Lipids Flashcards
Group of compounds insolublt to water, soluble in nonpolar solvents such as ether and chloroform
Lipids
Lipids are transported in the vlood via_____
Lipoproteins
Fats and waxes are classified under what type of lipids
Simple lipids
What classification of lipids include the ff: Phospholipids Glylipids Lipoproteins Sulfolipids Aminolipids
Complex lipids
What classification of lipids includes the ff: Fatty acids Glycerol Steroids Ketone bodies Hormones Fat-soluble vitamins and micronutrients
Precursor and derived lipids
Long chain of carboxylic acids
Fatty acids
Identify fatty acid
Predominant fatty acid in coconut oil
Lauric acid
Identify fatty acid
Structure is 12:0
Lauric acid
Identify fatty acid
End-product if mammalian FA synthesis
Palmitic acid
Identify fatty acid
Structure: 16:0
Palmitic acid
Identify fatty acid
Predominant FA in olive oil
Oleic acid
Identify fatty acid
Structure 18:1 (9)
Oleic acid
2 essential fatty acids
Linoleic acid 18: 2 (9,12)
Linolenic acid 18:3 (9,12,15)
Identify fatty acid
Precursor of prostaglandins, derived from linoleic acid
Arachidonic acid
Identify fatty acid
Structure: 20:4 (5,8,11,14)
Arachidonic acid
Dietary fatty acid
By-product of the saturation of fatty acid during hydrogenation or “hardening” of natural oils in the manufacture of margarine
Trans fatty acids
Dietary fatty acid
Increased risk for coronary heart disease, prostate CA and colon CA
Saturated fatty acids
Dietary fatty acid Has anti-inflammatory properties Supress cardiac arrhythmias, reduce serum TAGs, decrease the tendency for thrombosis, lower blood pressure Decreased risk for CHD Sudden cardiac death
Omega 3 FA
Dietary FA
Provide arachidonic acid which is an important precursor of prostaglandins and leukotrienes
Decreases risk for CHD
Omega 6 FA
Activated form of FA that participate in metabolic processes
Acyl CoA
Enzyme for activation of FA prior to its participation in metabolic processes
Fatty acyl CoA synthetase
Site of FA activation
Cytosol
Pathway for synthesis of FA, specifically palmitate
Lipogenesis
Site of lipogenesis
Liver, kidney brain, lung, mammary gland, adipose tissue
Cytosol
Immediate substrate for lipogenesis
Acetyl CoA
Product of Lipogenesis
Palmitoyl CoA
Rate-limiting step for lipogenesis
Acetyl CoA + HCO3- + ATP —> Malonyl CoA
Enzyme: Acetyl CoA carboxylasa
Mitochondrial acetyl CoA (from the oxidation of pyruvate) is transported to the cytosol using _____ shuttle
Citrate shuttle
Identify enzyme:
Citrate —> acetyl CoA + OAA
ATP citrate lyase
Identify enzyme
Acetyl CoA—> Malonyl CoA
Acetyl CoA carboxylase
In the elongation of FA to palmytoyl CoA,
____ is used as a primer
All subsequent carbon units are added via _____
Acetyl CoA
Malonyl CoA
Sequence of steps that are repeated seven times in elongation to palmitoyl CoA
Condensation—> Reduction —> Dehydration —> Reduction
______ is required as donor of reducing equivalents in the reduction reactions in the elongation to palmitoyl CoA
NADPH
3 substances/Pathways that serve as sources of NADPH in lipogenesis
Pentose phosphate pathway
Malic enzyme
Isocitrate dehydrogenase
Site of further elongation and desaturation of FA in lipogenesis
Smooth endoplasmic reticulum
Reaction in lipogenesis in which double bonds up to carbon 9 are introduced
Desaturation
Fatty acids are stored as _____
TAG
TAGs are synthesized by
Sequential addition of _______ to glycerol-3-phosphate
Removal of _______
Addition of _______
2 fatty acyl CoA
Phosphate
3rd fatty acyl CoA
