lipids Flashcards
lipids
composed of mostly of C-H bonds
- provide rich source of energy
- efficient way to store excess calories
integral part of cell membranes
- structural role
precursors for steroid hormones
lipids aren’t water soluble
- must form complexes with proteins to stay/travel in solution (lipoproteins )
- do not contribute to osmolality
clinically important lipids
- Sterol Derivatives
- cholesterol & cholesterol esters
- steroid hormones
- bile acids
- vitamin D
2.Fatty acids
- Glycerol Esters
- Triglycerides
- Phospholipids - Sphingosine Deravatives
- Terpenes ( Vitamin A,E,K)
Sterol Derivatives - Cholesterol
unsaturated steroid alcohol containing four rings
Amphipathic - contains both hydrophilic & hydrophobic parts
-the -OH group in the A-ring is hydrophilic
Found on the surface of lipid layers
- polar -OH group on A-ring faces outward ( away from lipid layer)
- the four rings & side chain tail are buried in the membrane
Cholesterol can be freee or esterified with fatty acid
- 70% exist as cholesteryl esters
ester=alcohol+ acid
cholesterol+fatty acid= cholesteryl ester
no polar groups on cholesteryl esters=hydrphobic
- therefore , not found on the surface of lipid layer
- located on the centre if intracellular lipid droplets
cholesterol synthesis - animals & plants
synthesized almost exclusively by animals
plants contain sterols called phytosterols
- similar structure to cholesterol
- known to lower total cholesterol & LDL-C in plasma
- known to raise HDL-C in plasma
cholesterol synthesis
synthesized in most tissued in the body ( particularly the liver)
synthesized from Acteyl-CoA
- >25enzymes involved
cholesterol synthesized in body= endogenous
cholesterol obtained from diet = exogenous
the body can synthesize all cholesterol it needs
precursor of bile salts, hormones & vitamin D
sterol derivatives- steroid hormones
include: testosterone, estrione, estradiol, estriol, progesterone, cortisol, corticosterone & aldosterone
female steroid hormones are produced in the ovaries & adrenal cortex
- Estrogens ex.estradoil
Male steroid hormones are produced in the testes & adrenal cortex
-Androgens ex.testosterone
Adrenal cortex hormones are used for mineral & water balance, CHO levels, liberation of fat from body storage & in response to inflammation, infection & allergies
sterol derivatives - bile acids & salts
bile contains 4 bile acids
- the most abundant is cholic acid
derived frim cholesterol
- of the cholesterol is catabolized into bile acids each day
bile is produced in the liver & stored in the gallbladder
released to small intestine during digestion
act as detergents to emulsify triglycerides in to the intestine to aid digestion
-eventually bile acids are reabsorbed & go back to the gallbladder
Sterol derivatives- vitamin D
fat soluble vitamin
natural sources include : fish, egg yolk
- milk, juice, cheese, yogurt can be fortified with vitamin D
involved in the absorption of calcium from the intestine
metabolizes calcium from bones
low vitamin D causes rickets
- poorly formed & easily broken bones
fatty acids chain lengths
linear chains C-H bonds ending with carboxyl group (-COOH)
- even #of carbon atoms
only a small amount exists in the free form ( bound to albumin)
most are found as constituent of triglycerides or phospholipids
can be classified by length as : short chain ( 4-6 carbon atoms ) medium chain (8-12) long chain (12-18) - most in our diet very long chain ( >20 carbon atoms )
fatty acids C=C bonds
can be classified by the number of C=C bonds :
saturated ( no double bonds)
monounsaturated (one double bond )
polyunsaturated ( 2 or more double bonds)
unsaturated fatty acids can be classified based on the position of the hydrogen atoms in relation to the C=C
- cis unsaturated fatty acids - both H atoms on the same side of C=C
- trans fatty acids-H atoms on opposite sides of C=C
Trans fatty acids
not commonly found in nature
present in diet die to chemical hydrogenation treatment during food processing
consumption of fatty acids increases the risk of coronary heart disease ( CHD)
- increases LDL ( bad cholesterol ) & decreases HDL ( good cholesterol)
polyunsaturated fatty acids
important in the structure & function of most biological membranes
some are beneficial in lowering the risk of cardiovascular disease (omega -3)
classified as:
omega -3 ( ex. linoleic acid)
omega -6 (ex. linolenic acid)
omega -9
fatty acid synthesis
most are synthesized by the body from carbohydrate precursors
exceptions:
linoleic & linolenic acids- essential fatty acids
- found in plants & must be obtained from the diet
- important for growth , maintenance & functioning of physiological processes
fatty acid catabolism
catabolism in the mitochondria to produced energy by a series of reactions known as ß-oxidation
fatty acids are converted tp Acetyl-CoA
Ketone formation
- when carbohydrate metabolism is impaired (ex. diabetes mellitus) , formation of acetyl-CoA is increased
- this results in the formation of excess ketone bodies
- acetone, acetoacetic acid, ß-hydroxybutyric acid
- the condition of ketosis develops from the excessive production of acetyl-CoA ( & therefore excess ketones) to obtain necessary energy from fats when there is a deficiency of carbohydrates
Glycerol Esters- Triglycerides
3 fatty acid molecules attached to a glycerol molecule by ester bonds
triglycerides containing saturated fatty acids tend to be solid at rook temp ( those from animal source)
Triglycerides continuing cis unsaturated fatty acids tend to form oils at room temp ( plant source )
no polar groups, so very hydrophobic & water insoluble
plays important role of tissue storage of lipids
90% of dietary fat
after absorption in the intestine, triglycerides are combined with cholesterol & apolipoprotein to form chylomicra which enters the blood
increased chylomicra in the blood gives the serum /plasma a milky appearance ( fasting specimen required)
glycerol esters - phospholipids
contain 2 fatty acids on the glycerol backbone with a phospholipid head group attached the 3rd carbon
- choline, phosphates, glycerol, serine , etc.
