Lipids Flashcards
0
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Function of Lipids
A
Major source of energy Provide hydrophobic barrier Serve as coenzymes, regulators Hormones Mediators of inflammation
1
Q
Group of compounds related by certain physical properties: Insoluble in water, Soluble in nonpolar solvents
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Lipids
2
Q
Amphipathic; have both hydrophilic and hydrophobic groups; enables formation of bilayers
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Phospholipids
3
Q
Long chains of carboxylic acids
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Fatty acids
4
Q
Degree of Saturation: Contain 0 double bond
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Saturated Fatty Acids
5
Q
Degree of Saturation: Contain 1 double bond
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Monounsaturated Fatty Acids
6
Q
Degree of Saturation: Contain >1 double bond
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Polyunsaturated Fatty Acids
7
Q
Are associated with increased risk of cardiovascular diseases
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Trans- and saturated fatty acids
8
Q
Are thought to be protective
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Mono- and polyunsaturated fatty acids
9
Q
Geometric Isomerism of Unsaturated Fatty Acids
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Cis fatty acids
Trans fatty acids
10
Q
On the opposite side of the double bond
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Cis fatty acids
11
Q
On the same sides of double bonds
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Trans fatty acids
12
Q
Fluidity decreases with
A
Increasing chain length
Increasing saturation
13
Q
Essential Fatty Acids
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Linoleic Acid
Linolenic Acid
Arachidonic Acid
14
Q
Precursor of arachidonic acid 20:4 (5,8,11,14) which is essential in prostaglandin synthesis
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Linoleic Acid
15
Q
18:3 (9,12,15)
Deficiency results in decreased vision and altered learning vision
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Linolenic Acid
16
Q
Becomes essential if Linoleic Acid is deficient
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Arachidonic Acid
17
Q
Numbering starts from the last carbon atom
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Omega Fatty Acids
18
Q
Are correlated with a decreased risk of cardiovascular disease; Lowers thromboxane production; Reduced tendency of platelets to aggregate
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Omega-3 Fatty Acid
Omega-6 Fatty Acid
19
Q
Activation of Fatty Acids
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Must first be activated before being used in metabolism
Enzyme: fatty acyl-CoA synthetase
Co-factor: pantothenic acid
Energy used: 2 ATP equivalents
20
Q
Formation of Palmitate (16:0)
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Fatty Acid Synthesis
21
Q
Fatty Acid Synthesis: Where does it occur?
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In the cytosol
Major: liver and lactating mammary glands
Minor: adipose tissue
22
Q
Fatty Acid Synthesis: Substrates
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1 Acetyl CoA
7 Malonyl CoA
NADPH
ATP
23
Q
Fatty Acid Synthesis: Product
A
Palmitate only
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Fatty Acid Synthesis: Rate limiting step
Reaction: Acetyl CoA + ATP➡️Malonyl CoA
Enzyme: Acetyl CoA carboxylase
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Necessary co-factor for fatty acid synthesis
Biotin
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Fatty Acid Synthesis: Step 1
Synthesis of cytoplasmic Acetyl CoA
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Fatty Acid Synthesis: Step 2
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Acetyl CoA carboxylated to Malonyl CoA
Rate limiting step
Enzyme: Acetyl CoA carboxylase
Cofactor: biotin
Activators: insulin and citrate
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Fatty Acid Synthesis: Step 3
Assembly of Palmitate
| Enzyme: Fatty acid synthase
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Where does the cell primarily get the necessary NADPH?