2 sources of glycerol-3-phosphate
DHAP from glycolysis by enzyme GA3P DH (liver and adipose)
Phosphorylation of free glycerol by glycerol kinase (liver)
During fasting, stored fat is hydrolyzed to release _____
And 3 _____ by enzyme _______
Glycerol
FA
Hormone-Sensitive lipase
Hormone-sensitive lipase is activated by (increase/decrease) in the ff:
Insulin
Epinephrine
Cortisol
Decrease
Increase
Increase
During fat mobilization, FAs are remived from which carbons in TAG form
Carbon 1 and/or carbon 3
Phosphorylation/dephosphorylation
Insulin
Dephosphorylation
Phosphorylation/dephosphorylation
Glucagon
Phosphorylation
Phosphorylation/dephosphorylation
Epinephrine
Phosphorylation
Phosphorylation/dephosphorylation
TAG breakdown
Phosphorylation
Pathway for the removal of acetyl CoA freagments from the ends of FA, also yielding NADH and FADH2
Beta oxidation
Acetyl CoA produced from Beta oxidation enters what pathway
Citric acid cycle
NADH and FADH2 produced from beta oxidation can enter what pathway
ETC
Site of beta oxidation
Mitochondria
Site of fatty acid activation
Cytosol
Beta oxidation occurs in what tissues
Muscle and liver
Tissues that use fatty acids as energy source
Substrate for beta oxidation
Palmitate
3 products of beta oxidation
8 acetyl CoA
7 NADH
7 FADH2
Rate-limiting step for Beta oxidation and enzyme
Translocation of fatty acyl CoA from the cytosol to the mitochondria
Enzyme
Carnitine-palmitoyl transferase
Enzyme for the rate-limiting step of beta oxidation
Carnitine-palmitoyl transferase
Steps of beta oxidation:
_______ activates fatty acid
Fatty acyl synthetase
Steps of beta oxidation:
_______ attaches fatty acyl to carnitine in the outer mitochondrial membrane
Carnitine acyltransferase 1
Steps of beta oxidation:
_________ is shuttled through the inner membrane
Fatty acyl-carnitine
Steps of beta oxidation:
______ transfers fatty acyl group back to a CoA in the mitochondrial matrix
Carnitine acyltransferase 2
Sequence of steps repeated seven time in fatty acyl coa degradation
OHOT
Oxidation - hydration - oxidation - thiolysis
4 enzymes collectively known as fatty acid oxidase
Fatty acyl coa dehydrogenase
/\2 enol CoA hydratase
3 hydroxyacyl CoA dehydrogenase
Thiolase
Total ATP yield of palmitate
106
7 NADH (2.5 ATP each)
7 FADH2 (1.5 ATP each)
8 acetyl CoA (10 ATP each)
Activation (-2)
Oxidation of FA with odd number or carbon atoms will yield ____ and ____
Acetyl CoA and propionyl CoA
In oxidation of odd chain fatty acids, propionyl CoA is converted into ______, a TCA imtermediate
Succinyl CoA
2 sequential enzymes in oxidation if odd chain fatty acids
Propionyl CoA carboxylase
Methylmalonyl CoA mutase
In the oxidation of odd chain FA, propionyl CoA carboxylase requires this coenzyme
Biotin
In the oxidation of odd chain FA, methylmalonyl CoA mutase requires what co enzyme
Vitamin B 12
Organelle which serves as a site for oxidation of very long FA ( C20, C22)
Peroxisomes
Oxidation of very long chain FA requires this additional enzyme
3,2 enoyl CoA isomerase
Lipogenesis/Beta-oxidation
Rate-limiting enzyme is acetyl CoA
Lipogenesis
Lipogenesis/Beta-oxidation
Rate-limiting enzyme is carnitine-palmitoyl tranferase
Beta-oxidation
Lipogenesis/Beta-oxidation
Subcellular location is cytosol
Lipogenesis
Lipogenesis/Beta-oxidation
Located in mitochondria
Beta-oxidation
Lipogenesis/Beta-oxidation
Transport mechanism is citrate shuttle
Lipogenesis
Lipogenesis/Beta-oxidation
Transport mechanism is carnitine shuttle
Beta-oxidation
Lipogenesis/Beta-oxidation
