Fats Flashcards
1
Q
De Novo Lipogenesis
A
- fatty acid biosynthesis
- occurs when glucose is in excess
- acetyl CoA leaves mitochondria as citrate, then is converted back to acetyl CoA in cytosol
- acetyl CoA-> malonyl CoA by acetyl CoA carboxylase
- uses NADPH for energy
2
Q
Acetyl CoA Carboxylase
A
- rate limiting step in de novo lipogenesis (fatty acid biosynthesis)
- inhibited by long chain fatty acids
- activated by citrate
3
Q
Fatty Acid Synthase
A
-puts together units of malonyl coA 2 at a time to form a fatty acid chain
4
Q
Lipoprotein Lipase
A
- takes triglyceride up into adipose tissue to be stored
- degradation of TG stored in chylomicrons and VLDL
- requires apoC-2 as cofactor
5
Q
Fatty Acid Oxidation (Beta Oxidation)
A
- during negative energy state
- stored triglycerides are broken down by hormone sensitive lipase
- taken up by liver and used as substrate in gluconeogenesis
- converted to acyl carnitine to be transported into mitochondria in liver for oxidation
- transported into mitochondria by carnitine palmitoyl transferase 1 (CPT1)
6
Q
Hormone Sensitive Lipase
A
- when insulin is low and counter regulatory hormones are high
- breaks down stored triglycerides
- degrades TG stored in adipocytes
7
Q
Carnitine Palmitoyl Transferase 1 (CPT1)
A
- transports actyl-carnitine into mitochondria in liver to be oxidized
- rate limiting step
- inhibited by malonyl coA
8
Q
Ketogenesis
A
- when insulin is very low and counter regulatory hormones are very high
- during long term fasting
- acetyl coA produced during beta oxidation in the liver can take alternative route to become a ketone body
- occurs in mitochondria
9
Q
HMG CoA Synthase
A
rate limiting step in ketogenesis
-synthesizes HMG CoA
10
Q
Cholesterol Synthesis
A
- synthesized from acetyl CoA through formation of HMG CoA
- HMG CoA is converted to mevalonate
- rate limiting step in HMG CoA reductase - mevalonate converted to cholesterol
- uses NADPH for energy
- liver cell cytosol is major site of cholesterol synthesis
11
Q
HMG CoA Reductase
A
- rate limiting step in cholesterol synthesis
- converts HMG CoA to mevalonate
- regulation:
1. transcriptional depression when HMG CoA is inc. - also SREBP upregulates transcrption
2. translational regulation when cholesterol is inc.
3. half life dec. when cholesterol inc.
4. AMP kinase phosphorylates HMG CoA reductase, inactivating it
12
Q
Glycerophospholipids
A
- specialized lipid
- glycerol backbone and PO4 group
- make up bulk of membrane lipids
- ex. phosphatidylcholine, phosphatidylserine, phosphatidylinositol
13
Q
Sphingolipids: sphingomyelin
A
- ceramide backbone
- contains N atom
- PO4 group with choline
- major structural lipid in nerve tissue
- precursor is ceramide made from fatty acid and serine
14
Q
Glycosphingolipids
A
- ceramide backbone
- sugar residues attached to head group
15
Q
Leukotrienes and Prostaglandins/Thromboxanes
A
- made from arachidonic acid
- COX 1 and 2 are critical enzymes in this synthetic pathway
- inhibited by NSAIDS
16
Q
Lipoproteins- 3 Pathways
A
- particles that contain apolipoproteins and lipids
- how nonpolar lipids like cholesterols and triglycerides and phospholipids travel in blood
1. dietary fat pathway (chylomicron)
2. VLDL pathway
3. HDL pathway
17
Q
Dietary Fat Pathway (Chylomicron)
A
- triglyceride rich particles take dietary fat to muscle/adipose tissue
- made by GI tract from dietary fat
- 10:1 :: triglyceride:cholesterol
- contain apo B48, apoC2, apoE
- triglycerides are broken down by lipoprotein lipase
- not normally present in fasting serum
18
Q
VLDL Pathway
A
- pathway by which triglycerides derived from liver are delivered to muscle and adipose tissue
- 5:1 :: triglyceride:cholesterol
- contain apoB100
- VLDL are metabolized by LPL to form LDL
- most LDL particles are cleared by liver
19
Q
HDL Pathway
A
- transports cholesterol and other lipids from periphery to liver
- reverse transport
- protection against atherosclerosis
- contains apoA1
- ABC-A1 cassette facilitates transport of cholesterol from peripheral tissues to HDL
- LCAT transfers fatty acid
20
Q
Starting Material in Fatty Acid Biosynthesis? Where is it produced?
A
- starting material: Acetyl CoA, produced in mitochondria in glycolysis
- major sources: biosynthesis from small molecules, diet
21
Q
Where does fatty acid biosynthesis occur?
A
- occurs in cytosol
- occurs when dietary calories are in excess
22
Q
What is rate limiting step in fatty acid biosynthesis?
