids?

A
  • Dietary triglycerides –> triglycerides –> FAs –> acetyl CoA –> cholesterol or TCA cycle
  • Insulin = promotes synthesis of fatty acids and storage of lipids (shunt acetyl CoA to fatty acids and triglycerides instead of TCA cycle)
  • Glucagon = promotes mobilization and oxidation of lipids and synthesis of ketones (shunt FAs and tricglycerides to acetyl CoA)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Pancreatic Lipid Digestion Enzymes + Reactions (3)

A
  • Pancreatic lipase (TG–> FA + DG then acts on DG –> MG + FA) **requires colipase
  • Cholesterol Esterase (cholesterol esters –> cholesterol + FA)
  • Phospholipase A2 (phospholipid –> lysophospholipid + FA)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the primary emulsification agent and why?

A

bile salts!

- Converts fat globules to smaller and smaller droplets so that they are more easily attacked by enzymes (inc surface area)
- Works b/c bile salts are amphipathic (both hydrophilic and hydrophobic) and because low pKa of amino side chain
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the key enzymes and reactions of dietary lipid repackaging?

A
  • 1- activate FAs via fatty acyl-CoA synthetases (FA + CoA + ATP –> fatty acyl CoA + AMP + PP)
  • 2- esterification rxns via fatty acyl CoA transferase for TGs and ACAT for cholesterol esters
    • MG + FA-CoA –> DG + FA-CoA –> TG
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Effect of bile salt deficiency

A

.excrete lipid in feces because cannot emulsify and absorb (steatorrhea- lipids in feces - chalky or clay-colored)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Effect of colipase deficiency

A

severe weight loss because metabolic fuel lost in feces (needed for pancreatic lipase to work)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Effect of apoprotein B -48

A

.needed for chylomicron assembly so w/o it fat accumulates in intestinal cells and liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Effect of fatty acyl CoA synthetase

A

cannot activate FAs once in intestinal cell …no fatty acyl CoA for esterfication reactions…cholesterol and MGs accumulate in intestine and there is a lack of cholesterol ester and TGs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Effects of Lipid Malabsorption (5)

A
  • Leads to inability to absorb fat-soluble vitamins
    • no Vit A - night blindness
    • no Vit D - osteoporosis
    • no Vit E - anemia
    • no Vit K - defective blood clotting
  • Also leads to inability to maintain weight
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What happens if you have a diet rich in medium to small chain triglycerides?

A
  • medium and short chain FA (about 10 carbons or less) are released directly into portal blood where they are bound by albumin and transported directly to liver
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Lipoprotein Properties

A
  • Chylomicrons - largest (why they enter lymph not circulation) - least dense; most lipid content
  • VLDL - next largest, least dense and most lipid
  • LDL - next least dense; next most lipid content; highest cholesterol content
  • HDL - smallest and highest density; about 50:50 lipid to protein content; next highest cholesterol content to LDL
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the apoprotein content of each class of glycoproteins?

A
  • Chylomicrons- B C E
  • VLDL- B C E
  • IDL- B C E
  • LDL-B
  • HDL- A C E
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the source of each class of glycoproteins?

A
  • Chylomicrons - intestine
  • VLDL - liver
  • IDL - from VLDL in plasma
  • LDL - from IDL in plasma
  • HDL - liver or intestine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the general function of each class of glycoproteins?

A
  • Chylomicrons - transport TGs to peripheral tissues
  • VLDL- transport TGs to peripheral tissues
  • IDL- transport TGs + LDL precursor
  • LDL - transport cholesterol to peripheral tissues
  • HDL- reservoir of apoproteins + brings cholesterol back to liver
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Apoprotein Functions

A
  • Apo A- stim LCAT for reverse cholesterol transport by HDL
  • Apo B- binds/recognizes LDL receptors on cells
  • Apo C- activates LpL (lipoprotein lipase)
  • Apo E- binds/recognizes remnant receptors on liver (remnant recycling in liver)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

LpL (function, location, regulation)

A
  • Function - degrades TGs –> FAs + glycerol (depletes chylomicrons, LDLs and IDLs of their TGs-> now call “remnant”) - So fatty acids can then be delivered to given cells
  • Location - in luminal wall of capillaries outside cell (esp in adipose, skeletal muscle and cardiac muscle)
  • Regulation -
    • All isozymes ACTIVATED by apo C-II
    • LpL in adipocytes specifically responds to insulin –> inc fat storage in adipose cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Lipoprotein Lipase v Hepatic Lipase