Hexose monophosphate Pathway or
Pentose phosphate Pathway and
NADPH-dependent malate dehydrogenase (malic enzyme)
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Assembly is a sequence of steps
Condensation➡️
Reduction➡️
Dehydration➡️
Reduction
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Regulation of Lipogenesis
Activated by: Citrate, Insulin
| Inhibited by: Fatty acyl-CoA, Glucagon, Epinephrine
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Fate of Fatty Acids
Further elongation in smooth endoplasmic reticulum and mitochondria;
Desaturation in the ER through mixed function oxidases (cytochrome b5)
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Essential in the diet because they have double bonds that exceed the 9th carbon
Linoleic Acid
| Linolenic Acid
34
Esters of the trihydric alcohol Glycerol and fatty acids; Main storage forms of fatty acids; Coalesce within adipocytes to form oily droplets that are the major energy reserve of the body
Triacylglycerols (TAGs)
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Synthesis of TAGs: Where does it occur?
Liver
| Adipose tissue
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Synthesis of TAGs
Glycerol-3-phosphate + 3 fatty acyl CoA➡️triglyceride
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Sources of glycerol-3-phosphate
DHAP from glycolysis
| Phosphorylation of free glycerol
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DHAP from glycolysis
Enzyme: glycerol-3-phosphate dehydrogenase
| In liver and adipose tissue
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Phosphorylation of free glycerol
Enzyme: glycerol kinase
| In liver only
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What organs synthesize fatty acids?
Liver
| Adipose tissue
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Hydrolyzes TAGs to yielding free fatty acids and glycerol; Can only release fatty acids from carbon 1 and carbon 3 of the TAG in stored fat
Hormone-sensitive Lipase
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Bound to Albumin in blood for beta-oxidation
Free fatty acids
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Carbon backbone for gluconeogenesis
Glycerol
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Increase glucagon
| Increase cAMP➡️phosphorylation
Active Hormone-sensitive lipase
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Increase Insulin
| Decrease cAMP➡️dephosphorylation
Inactive Hormone-sensitive lipase
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Removal of Acetyl CoA fragments from ends of Fatty acids; Acetyl CoA can enter the citric acid cycle; generates NADH and FADH2 that can enter the ETC
Beta-oxidation of Fatty Acids
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Beta-oxidation of Fatty Acids: Where does it occur?
In the mitochondria of almost all cells but fatty acid activation occurs in the cytosol;
Exceptions are: neurons, RBC, testis, kidney medulla
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Beta-oxidation of Fatty Acids: Substrate
Palmitate
NAD+ + FAD
ATP
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Beta-oxidation of Fatty Acids: Products
8 Acetyl CoA
7 FADH2
7 NADH
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Beta-oxidation of Fatty Acids: Rate limiting step
Reaction: fatty acyl CoA + Carnitine➡️fatty acyl carnitine + CoA
Enzyme: carnithine acyltransferase
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Beta-oxidation of Fatty Acids reverses the process of fatty acid synthesis by
Oxidizing and releasing units of acetyl-CoA
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Oxidation of a fatty acid with an odd number of carbon atoms will yield
Acetyl CoA
| Propionyl-CoA
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Propionyl-CoA is converted to a TCA intermediate
Succinyl-CoA
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Propionyl-CoA carboxylase requires
Biotin
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Methylmalonyl-CoA mutase requires
Vit. B12
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Oxidize very long chains of fatty acids (C20, C22)
Peroxisomes
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Oxidation of unsaturated FAs require an additional enzyme
3,2 enoyl-CoA isomerase
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Energy Yield of Beta-oxidation
129 ATP
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Regulation of Beta-oxidation
Activated by: Glucagon
| Inhibited by: Malonyl-CoA, Insulin
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Alcohol leads to fat accumulation in the liver, called steatosis, which ultimately leads to cirrhosis; Alcohol dehydrogenase eats up NAD+ to reduce beta-oxidation in the liver
Fatty liver
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Can occur in newborn and manifest as hypoglycemia from impaired FA oxidation and muscle weakness from lipid accumulation
Carnitine Deficiency
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Affects only the liver resulting in reduced FA oxidation and ketogenesis with hypoglycemia
CPT I Deficiency
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Affects skeletal muscle and when severe the liver