A
- formation of malonyl coA from acetyl coA by acetyl coA carboxylase
- upregulated by citrate
- inhibited by long chain gatty acyl coA
- pathway inc. when insulin is inc.
- pathway dec. when glucagon is inc.
- inhibited by palmitoyl coA
23
Q
What are final products of fatty acid biosynthesis? How do cells utilize these products?
A
- product is palmitic acid (16:0)
- major component of cell membranes, storage form of metabolic energy, precursors for hormones
24
Q
Fatty Acid Structure (Saturated vs Unsaturated)
A
- hydrophobic hydrocarbon chain
- hydrophilic carboxyl group
- longer chain length is more insoluble in water
- components of membrane lipids
- saturated: always trans, no double bonds
- unsaturated: cis, double bond, dec. melting temp
25
Q
Fatty Acid Naming (2 Ways)
A
- ex. 20:4
- numbered beginning with carboxyl carbon
- # before colon indicates # of carbons in chain
- #s listed after colon are position of double bond - numbered beginning with second carbon as a, b, ….
- terminal methyl carbon is always w carbon
- ex. w6= closest double bond to methyl group
26
Q
Essential Fatty Acids
A
- linoleic acid (w6)- precursor of arachidonic acid
- linolenic acid (w3)
- humans cannot make double bonds between carbon 9 and the w end of fatty acid
27
Q
Fatty Acid Elongases
A
- catalyzes the initial condensation step for elongation of saturated or polyunsaturated fatty acids
- occurs in mitochondria
- formation of double bond in fatty acid involves ER membrane
28
Q
Triacylglycerol
A
- synthesized from G3P and fatty acyl coA
- fatty acid on carbon 1 is saturated, carbon 2 is unsaturated, and carbon 3 is either
- major storage form of fatty acid
- synthesized in liver
- packaged with apo B100 to form VLDL for delivery to body
29
Q
Phosphatidylcholine
A
- glycerophospholipid
- along with PE is the most abundant phospholipid in body
- main component in lung surfactant
- serves as reservoir of choline
- present in bile
30
Q
Phosphatidylinositol
A
- glycerophospholipid
- important in signal transduction (becomes IP3 and DAG)
- reservoir for arachadonic acid which is used in PG synthesis
- important in membrane protein anchoring
31
Q
Cholesterol Transport
A
- not metabolized by oxidation, so can only be removed from body by excretion through bile acids
- accumulation in blood vessels-> atherosclerosis
32
Q
Triglyceride
A
-accumulation in blood stream can cause pancreatitis and inc. risk for atherosclerosis
33
Q
Remnant Particles and Intermediate Density Lipoproteins (IDLs)
A
- metabolic byproducts of metabolism of chylomicrons and VLDL
- 1:1 :: triglyceride:cholesterol
- atherogenic
34
Q
Low Density Lipoproteins (LDL)
A
- produced from metabolism of VLDL
- more cholesterol than triglycerides
- very atherogenic
- cleared from circulation by liver
35
Q
ABC-A1
A
- facilitates transport of free cholesterol from peripheral tissues into HDL
- mutation results in Tangiers Disease
36
Q
LCAT
A
- catalyzes the formation of cholesterol esters in lipoproteins
- LCAT is the enzyme that esterifies the free cholesterol on HDL to cholesterol ester and allows the maturation of HDL
- deficiency in LCAT -> low levels of HDL cholesterol-> corneal opacities, renal insufficiency and hemolytic anemia
37
Q
CETP
A
- plasma protein that facilitates the transport of cholesteryl esters and triglycerides between the lipoproteins
- collects triglycerides from VLDL or LDL and exchanges them for cholesteryl esters from HDL, and vice versa
- low levels of this protein-> high HDL levels and live longer than average
38
Q
Apolipoproteins
A
- can form structural backbone of lipoprotein particle, ex. apo B48, apoB100, apoA1
- enzymatic cofactors, ex. apoC2
- ligands for receptors, ex. apoB100, apoE
- clinically significant bc of association with atherosclerosis, ex. apo(a)
39
Q
Sources of Triglycerides
A
- adipose tissue
- muscle
- palmitic acid
- stearic acid
40
Q
Intramuscular Triglycerides
A
- inc. training leads to inc. fat storage in muscle near mitochondria
- also inc. in obesity
41
Q
Fuel Selection as Exercise Intensity Increases
A
- begins with glucose as primary source
- sustained low intensity exercise uses fat oxidation
- inc. intensity uses glucose oxidation
- very high intensity uses lactate production
42
Q
Adaptations with Training
A
- inc. muscle mass
- inc. mitochondrial content
- inc. intramuscular glycogen and triglycerides
- inc. rate of lypolysis, beta oxidation, and lactate clearance