A

both extracellular enzymes that hydrolyze

  • LpL - works on chylomicrons, LDLs and IDLs and have little affinity for IDLs because as they shrink, apo C-II is transferred back to HDLs
  • Hepactic Lipase- works on IDLs only (converts IDLs –> LDLs)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Steps of Reverse Transport of Cholesterol

A

1-Uptake of cholesterol by HDL (mediated by ABCA-1)

2-Esterification of HDL cholesterol by LCAT (stim by apo A)

3-Transfer of cholesterol ester from HDL to lipoprotein remnants

- Mediated by CETP or apo D
- "indirect path"
- These now full remnants cleared by liver

OR Transfer of HDL cholesterol esters to tissues via scavenger receptor B1

- HDL binds SRB1 receptors on liver or steroidogenic tissues 
- HDL not endocytosed (recycled)
- "direct path"
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

LDL receptors v remnant receptors

A
  • LDL receptors- on extra hepatic tissues (deliver cholesterol to them); also some on liver to get cholesterol from indirect path
    • Apo B binds LDL receptors
  • Remnant receptors-on liver; to recycle VLDL remnants (IDL)
    • Apo E binds remnant receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

LDL receptors v scavenger receptors

A

LDL receptors- (75%) on extra hepatic tissues (deliver cholesterol to them); also some on liver to get cholesterol from indirect path
*Regulated by cholesterol concentration

  • Scavenger Receptors - (25%) low affinity for LDL but high affinity for oxidized LDL; located on macrophages
    • Not regulated by cellular concentration of cholesterol so as cholesterol accumulates macrophages –> foam cells (over time foam cells form atherogenic plaques)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

2 Fates of IDLs

A
  • 1- Converted to LDL by hepatic lipase (return apo E back to HDL pool)
  • 2- Internalized by liver (apo E of IDL binds remnant receptors on liver)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Role of ABCA1

A

ABCA-1 mediates the transfer of unesterified cholesterol from cell to a lipid-poor HDL (nascent HDL)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

ABCA1 Deficiency

A

**Deficiency in ABCA-1 –>deficiency in HDL –> dec cholesterol and inc TGs in blood –> yellow-orange enlarged tonsils (Tangier’s Disease)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What defect underlies familial hypercholesterolemia?

A
  • Also known as Type II hyperlipoproteinemia
  • Inherited defect in LDL receptor –> cannot get cholesterol into cell so high cholesterol levels in blood
  • Most common disease in lipid metabolism
28
Q

Cholesterol Structure

A
  • 4 ring nucleus + 8C side chain + hydroxyl group

- Cholesterol ester - hydroxyl becomes ester

29
Q

What is the primary substrate of cholesterol synthesis? Key Intermediates?

A

3 Acetyl CoA (primary substrate) —> HMG-CoA

HMG-CoA —> …2 isoprene units (5 carbons) —> squalene (30 carbons)–> cholesterol

30
Q

What is the rate-limiting step in cholesterol synthesis and how is it regulated?

A
  • Rate limiting step = HMG-COA Reductase

NADPH + HMG-CoA —> mevalonate + NADP+

  • Synthesis of enzyme repressed by cytosolic cholesterol
  • Diurnal variation (peaks 6 hrs after dark and min 6 hours after light)
  • Act by insulin and thyroid hormone
  • Deact by glucagon and cortisol
  • Modified via phosphorylation (deactivated when phosphorylated)
31
Q

How does liver contribute to cholesterol balance?

A
  • Receives it from diet via chylomicron remnants and from cells via reverse transport (HDL)
  • De novo synthesis
  • Repackages it and sends it off in VLDL
  • Converts it to bile acids (secreted or reabsorbed
32
Q

How would a genetic deficiency in apoprotein B cause hypercholesterolemia?

A

If deficiency in cell surface receptors for apoprotein B the cell would not be able to bind and endocytose the LDL and acquire cholesterol so cholesterol would stay in blood rather than enter peripheral tissues —> hypercholesterolemia

LDL receptors bind apoprotein B on LDL

33
Q

ACAT v LCAT

A
  • Both esterify cholesterol
  • ACAT is in extra hepatic cells for cholesterol storage
  • LCAT is w/ HDL helping w/ reverse transport of cholesterol
34
Q

Statins and Cholestyramine

A
  • Statins - drugs that inhibit the activity of HMG-CoA reductase to decrease cholesterol production
  • Cholestryamine- drug that binds to bile salts in the GI tract and are excreted in feces; prevents reabsorption of these bile acids so inc amount of cholesterol excreted from body
35
Q

Where is cholesterol converted to bile acids?