Repetitive steps is condensation-reduction-dehydration-reduction
Lipogenesis
Lipogenesis/Beta-oxidation
Repetitive steps is oxidation-hydration-oxidation-thiolysis
Beta-oxidation
Lipogenesis/Beta-oxidation
Product is palmitate
Lipogenesis
Lipogenesis/Beta-oxidation Products include Acetyl CoA NADH FADH2
Beta-oxidation
Lipogenesis/Beta-oxidation
Activated by citrate
Lipogenesis
Lipogenesis/Beta-oxidation
Inhibited by long chain fatty acids
Lipogenesis
Lipogenesis/Beta-oxidation
Inhibited by malonyl CoA
Beta oxidation
Lipogenesis/Beta-oxidation
Favored by high insulin
Lipogenesis
Lipogenesis/Beta-oxidation
Favored by high glucagon
Beta oxidation
Rare disease that results in ichthyosis (scaly dermatitis), hair loss, poor wound healing, as well as visual and neurologic abnormalities
Deficiency of essential fatty acids
Hypoglycemia due to impaired fatty acid oxidation
Lipid accumulation
Muscle weakness
Canitine deficiency
Affects primarily the liver
Reduced fatty acid oxidation leading to severe hypoglycemia, coma, and death
Carnitine-Palmitoyl Transferase Deficiency
Affects primarily cardiac and skeletal muscle
Cardiomyopathy
Muscle weakness with myoglobinemia after prolonged exercise
Carnitine-Palmitoyl Transferase II deficiency
Dse that leads to decreased oxidation of fatty acids with 6-10 carbons
Medium Chain Fatty Acyl CoA Dehydrogenase
(MCAD) Deficiency
Most common inborn error of fatty acid oxidation
Autosomal recessive
M/c in Northern Europeans
Medium chain fatty acyl coa dehydrogenase deficiency
Severe hypoglycemia
Accumulation of FA in urine
Can manifest as Sudden Infant Death Syndrome
Medium Chain Fatty Acyl CoA Dehydrogenase Deficiency
Treatment for MCAD Deficiency
IV glucose in acute episodes
Avoidance of fasting
Dse caused by eating unripe fruit of the akee tree
Jamaican Vomiting Sickness
Dse characterized by toxin hypoglycin which inactivates medium- and short- chain acyl CoA dehydrogenase, inhibiting beta oxidatiom and causing hypoglycemia
Jamaican vomiting sickness
Dse characterized by deficiency of phytanoyl-CoA hydroxylase, leading to accumulation of phytanic acid
Refsum dse
In refsum dse, there is deficiency of ______ leading to accumulation of _______
Phytanoyl CoA hydroxylase
Phytanic acid
Peripheral neuropathy and ataxia, retinitis pigmentosa, abnormalities of skin and bone
Refsum dse
Tx for Refsum dse
Diet low in phytanic acid
Avoidance of dairy products, ruminant fat, and meat
Cerebrohepatorenal syndrome
Inherited absence if peroxisomes in all tissues leading to marked accumulation of very long chain, saturated, unbranched fatty acids in liver, and CNS
Zelkweger syndrome
Liver dysfunction with jaundice Marked mental retardation Weakness Hypotonia Craniofacial dysmorphism (high forehead, shallow orbits, hypertelorism, high arched palate, abnormal helices or ears, retrognathia) Early death
Zellweger syndrome
Inability to transport VLCFAs across peroxisomal membrane leading to accumulation in the brain, adrenals, testes
Adrenoleukodystrophy (ALD)
Neurodegeneration (initial apathy and behavioral change, followed by visual loss, spasticity, ataxia)
Adrenocortical insufficiency
Hypogonadism
Adrenoleukodystrophy (ALD)
Tx for adrenoleukodystrophy
Adrenal hormone replacement therapy
Hematopoietic stem cell transplantation
Diet therapy to decrease endogenous synthesis of VLCFAs
Synthesis of ketone bodies that serve as alternative fuel for peripheral tissues
Ketogenesis
Subcellular site for ketogenesis
Mitchondria of liver cells
Substrate for ketogenesis
