Lipid Metabolism Flashcards
Lipids is stored as addipose tissue for what?
4
- insulation
- support vital organs
- generate heat
- stored as energy reserve
Lipid ingestion goes through digestion and absoprtion and goes where?
lipids in blood as lipoproteins
Lipids in blood as lipoproteins are then used as what?
5
- excreted in the feces
- stored as an energy reserve
- synthesized from carbohydrates and proteins
- Oxidize for energy
- Convert to brain and nerve tissue
What are lipids?
What are the three different kinds?
chemical substances composed of long-chain fatty acids
Triglycerides
Phospholipids
Cholesterol
What lipid is used in energy metabolism?
Triglycerides
Phospholipids are important structural components of what?
4
Important structural components of
- lipoproteins,
- blood clotting components,
- myelin sheath and
- cell membranes
Funcitons of cholesterol?
3
Where is it obtained and synthesized?
Elevated levels are implicated in the development of what?
- Precursor of steroid hormones
- Necessary for cell membrane synthesis
- Metabolic precursor of bile acids
Obtained from the diet and synthesized in the liver and intestinal mucosa
Elevated levels are implicated in the development of atherosclerosis
Where are chylomicrons synthesized?
They are involved in the transport of what? 2
Largest of the protein molecules
Synthesized in the wall of the small intestine
Involved in the transport of dietary triglycerides (TG) and cholesterol that have been absorbed from the GI tract
Where does cholesterol transfer TG to? 2
Remnant particles, which contain cholesterol, are then taken up by what?
What does this cholesterol do then?
2
Transfer their TG to the cells of adipose and skeletal muscle tissue
the liver
The cholesterol is used in the synthesis of VLDL or is excreted in the bile
The rate limiting step in cholesterol synthesis involves the enzyme what?
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
Cholesterol and other lipids are transported in the circulation as a component of what?
lipoproteins
What are the funtions of lipoproteins?
cholesterol and triglyceride are insoluble in plasma, they are encapsulated by special fat-carrying proteins called lipoproteins
Five types of Lipoproteins (listed in order of % of TG)
What is the main carrier of cholesterol?
- Chylomicrons
- Very low density lipoprotein (VLDL)
- Intermediate density lipoprotein (IDL)
- Low density lipoprotein (LDL)
The main carrier of cholesterol*** - High density lipoprotein (HDL)
The cholesterol level in blood is determined by a combination of factors and/or secondary causes?
10
- Genetics
- Age
- Dietary intake of saturated fat and cholesterol
- Sedentary lifestyle
- Poorly controlled DM
- Hypothyroidism
- Nephrotic syndrome
- Obstructive liver disease
- Alcoholism
- Drug therapy (cyclosporine, glucocorticoids)
The liver synthesizes and releases what lipids? 2
VLDL and HDL
VLDL’s contain large amounts of what?
Provide the primary pathway for transport of what?
The TG content of VLDL particles initially is___ and _______ progressively as a result of enzyme activity in the bloodstream
triglycerides
endogenous TG produced in the liver
high,
decreases
VLDL carry TG to what where they are removed? 2
What does this result in?
2
fat and muscle cells
- Resulting IDL fragments are enriched in cholesterol and taken to the liver and recycled to form VLDL….
- or converted to LDL in the vascular compartment
IDLs are the main source of LDL
What is considered bad cholesterol?
LDL
LDL is removed from the circulation by what?
2
- by LDL receptors (70%) on hepatocytes or
- by non-receptor mechanisms involving scavenger cells such as macrophages
the liver plays an extremely important role in LDL metabolism
What non-hepatic tissues also use the receptor-dependent pathway to obtain cholesterol needed for membrane and horomone synthesis?
4
- adrenal glands,
- smooth muscle cells,
- endothelial cells,
- lymphoid cells
The amount of LDL that is removed by the scavenger pathway is directly related to what?
The uptake of LDL by macrophages in the arterial wall can result in the accumulation of what? 3
to the plasma cholesterol level
- Insoluble cholesterol esters
- Formation of foam cells
- Development of atherosclerosis
* *more about this later
What is good cholesterol and where is it synthesized?
How does it participate in cholesterol transport?
Studies show what kind of relationship between HDL and the develpomennt of atherosclerosis?
Why? (three steps)
HDL, Synthesized in the liver
Participates in the reverse transport of cholesterol, that is, carrying cholesterol from the peripheral tissues back to the liver
inverse
- HDL facilitates the clearance of cholesterol from atheromatous plaques and
- transports it to the liver, where it may be
- excreted rather than used in the formation of VLDL
HDL is also believed to inhibit what?
What has been observed to increase HDL levels? 2
What has been observed to decrease levels of HDL? 2
cellular uptake of LDL
regular exercise and moderate alcohol consumption
Smoking and the metabolic syndrome
What is an Apoproteins (or Apolipoproteins)?