CPT II Deficiency
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Decreased FA oxidation; During fasting, hypoglycemia can become profound due to lack of ATP to support gluconeogenesis; can manifest as Sudden Infant Death Syndrome
Medium-chain Fatty Acyl-CoA Dehydrogenase Deficiency (MCAD)
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Caused by eating unripe fruit of the akee tree , which contains hypoglycin, a toxin that inactivates medium and short-chain Acyl CoA dehydrogenase and leads to hypoglycemia
Jamaican Vomiting Sickness
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Rare neurologic disorder due to a defect that causes accumulation of Phytanic Acid which is found in plant foodstuff and blocks Beta-oxidation; Causes neurologic symptoms due to improper myelinization
Refsum's Disease
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Cerebrohepatorenal syndrome, which occurs in individuals with rare inherited absence of peroxisomes in all tissues; Characterized by liver dysfunction with jaundice, marked mental retardation, weakness, hypotonia, and craniofacial dysmorphism
Zellweger's Syndrome
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Defect in peroxisomal activation of VLCFA leads to accumulation of VLCFA in blood and tissues; Initial abnormalities are apathy and behavioral change; Visual loss, spasticity and ataxia follow
X-linked Adrenoleukodystrophy
69
Converts acetyl CoA to ketone bodies
Ketogenesis
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Ketogenesis: Where does it occur?
In liver mitochondria
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Ketogenesis: Substrate
Acetyl CoA
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Ketogenesis: Products
Ketone Bodies
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Ketogenesis: Rate limiting step
Reaction: Acetoacetyl CoA + Acetyl CoA➡️HMG-CoA
Enzyme: HMG CoA synthase
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6-Hydroxybutyrate➡️Acetoacetate➡️Acetyl-CoA
Ketogenolysis
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Can serve as fuel for extrahepatic tissues especially during fasting
Ketone Bodies
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In prolonged starvation and diabetic ketoacidosis, oxaloacetate is depleted for gluconeogenesis; In alcoholism, excess NADH shunts oxaloacetate to malate; Rate of Ketone Body Formation > Rate of Ketone Body Use
Ketoacidosis
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A steroid alcohol; Very hydrophobic compound; has a single hydroxyl group
Cholesterol
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Adrenal hormone not derived from cholesterol
Epinephrine
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De novo synthesis of Cholesterol
Cholesterol Synthesis
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Cholesterol Synthesis: Where does it occur?
Virtually all cells, in the cytosol and smooth endoplasmic reticulum
Majority: in the liver and intestines
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Cholesterol Synthesis: Substrate
Acetyl CoA
NADPH
ATP
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Cholesterol Synthesis: Product
Lanosterol➡️Cholesterol
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Cholesterol Synthesis: Rate limiting step
Reaction: HMG CoA➡️mevalonate
Enzyme: HMG CoA reductase
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Drugs used for the treatment of hypercholesterolemia, to reduce the risk for cardiovascular diseases
Statins
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Cholesterol Synthesis: Step 1
Biosynthesis of mevalonate
| Rate limiting step
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Cholesterol Synthesis: Step 2
Formation of isoprenoid units
| Isopentenyl diphosphate
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Cholesterol Synthesis: Step 3
Six isoprenoid units form isoprene
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Cholesterol Synthesis: Step 4
Formation of Lanosterol
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Cholesterol Synthesis: Step 5
Formation of Cholesterol
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An intermediate in the pathway
Farnesyl pyrophosphate
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How does the Acetyl CoA reach the cytosol for cholesterol biosynthesis?
Citrate shuttle
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High cholesterol limits the expression of HMG-CoA reductase gene by transcription factor (SREBP)
Production inhibition
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Insulin dephosphorylates and activates; Glucagon phosphorylates and inactivates
Enzyme phosphorylation
94
Elimination through conversion to bile salts then secretion into the bile
Cholesterol degradation
95
Synthesized in the liver from cholesterol
Bile Acids
96
Rate limiting enzyme of Bile Acids
Cholesterol-7-alpha-hydroxylase
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Regulation of Bile Acids
Activated by: Cholesterol
| Inhibited by: Bile Acids
98
Bile acid conjugated with either glycine or taurine; Primary means of excreting cholesterol; Emulsify lipids in the intestines
Bile salts
99
Excreted bile is reabsorbed in?