Acetyl CoA
3 products od ketogenesis
Acetoacetate
Beta Hydroxybutyrate
Acetone
Rate-limiting step for ketogenesis
Acetoacetyl CoA + Acetyl CoA —> HMG CoA
Enzyme: HMG CoA Synthase
Ketone bodies produced in ketogenesis get converted into ______ in extrahepatic tissues, which enters the TCA
Acetyl CoA
Pathway in which ketone bodies are oxidized primarily in the mitochondria of extrahepatic tissues
Ketolysis
Site of ketolysis
Mitochondria of extrahepatic tissues: Skeletal and heart muscle Kidney Intestines Brain
T/F
The liver uses ketone bodies as fuel
F
It lacks the enzyme succinyl CoA-acetoacetate-CoA transferase (thiophorase)
Enzyme lacking in liver, rendering it incapable of using ketone bodies as source of fuel
Thiophorase (succinyl CoA-acetoacetate CoA transferase)
In prolonged starvation and diabetic ketoacidosis, OAA is depleted for what pathway
Gluconeogenesis
In alcoholism, excess NADH shunts OAA to_______
Malate
Identify the dse:
Severe metabolic acidosis Dehydration Potassium depletion Fruity odor of breath Decreased sensorium, possibly coma
Diabetic ketoacidosis
T/F
In DKA dx, the sodium nitroprusside reaction measures acetone, acetoacetate, and hydroxybutyrate
F, NOT hydroxybutyrate
Cholesterol is stored as _________
Cholesteryl esters
Adults normally synthesize _ gram of cholesterol and consume about ___gram per day
1g
0.3 g
Cholesterol structure has how many carbons
27
Cholesterol structure consists of a steroid nucleus composed of
Four hydrocarbon rings
In cholesterol structue, an eight-carbon brached hydrocarbon chain is attached to which carbon
Carbon 17 of D ring
In cholesterol structure, OH group is attached to _____
Carbon 3 of A ring
In cholesterol structure, double bond is located between which carbons
Carbon 5 and 6 of the B ring
Enzyme that converts cholesterol into bile acids
7a-hydroxylase
2 primary bile acids
Cholic acid
Chenodeoxycholic acid
2 secodary bile acids
Deoxycholic acid
Lithocholic acid
Bile salts are conjugated to _____ and ______
Taurine
Glycine
Enzyme that facilitates conversion of cholesterol to adrenal hormones and sex hormones
Desmolase
Cholesterol -> pregnennolone
Substrate for cholesterol synthesis
Acetyl CoA
Subcellular site of cholesterol synthesis
Cytosol and endoplasmic reticulum
Tissue site if cholesterol synthesis
Virtually all tissues
Most important: liver, intestine, adrenal cortex, ovaries, testes, placenta
Rate-limiting step for cholesterol synthesis
Hydroxymethylglutaryl CoA (HMG CoA) —> mevalonate Enzyme: HMG CoA reductase
Rate-limiting enzyme for cholesterol synthesis
HMG CoA reductase
Co factor of HMG CoA reductase in cholesterol synthesis
NADPH
Sequence of cholesterol synthesis:
Acetyl CoA to _____
HMG CoA
Sequence of cholesterol synthesis:
HMG CoA to _______
Mevalonate
Sequence of cholesterol synthesis:
Mevalonate to _________, with loss of CO2
Isoprenyl pyrophosphates
Sequence of cholesterol synthesis:
Isoprenyl pyroohosphate to ________
Squalene
Sequence of cholesterol synthesis:
Squalene to ______
Lanosterol
Sequence of cholesterol synthesis:
Lanosterol to _______
Cholesterol
Competitive inhibitor of HMG CoA reductase
Statins
Regulation of cholesterol synthesis:
Cholesterol and metabolites repress transciptoom HMG CoA reductase via activation of _________ transcription factor
SREBP (Sterol Regulatory Element-Binding Protein)
HMG CoA reductase is activated by phosphorylation/dephosphorylation
Dephosphorylation
HMG CoA reductase is inactivated by phosphorylation/dephosphorylation