- inc. work capacity and shift to fat as preferred fuel
- inc. lactate clearance
- inc. VO2 max
- better to be fat and fit and thin and unfit to dec. CVD mortality
43
Q
Exercise Recommendations
A
- 2 hrs and 30 mins/week mod. intensity exercise
- or 75 min/week vigorous aerobic activity
- should do muscle strengthening activities that involve all major muscle groups 2 or more days per week
44
Q
Catecholamines
A
- tightly control lipolysis
- bind to b-adrenergic and a2-adrenergic receptors on fat cell membrane-> inc. cAMP-> lipolysis
45
Q
Phospholipase
A
-breaks down phospholipids
46
Q
MCAD Deficiency (medium chain acyl coA dehydrogenase)
A
- most common genetic cause of impaired fat oxidation
- unable to complete beta-oxidation for medium chain fatty acids (C-6-C-10)
- peripheral glucose utilization is increased
- results in buildup of acids
- failure to produce ketone bodies
47
Q
VLCAD Deficiency
A
- similar to MCAD deficiency
- defect in metabolism of fatty acids of longer chain length C-12-C-16)
- milder sx and may appear later in life
- develop muscle soreness or even rhabdomyolysis following exercise
48
Q
CPT-1 Deficiency
A
- CPT-1 is required to carry fatty acids into the mitochondria where beta-oxidation takes place
- defect in fat oxidation and develop fasting hypoglycemia with low ketone levels
- present in infancy following viral illness
- inc. free carnitine, low acyl-carnitine
- inc. ammonia
- tx: constant delivery of dietary carb to prevent hypoglycemia
49
Q
Statin Benefit Groups
A
- clinical ASCVD: high intensity
- LDL-C > 190 without secondary cause: high intensity
- diabetes, age 40-75, LDL-C 70-189: mod or high intensity
- no diabetes, age 40-75 yrs, LDLC 70-189 + 7.5% risk of CVD in next 10 years: mod intensity
50
Q
LDL-C Equation
A
-LDL-C = total cholesterol -(HDL-C + TG/5)
51
Q
Atherosclerotic Risk
A
- age
- male
- african america
- smoking
- HTN
- high total cholesterol
- low HDL
- diabetes
- family hx
- sedentary lifestyle
52
Q
Familial Hypercholesterolemia (FH)
A
- most often defect in LDL receptor
- dec. in LDL removal
- autosomal dominant
- premature death from atherosclerosis
- sx: arcus cornealis (lipid deposits in cornea), xanthelasmas (lipid deposits on eyelid), tendinous xanthoma (Achilles big)
53
Q
Hypertriglyceridemia
A
-normal is
54
Q
Familial Chylomicronemia
A
- LPL deficiency
- APOC2 deficiency
- GPIHBP1 deficiency
- pancreatitis risk
- no premature CHD
- eruptive xanthoma
- lipemia retinalis
55
Q
Familial Dysbetalipoproteinemia
A
- broad beta disease
- inc. triglycerides and/or inc. LDL
- autosomal recessive
- apoE2 rather then E3 or E4
- inc. risk for CHD
- dx: lipoprotein electrophoresis or apo E gentype
- planar/palmer xanthomas on extensor surfaces
56
Q
Tangier Disease
A
- altered ABCA-1 gene
- orange tonsils from accumulation of cholesterol
57
Q
LDL and BP Lowering Diets
A
-DASH, mediterranean
58
Q
HMG CoA Reductase Inhibitors
A
- Statins
- inhibit HGM CoA Reducatse
- dec. hepatic pool of free cholesterol
- inc. expression of LDL receptors on cell membranes
- inc. catabolism of VLDL and LDL
- dec. LDL concentration
- with doubling of statin dose: LDL falls by 6%
- side effectsL abnormal AST/ALT, myopathy, congitive impairment, new onset T2DM
59
Q
Intestinal Acting Cholesterol Agents
A
- bile acid sequestrants: cholestyramine, colestipol, colesevelam
- inhibition of cholesterol absorption: plant stanol esters and sterol esters
- selective choesterol absorption inhibitors: ezetimibe (blocks cholesterol absorption at brush border)
60
Q
PCSK9 Inhibitors
A
- monoclonal antibodies that restore LDL receptor function
- adverse: drug induced antibodies, allergy
61
Q
Management of Very High LDL
A
-max statin, ezetimibe, resin, fenofibrate, niacin
62
Q
Drugs Used to Lower Triglycerides
A
- fibrates
- omega 3 fatty acids
- nicotinic acid
- statins
63
Q
Niacin Contraindications
A
- severe skin rash
- liver disease
- hyperuricemia/gout
- peptic ulcer or IBD
- impaired glucose tolerance
64
Q
How to raise HDL?
A
- exercise (10%)
- sustained weight loss
- alcohol
- smoking cessation
65
Q
Apo E Function
A
- mediates remnant uptake
- on everything except LDL
66
Q
ApoA-1 Function
A
- activates LCAT
- on HDL
67
Q
ApoC-2
A
- lipoprotein lipase cofactor
- present in VLDL, chylomicrons, HDL
68
Q
ApoB-48
A
- mediates chylomicron secretion
- present in chylomicrons
69
Q
ApoB-100
A
- binds LDL receptor
- present in VLDL, IDL, LDL