A

LIVER (cytoplasm?)

36
Q

What is the rate-limiting step in bile acid production?

A

Rate limiting step - cholesterol-7-alpha-hydroxylase (hydroxylation at B-7)

Inhibited by cholic acid (one of the major bile acids)

37
Q

Bile Acids v Bile Salts

A

Carboxyl group of bile acid side chain forms amide bond w/ glycine or taurine —> bile salts (AKA conjugated bile acids)

**Lower pKa of side chain

38
Q

Enterohepatic Circulation of Bile Acids

A
  • Only 5% of bile is excreted; rest is reabsorbed
  • Bile acids secreted from liver during digestion; then reabsorbed in lower small intestine; then released back into portal circulation (bound to albumin) —> liver
39
Q

What is the role of the citrate shuttle?

A
  • Acetyl CoA is made in mito but needed in cytoplasm for synthesis so…use citrate shuttle
    • Citrate from TCA cycle (made by citrate synthase) is sent across IMM —> cytoplasm then…
    • Citrate + ATP + CoASH —> acetyl CoA + OAA + ADP + P (via citrate lyase)
40
Q

What is the rate-limiting step in FA synthesis and how is it regulated?

A

acetyl CoA carboxylase

step that makes the malonyl CoA substrate

Acetyl CoA + HCO3- + ATP —> malonyl CoA

Requires biotin and ATP
Act by citrate
Inhibited by palmitoyl CoA
Inactivated by phosphorylation

41
Q

How does insulin affect FA synthesis?

A

Insulin promotes FA synthesis; activates PP1 which would remove P from acetyl CoA carboxylase

42
Q

What substrates are required for FA synthesis? How are they made?

A

Acetyl CoA (from citrate shuttle)

NADPH (pentose phosphate path OR OAA —> Malate–> Pyruvate + CO2 + NADPH via malate DH and malic enzyme)

Malonyl CoA (Acetyl CoA + HCO3- + ATP —> malonyl CoA via acetyl CoA carboxylase)

43
Q

Stoich of FA Synthesis

A

14H+ + acetyl CoA + 7 malonyl CoA + 14 NADPH —> palmitoyl CoA + 7CO2 + 7CoA + 14NADP+ + 7H2O

44
Q

Citrate Synthase

Citrate Lyase

Malate DH

Malic Enzyme

A

Makes citrate in TCA cycle

Citrate + CoASH –> acetyl CoA + OAA

OAA –> malate

Malate –> pyruvate + NADPH

45
Q

FAS Enzyme + 4 Core Reactions

A

4 core reactions of elongation

- Condensation -lose 1 C as CO2 -end w/ 4C product
- Reduction - use NADPH
- Dehydration -remove H20
- Reduction - use NADPH * **Then prime the 4C product and another malonyl CoA and REPEAT
46
Q

Role of ACP and what is its cofactor?

A

(acyl carrier protein)

thiol groups

primes the acetyl and malonyl groups (acts as scaffold for activating the acetyl CoA and malignly CoA)

47
Q

FA Synthesis in Liver v Mammary

A

In mammary gland, make decanoic acid instead of palm acid; only 10C chain so easier for baby to digest; does not need to be shuttled by chylomicron but can be sent directly into portal circulation

48
Q

How are FAs converted to TGs in adipose tissue?

A
  • Once FAs are taken into cell they are converted to fatty acyl CoA
  • Transfer FAs to C1 and C2 of glycerol-3-P then remove phosphate -> DG; then add another FA to 3-OH —> TG
49
Q

How is glucose involved in TG synthesis in adipose tissue?

A

Glucose is required to give you the G3P (glycerol-3-P) backbone glycolysis intermediate

50
Q

Phospholipid Structure

A

Glycerol backbone w/ 2 long chain FAs and 1 phosphoric acid

51
Q

5 Classes of Phospholipids

A
  • Phosphatidic acid
  • Serine
  • Ethanolamine
  • Choline
  • Inositol
52
Q

Phospholipid Functions

A
  • Structural component of membranes (lipid bilayer)
  • Enzyme activation
  • Second messenger signaling
  • Lung function - major component of surfactant
  • Detergent function in intestine and gall bladder - component of bile (too much phospholipids in bile —> gallstones)
53
Q

How are FAs mobilized from TGs in adipose tissues?