Phosphorylation
HMG CoA reductase is increased/decreased by
Insulin
Increased
HMG CoA reductase is increased/decreased by
T3 T4
Increased
HMG CoA reductase is increased/decreased by
Glucagon
Decreased
HMG CoA reductase is increased/decreased by
Glucocorticoids
Decreased
T/F
Cholesterol ring cannot be metabolized in humans
T
Intact sterol nucleus is eliminated through conversion to ____________ which are eliminated in feces
Bile acids and bile salts
Intact sterol nucleus is eliminated through secretion of cholesterol in bile, which is transported to the intestines, where bacteria may convert it to _______
Coprostanol or cholestanol
Dysmorphic facial features Microcephaly Mental retardation Congenital heart disease Stillbirth
Deficient 7-dehydrocholesterol reductase
Smith Lemli Opitz Syndrome
Enzyme deficiency in Smith Lemli Opitz Syndrome
7-dehydrocholesterol reductase
Results when more cholesterol enters the bile than can be solubilized by the bile salts and phosphatidyl choline present
Cholelithiasis
Congenital adrenal hyperplasia can result from deficiency in either 2 of these enzymes
21 a hydroxylase deficiency (most common)
11B1 hydroxylase deficiency
What enzyme deficiency
Minelarocorticoids and glucocorticoids are absent
Overproduction of androgens leading to masculinization in females and early virilization in males
21 a hydroxylase deficiency (CAH)
What enzyme deficiency
Decreased serum cortisol, aldosterone, corticosterone
Increased deoxycoticosterone —> fluid retention (low renin hypertension)
Overproduction of androgens —> masculinization and virilization
11 B1 Hydroxylase (CAH)
Identify dse
Autoimmune destruction of the adrenal cortex which leads to adrenocortical insufficiency
Addison Dse
Precipitateed by Infection Trauma Surgery Vomiting Diarrhea Noncompliance to replacement steroids
Addisonian crisis
Hyperpigmentation in Addison Dse is due to excess _____ stimulating melanocytes to produce melanin
ACTH
Spherical macromolecular complexes of lipids and proteins are called ____
Apolipoproteins
Core of plasma lipoprotein is composed of
Neutral lipids
Shell of plasma lipoprotein is made of _______
Amphiphatic apolipoproteins, phospholipid, and free fatty acids
Keeps lipids soluble in plama and provides an efficient transport mechanism for lipids to and from various tissues
Plasma lipoproteins
Organ source of chylomicrons
Intestine
Identify lipoprotein
Largest diameter
Lowest density
Highest TAG content
Chylomicron
Protein and lipid % of chylomicron
1%
99%
Identify lipoprotein
7-10% protein
90-93% lipid
VLDL
Source of VLDL
Liver (like HDL)
Identify lipoprotein
Highest cholesterol content
LDL
Identify lipoprotein
Highest protein content
HDL
Source of ILDL
VLDL
Source of LDL
VLDL
2 Organ sources of HDL
Liver
Intestine
Free fatty acids are transported in the plasma bound to ______, woth low levels during the well-fed state, but with subsequent rise in the fasted state
Albumin
Free fatty acids increase/decrease
Fasted state
Increase
Free fatty acids increase/decrease
Well-fed state
Decrease
Identify apoprotein
Cofactor of lecithin:cholesterol acyltransferase
Apo A 1
Identify apoprotein
Found mainly in HDL
Apo A 1
Identify apoprotein
Main apoprotein
Mediates secretion of VLDL
Also found in VLDL, LDL
Apo B 100
Identify apoprotein
Mediates secretion of chylomicron
Apo B 48
Identify apoprotein
Cofactor of lipoprotein lipase
Apo C II
Identify apoprotein
Found in HDL, VLDL, chylomicrons
APO CII
Identify apoprotein
Mediates uptake of chylomicron remnants and IDLs