Terminal ileum
95% reabsorbed
5% excreted in feces = amount that liver must make
100
Steroid Hormone Synthesis: What is it for?
Precursor of ALL steroid hormones
Glucocorticoids (Cortisol)
Mineralocorticoids (Aldosterone)
Sex Hormones (Testosterone and Estradiol)
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Steroid Hormone Synthesis: Location
In the smooth endoplasmic reticulum of the adrenal cortex, ovaries, testes, placenta
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Steroid Hormone Synthesis: Substrate
Cholesterol
| Pregnenolone - "mother hormone" from which all other hormones are derived
103
Steroid Hormone Synthesis: Rate limiting step
Reaction: Cholesterol➡️Pregnenolone
Enzyme: Desmolase
Blocker: Aminogluthetimide
104
Lipid digestion begins in the
Stomach
105
Reach the capillaries of skeletal muscle and adipose tissue; Triglycerides broken to FA and glycerol via lipoprotein lipase
Chylomicrons
106
Directly enter adjacent muscle cells or adipocytes, or may be transported in blood bound to albumin
Free fatty acids
107
Converted to DHAP then enters glycolysis or gluconeogenesis
Glycerol
108
Manifests as steatorrhea (greasy stools); results in deficiency in fat-soluble vitamins and essential fatty acids
Lipid Malabsorption
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Causes of Lipid Malabsorption
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Liver Disease
Pancreatic Disease
Cholelithiasis
Shortened bowel
Intestinal mucosa defects
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Spherical macromolecule complexes composed of neutral lipid core surrounded by shell of amphipathic apoptoteins, phospholipid and nonesterified cholesterol
Plasma Lipoproteins
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Functions of Lipid Transport
1) Keep their component lipids soluble as they transport them in plasma
2) Provides an efficient mechanism for transporting their lipid contents to and from the tissues
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Represent the protein moiety of lipoproteins; Some are integral while others are free to transfer to other lipoproteins
Apolipoproteins or APO Proteins
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Transport dietary triglyceride and cholesterol from intestine to tissues
Chylomicrons
114
Apoproteins: Chylomicrons assembly + secretion; Secreted by epithelial cells
Apo B-48
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Apoproteins: Chylomicron, VLDL; Cofactor for lipoprotein lipase; Shuttled by HDLs
Apo C-II
116
Apoproteins: Chylomicron, VLDL; Mediates uptake of chylomicron remnant
Apo E
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Transport triglyceride from liver to tissues
VLDL
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Picks up Cholesterol from HDL to become LDL; Picked up by the liver
IDL
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Delivers cholesterol into cells
LDL
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Picks up cholesterol accumulating in blood vessels; Delivers cholesterol to liver and steroidogenic tissues via scavenger receptor; Shuttles apo C-II and apo E in blood
HDL
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Apoproteins: HDL; Activates LCAT
Apo A-I
122
Apoproteins: LDL, VLDL; Binds to LDL and VLDL receptors
Apo B-100
123
Deposition of Cholesterol and Cholesterol esters in the artery walls especially from oxidized LDL; Oxidized LDLs can cause endothelial damage
Atherosclerosis
124
Lipoprotein lipase deficiency; High VLDL and Chylomicron; Low LDL and HDL; Xanthomas and pancreatitis
Type I Familial Lipoprotein Lipase
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LDL receptors deficiency; High LDL; Xanthomas and Xanthelasmas with increased risk of atherosclerosis and coronary heart disease
Type II Familial Hypercholesterolemia