A
  • 3 Triacylglycerol Lipases- 3 enzymes that work together (inside cell)
    - ATGL (triacylglycerol —> FA + diacylglycerol)
    - HSL (diacylglycerol —> FA + monoacylglycerol)
    - MGL (monoacylglycerol —> FA + glycerol)
54
Q

What tissues use FAs as fuel? Which cannot and why?

A

mainly used by liver, muscle, heart and kidney (IN MITO) but ALL tissues can use FAs as fuel except…

- Brain- FAs cannot cross blood brain barrier
- RBCs- no mito
55
Q

What 2 proteins have high affinity for free FA?

A
  • Albumin- when in blood- bound noncovalently

- FABP- intracellular (once FA is in cell it binds FABP then is converted to fatty acyl CoA)

56
Q

Carnitine Shuttle

A
  • Carnitine Shuttle
    • Used to get fatty acyl CoA across IMM
    • OUTSIDE MATRIX- CAT I or CPT I (fatty acyl CoA + carnitine —> CoA + fatty acyl-carnitine)
    • Then fatty acyl-carnitine crosses IMM
    • INSIDE MATRIX- CAT II or CPT II (Fatty acyl-carnitine + CoA —> Fatty acyl-CoA + carnitine)
    • Translocase replaces carnitine to outside matrix
57
Q

How much ATP is made from full oxidation of palmitic acid?

A

129!

7 (3 ATP/NADH) = 21
7(2 ATP/FADH2) = 14
8 (12 ATP/acetyl CoA) = 96 …=131
- If you include complete oxidation of palm acid (so had to turn palm acid into palm CoA) then that cost 2 ATP so …=129

58
Q

Carnitine Deficiency + Causes

A
  • Carnitine Def- cannot get fatty acyl CoA into mito matrix so no FA oxidation (**same thing happens if CTP-I deficiency)
  • Can be caused by certain drugs that are low molecular weigh organic acids and form acyl carnitines that are excreted from body
59
Q

Peroxisome Oxidation v Mito Oxidation

A
  • Used for very long chain FAs and branched chain FAs
  • Very Long Chains…
    • Uses isozymes of mito oxidation
    • Less energy yield than mito oxidation b/c FADH2 made in first step is regenerated by O2 to form hydrogen peroxide so it does not go on to make ATP
  • Branched Chains…
    • Cannot undergo beta oxidation b/c beta carbon has methyl group branch; hydroxylation at alpha group instead
      • Uses alpha-hydroxylase
60
Q

Refsum’s Disease

A

Genetic def in alpha hydroxylase so cannot oxidize branched chain FAs

- retinitis pigmentosa, hearing loss, peripheral neuropathy, ataxia
- Limit diet - no dairy, beef, lamb (phytanic acid)
61
Q

Zellweger Syndrome

A
  • absence of peroxisomes —> accumulation of very long chain FAs and branched chain FAs
    • Fatal by age 2; brain kidney and liver damage
62
Q

What is the most prevalent lysosomal storage disorder? How is it treated?

A
  • Gaucher’s Disease - sphingolipid disorder (usually in membranes and myelin of neurons)
  • Treated w/ enzyme replacement (recombinant glucocerebrosidase) but very expensive
63
Q

Ketone Synthesis

A
  • IN LIVER MITO
  • 2 acetyl CoA —> acetoacetyl-CoA —> HMG CoA —> acetoacetate beta-hydroxybuterate
  • Thiolase, HMG-CoA Synthase, HMG-CoA Lyase
64
Q

Ketone Oxidation

A
  • Oxidation
    • ONLY IN NON-LIVER TISSUES MITO
    • beta-hydroxybutyrase -> acetoacetate + succinyl CoA —> acetoacetyl-CoA —> 2 acetyl CoA
    • BetaHOB dehydrogenase, SCOT, thiolase
65
Q

How/when are ketones used?

A

Provide fuel for muscles and brain during starvation (prevents you from breaking down protein in your muscle)

  • Stim by dec in insulin/glucagon ratio (so during fasting/starvation)
  • *or in people w/ diabetes (no insulin)

Fuel Metabolism (6 decks)

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