Apo E
Identify apoprotein
Found in chylomicron and ILDL
Apo E
Oxidized form of this lipoprotein cause endothelial damage which predisposes to atherosclerosis
LDL
Identify type of hyperlipoproteinemia
Familial lipoprotein lipase deficiency
Type I
Identify type of hyperlipoproteinemia
Deficiency of APO CII
Type I
Identify type of hyperlipoproteinemia High TAG low LDL Low HDL No increase risk of coronary disease
Type 1
T/F Type I hyperlipoproteinemia does not increase risk for coronary disease
T
Identify type of hyperlipoproteinemia
Defective LDL receptor
Type IIa
Identify type of hyperlipoproteinemia
Familiar hypercholesterolemia
Type IIa
Identify type of hyperlipoproteinemia
High LDL and cholesterol
Atherosclerosis and coronary disease
Type IIa
Identify type of hyperlipoproteinemia
Familial hyperlipoproteinemia
Type III
Identify type of hyperlipoproteinemia
Abnormal Apo E
Type III
Identify type of hyperlipoproteinemia
Hypercholesterolemia
Xanthomas
Atherosclerosis
Type III
Identify type of hyperlipoproteinemia
Familial triacylglycerolemia
Type IV
Identify type of hyperlipoproteinemia
Overproduction of VLDL
Type IV
Identify type of hyperlipoproteinemia
High VLDL and cholesterol
Subnormal LDL and HDL
Associated with CAD, DM Type 2, obesity, alcoholism
Type IV
Identify type of hyperlipoproteinemia Elevated lipoprotein (a), which is nearly identical to LDL
Familial lipoprotein (a) excess
Identify type of hyperlipoproteinemia
Atherosclerosis
Thrombosis due to inhibition of fibrinolysis
Familial lipoprotein (a) excess
Identify type of hyperlipoproteinemia
High HDL
Familial hyperalphalipoproteinemia
Identify type of hyperlipoproteinemia
Rare
Beneficial to health and longevity
Familial hyperalphalipoproteinemia (high HDL)
Identify type of hypolipoproteinemia
Defect in the loading of Apo B with lipid
No chylomicrons or VLDL
Abetalipoproteinemia
Identify type of hypolipoproteinemia
Low TAG
Accumulation of TAG in liver and intestines
Treated with large volumes of fat-soluble vitamins, particularly vitamin E
Abetalipoproteinemia
Identify type of hypolipoproteinemia
Low or near absence of HDL
Familial alpha lipoprotein deficiency
Tangier disease
Fish eye disease
Apo A1 deficinecies
Identify type of hypolipoproteinemia
High TAG
Absent HDL
Familial alpha lipoprotein deficiency
Tangier disease
Fish eye disease
Apo A1 deficinecies
Chylomicron metabolism
______ cells secrete nascent TAG-rich chylomicrons produced primarily from dietary (exogenous) lipids
Intestinal mucosal cells
Chylomicron metabolism
Apo ___ and Apo ___ are transferred from HDL to the nascent chylomicron
Apo CII and Apo E
Chylomicron metabolism
Extracellular _____, activated by APO CII, degrades TAG in chylomicron
Lipoprotein lipase
Chylomicron metabolism
Degradation of TAG by lipoprotein lipase yields _____ and _____
Free FA and Glycerol
Chylomicron metabolism
Apo ____ is returned to HDL
Apo CII
CE-rich chylomicron remnant bind through Apo ___ to specific receptors in the liver where they are endocytosed
APO E
VLDL metabolism
Liver secretes nascent, endogenously synthesized , TAG rich ______ particles
VLDL
VLDL metabolism
Apo C II and Apo E are transferred from ____ to nascent VLDL
HDL
VLDL metabolism
Extracellular lipoprotein lipase , activated by Apo ____, degrades TAG in VLDL
Apo CII
VLDL metabolism
Apo ___ and Apo ___ are returned to HDL
Apo C II and Apo E
VLDL metabolism
____ binds to specific receptors on extrahepatic tissues and on the liver, where they are endocytosed
LDL