What are the major classes?
What do apoproteins control?
Research findings indicate that genetic defects in apoproteins are involved in what disease processes?
2
Two sites for apoprtein synthesis?
Each type of of lipoprotein consists of a large molecular complex of lipids combined with proteins called apoproteins
Six major classes (A B C D E H)
Apoproteins control the interactions and ultimate metabolic fate of the lipoproteins….regulate lipid transport and metabolism
hyperlipidemia and accelerated atherosclerosis
The small intestine and the liver
Atherosclerosis begins with what?
Chemical modification (particularly oxidation) of lipoproteins leads to what?
Begins with accumulation of lipoproteins (primarily LDL) within the inner layer of the arterial wall
a local inflammatory reaction involving macrophages, which ingest oxidized lipoproteins and form foam cells
Accumulation of foam cells contributes to the formation of what?
What do these progress to over time?
fatty lesions
fibrous plaques
Fissures may develop in a plaque, exposing the underlying tissue to what?
platelets
PLatelet adhesion, activation, and aggreggation lead to what?
thrombus formation, partially or completely occluding the vessel lumen
Ingested fat passes through the ____ and continues on to the _____ where it is then emulsified by ____?
stomach
duodenum
bile
- Long chain fatty acids are packages into ____ in the ___?
- These _____ are then taken up by mucosal cells and used in the synthesis of ____?
- Nascent (immature) chylomicrons enter the blood at the _____?
- How do immature chylomicrons become mature ones?
- Where are HDLs synthesized?
- LPL (lipoprotein lipase) is activated by _____, allowing triglycerides in the lipoprotein to be broken down
- The resultant free fatty acids and diglycerides are taken into what to be used how?
- How do chylomicrons become chylomicron remnants? What are these taken up by then?
What are these remnants used for then? - LDL is activated by ____, allowing ______ in the lipoprotein to be broken down
- VLDL then donates _____ to to ______ in the blood stream and becomes _____?
- When is IDL considered to become LDL?
- The LDL are then taken up by the tissues where they are what? 2
- micelles
small intestine - micelles
chylomicrons - thoracic duct
- HDLs donate apoproteins to the nascent chylomicrons yielding mature chylomicrons
- HDLs are synthesized primarily in the liver
- Apoprotein CII
- The resultant free fatty acids and diglycerides are taken into the adjacent adipose tissue cells (adipocytes) and either utilized or stored
- Chylomicrons then donate Apoprotein CII to HDL in the bloodstream and become chylomicron remnants. Taken up by the liver and used to synthesize nascent VLDL.
- Apoprotein CII
triglycerides - Apoprotein CII
HDL
LDL - As IDL become less dense through the loss of triglycerides, they are considered LDL
- stored or used as fuel
* 95% of the fat in food is digested and absorbed into adipose tissue
Lipoprotein is composed of what? 2
Apoprotein functions?
3
phospholipid + protein complex circulating in blood
- provide interface between lipids and aqueous environment
- regulate lipid transport
- regulate lipoprotein metabolism
Chylomicrons are involved in what kind of transport?
What do they carry from the gut to the liver? 3
VLDL is involved in what kind of transport?
What do they carry from the liver to the peripheral tissues? 3
What does HDL carry?
What does it have an inverse realtionship with?
LDL is the main carrier of what?
(from where to where?)
What is it linked to?
What does an elevation of LDL result from?
Exogenous transport pathway
Carry TG, dietary fat and cholesterol from the gut to the liver
Endogenous transport pathway
Main carrier of TG (also cholesterol and cholesterol esters) from the liver to peripheral tissues
Carries cholesterol from peripheral tissues back to liver
Inverse correlation with coronary heart disease risk
Main carrier of cholesterol from liver to peripheral tissues
Linked to coronary atherosclerosis
Elevation result from excess production or defective clearance and utilization of cholesterol
What makes a saturated fatty acid saturated? 2
What kind of foods does this encompass?
- Saturated fatty acids have single bonds between the carbon atoms
- The C atoms are full, or “saturated”
–Most animal fat (and coconut oil) is saturated
Whole milk, butter, cheese, eggs, egg yolk, fatty meats
Monosaturated FAs contain only one ____ bond.
What kind of foods does this encompass?
double
Example, oleic acid as found in olive oil
Polyunsaturated FAs contain what kind of bonds?
What kind of foods does this encompass?
two or more double bonds
Includes most vegetable fats
Vegetable oils like soybean, sunflower ,corn, safflower
Fish like tuna, salmon, herring
What is ketosis?
When does it occur?
Excess ketone bodies will decarboxylate into what?