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Apo E deficiency; High remnants of VLDL and chylomicron with increased risk of atherosclerosis and coronary heart disease
Type III Familial Dysbetalipoproteinemia
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Increased VLDL production; Triad of: Coronary Artery Disease, DM type 2, Obesity
Type IV Familial Hypertriglyceridemia
128
Apo B-48 and 100 deficiency; No chylomicron, No VLDL/LDL; Intestinal malabsorption with accumulation of lipids in intestine and liver
Abetalipoproteinemia
129
Apo A1 deficiency; No HDL; Triglycerides and atherosclerosis
Familial a-lipoprotein Deficiency: Tangier's Disease
| Fisheye Disease
130
High HDL; Associated with benefits to health and longevity
Familial Hyperalphalipoproteinemia
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High LpA; Early atherosclerosis and Thrombosis
Familial Lipoprotein A Excess
132
Predominant lipids of cell membranes; Degraded by phospholipases
Phospholipids
133
Most abundant phospholipids; Represent a large proportion of the body's store of choline, important in nervous transmission, as acetylcholine and as a store of labile methyl groups
Phosphatidylcholine
134
Also found in cell membranes; plays a role in programmed cell death
Phosphatidylethanolamine (Cephalin) and Phosphatidylserine (for apoptosis)
135
Major lipid component of lung surfactant; Inadequate levels lead to Respiratory Distress Syndrome in the newborn
Dipalmitoylphosphatidylcholine (DPPC) or Dipalmitoyllecithin
136
Reservoir for arachidonic acid in the membranes; Source of 2nd messengers
Phosphatidylinositol
137
2 molecules of phosphatidic acid esterified through their phosphate groups to an additional molecule of glycerol; Found only in mitochondria and is essential for mitochondrial function; Antigenic
Cardiolipin
138
Part of the glycocalyx located on the outer layer of the cell membrane and functions in cell recognition and cell adhesion; Found in high concentrations in nervous tissues
Glycolipids
139
Sphingosine + Fatty Acid
Ceramide
140
Ceramide + Glucose or Galactose
Cerebroside
141
Ceramide + N-acetylneuramic acid
Ganglioside
142
Ceramide + Oligosaccharide
Globoside
143
Ceramide + Sulfated Galactose
Sulfatides
144
Only significant sphingophospholipid in humans where it is an important constituent of the myelin sheath of nerves
Sphingomyelin
145
Deficiency in phospholipids and sphingolipids from white matter resulting in increase CSF phospholipids
Demyelinating Diseases
146
Lipid storage diseases often manifested in childhood lipid synthesis is Normal; Lipid degradation in lysosomes is Abnormal
Sphingolipidoses
147
Hexosaminidase A Deficiency; Cherry red macula, MR and Hypotonia
Tay-Sach's Disease
148
Alpha-galactosidase Deficiency; X-linked recessive, Rash, Renal failure
Fabry's Disease
149
Ceramidase Deficiency; Triad of Skin rash, Hoarseness, Bone malformation
Farber's Disease
150
Arylsulfatase A Deficiency; Psychologic disturbance in adults due to demyelination
Metachromic Leukodystrophy
151
Beta-Galactosidase Deficiency; Mental Retardation
Krabbe's Disease
152
Beta-Glucosidase Deficiency; Hepatosplenomegaly + erosion of long bones
Gaucher's Disease
153
Sphingomyelinase Deficiency; Hepatosplenomegaly
Neimann-Pick Disease
154
Potent compounds that elicit a wide range of physiologic and pathologic responses
Eicosanoids
155
3 main kinds of Eicosanoids
Prostaglandin
Thromboxane
Leukotrienes
156
Eicosanoids: Dietary precursor
Linoleic Acid
157
Eicosanoids: Immediate precursor
Arachidonic Acid
158
Synthesized in platelets; Cause vasoconstriction and platelet aggregation
Thromboxane (TXA2)
159
Produced by blood vessel walls; Inhibitors of platelet aggregation
Prostacyclin (PGI2)
160
Mixture of leukotrienes C4, D4, and E4; Potent bronchoconstrictors
Slow-Reacting Substances of Anaphylaxis (SRS-A)