Name two situaitons where this occurs?
result of the liver converting fat into fatty acids and ketone bodies (which can be used for energy as an alternative to glucose
Ketosis occurs when the rate of formation of ketones by the liver is greater than the ability of tissues to oxidize them
acetone
- Starvation
- When large amounts of fat are eaten in the absence of carbohydrate
Such as low carb diets
Health Risks Associated with Obesity
7
- Type 2 Diabetes (NIDDM)
- Cardiovascular Disease
a. Hypertension
b. Dyslipidemia (high total cholesterol, low HDL, high LDL, high triglycerides) - Sleep-Breathing Abnormalities
a. difficulty breathing
b. obstructive apnea - Gallstones
- Menstrual irregularity, difficulty getting pregnant
- Osteoarthritis
- Cancer (colon, endometrial, breast)
DYSLIPOPROTEINEMIA
Lipid disorders are classified as— (2)
Primary
secondary
DYSLIPOPROTEINEMIA Type 1 (3 clinical features) Type 2 (4 clinical features) Type 3 (2 clinical features) Type 111 (4 clinical features) Type 1V (1 clinical feature) Name the lipoprotein involved, affect on cholesterol and TG and name the clinical features?
Type 1 Lipo: chylomicrons Chol: N TG: ↑ Clin Feat: Pancreatitis, eruptive xanthomas, lipemia retinalis
Type 2 Lipo: LDL Chol: ↑ TG: N Clin Feat: Pancreatitis CAD, tendon xanthomas, arcus cornea
Type 3 Lipo: LDL + VLDL Chol: ↑ TG: ↑ Clin Feat: Pancreatitis, CAD
Type 111 Lipo: Remanant of VLDL and chylomicrons Chol: ↑ TG: ↑ Clin Feat: Pancreatitis, CAD, PVD, palmer and tuberous xanthomas
Type 1V Lipo: VLDL Chol: N TG: ↑ Clin Feat: Premature CAD
Causes of 2ry hyperlipdemia
10
1—extra hepatic obstruction 2 - 1ry biliary cirrhosis 3—DM 4—hypothyroidism 5—alcochol 6-Nephrotic syndrome 7-obesity 8-high dose thiazide diuretic 9—exogenous sex hormone 10--steroids
Familial hypercholesterolemia
is associated with what?
Its a genetic defect involving what and resulting in what?
What does this do to the LDL levels?
What disease does it cause?
Symtpom that 70% have by age of 30? (where is it located? 3)
Associated with high risk of premature CAD
Genetic defect in the LDL receptor gene resulting in either absent or defective LDL receptor activity
This increses LDL cholesterol by 2-3 folds
Causes premature CAD
Tendon xanthomas—on the backs of the hands, knuckles and the achilles tendon
Familial combined hyperlipidemia
is different from Familial hypercholesterolemia how?
What is common? 4
Tendon xanthomas DO NOT occur
- Obesity and
- insulin resistance are common
- Corneal arcus are present
- Xanthelasma are present
If a pt has Remanant particle disease what are they at a higher risk for? 2
What are the symtpoms?
2
What lab levels are markedly elevated? 2
Risk of premature CAD and PVD
Palmer xanthoma , tuberous and eruptive xanthomas
Cholesterol and TG are markedly elevated
Chylomicronemia syndrome
is characterized by what?
What will cholesterol levels look like?
It usually occurs in pts with what?
3
Characterized by massive hypertriglyceredemia
Cholesterol level may be normal
Usually occurs in pts with ---alcohol access ---DM ---anti retroviral therapy
Chylomicronemia syndrome presents how?
4
Presents with
- —eruptive xanthomas
- —hepatospleenomegaly
- –lipemia retinalis
- –↑risk of pancretitis—pts complain of intermittant abdominal pain
Total cholesterol is desribale at what level?
What is high?
less than 200
over 240
What is optiminal LDL levels?
What is high and very high?
below 100
over 160 and over 190
Risk factors for high cholesterol?
5
- Smoking
- Hypertension—140 / 90
- Family h/o premature CAD
- Age 45 in males—females 55
- HDL
MANAGEMENT for high cholesterol? 2
Drugs? 5
What do we have to rule out before we start to treat? 4
- Main indication of RX is prevention of vascular disease
- Diet
- - Goal for at least 6 months
Drugs
- HMG-Co A reductase inhibitors {statins}
- Fibrates
- Nicotinic acid
- Bile acid sequesterons
- Cholesterol absorption inhibitors
Exclude secondary causes—
- –glucose tolerance
- —TFT (thyroid ft)
- —U&E (urea and electrolytes)
- —LFT (liver ft)
What are the HMG-Co A reductase inhibitors {statins} drugs?
3
- -pravastatin
- -simvastatin
- -atorvastatin
What are the fibrate drugs?
2
- gemfibrocil
- -fenifibrate
What are the Bile acid sequesteron drugs?
2
- -cholestyramine
- –colestipol
Cholesterol absorption inhibitors
drugs?
2
- -ezetimibe
- -probucol