- hydrophilic
most common phospholipid is phosphatidylcholine or lecithin*
- found in lipoproteins & in cell membranes
Cephalins* involved in blood coagulation
Amphipathic
contain hydrophobic fatty acid C-H chains
- faces inward away form water group
hydrophilic head group
- faces outwards toward the aqueous environment
synthesized in all organs of the body especially liver q
Sphingosine Derivatives
Sphingolipids are all derived from the amino alcohol -sphingosine
major lipids of cell membranes & CNS
- Sphingomyelin * found in myelin sheath nerve cells
- Gangliosides * abundant in membranes of the grey matter of the brain
- Glycosphingolipids * role in cellular interactions & blood typing
important lipid points
synthesized in the liver or intestine
not readily soluble in blood
- need to be transported by macromolecular complexes called lipoproteins
lipoproteins
spherical macromolecules composed of lipids & proteins
non polar core ( hydrophobic & neutral)
- triglycerides
- cholesteryl esters
surface
- phospholipids ( polar head)
- free cholesterol ( has polar -OH group)
- apolipoproteins ( proteins that bind to fats fro transport & maintain structural integrity of the lipoprotein complex)
Structure of lipoproteins
main role of lipoproteins is delivery of fuel for peripheral cells
core represents the cargo that is being transported
size of lipoprotein depends on the core neutral lipid content
larger lipoprotein molecules contain more triglyceride & cholesteryl esters.
- also more lipid relative to protein
- therefore, lighter in density
Apolipoproteins
major protein component of lipoproteins ( primarily located on surface )
function : modulate the activity of enzymes that act on lipoproteins maintain structural integrity of the lipoprotein complex
Apo A- I is the major protein in HDL
Apo B-48 is the major protein in Chylomicra
Apo-B-100 is the major protein in LDL & VLDL
Apo C,E and (a) also exist
Classification of lipoproteins
- Chylomicrons
- very low density lipoprotein ( VLDL)
- Intermediate - density lipoprotein (IDL)
- low -density lipoprotein ( LDL)
- high density lipoprotein (HDL)
- Lipoprotein (a) [Lp(a)]
higher the % of protein = higher density
generally the larger lipoprotein contain more lipids, triglycerides & cholesteryl esters with less protein & are therefore lighter
Chylomicrons
produced by the intestine
largest & least dense of the lipoprotein particles
major carrier of exogenous triglycerides ( dietary lipids) to body cells***
contains app B-48
2-6 hours after a meal , most triglycerides are transported on chylomicrons
float to the top of stored plasma & give a “creamy layer”
causes of lipemia - milky appearance
Very low density lipoproteins ( VLDLs)
produced primarily by shelver
major carrier of endogenous triglycerides from the liver to the body cells ***
contains Apo B -100( mainly), Apo E & Apo Cs
in the fasting state most triglycerides are present in as VLDL
excess dietary intake of carbohydrates, saturated fatty acids & trans fatty acids increases hepatic synthesis of triglycerides, which increases VLDL production
intermediate density lipoproteins (IDL)
also referred to as VLDL remnants
only exists for a short period if time during conversion of VLDL to LDL
won’t see in large quantities
- process of conversion id efficient & doesn’t allow accumulation
exception :
Type 3 hyperlipoproteinemia ( dysbetalipoproteinemia or broad beta disease )
- inborn error of metabolism due to abnormal form of Apo E
-clearance of IDL is delayed & elevated levels will be found in plasma
- at significant risk for peripheral vascular disease (PVD) & coronary artery disease (CAD)
low density lipoproteins ( LDLs) “ bad”
contain Apo B -100
- more cholesterol rich than other apo-B containing lipoprotein
formed by lipolysis of VLDL
major carrier of cholesterol from liver to the cells ***
because of their small size they can infiltrate the extracellular space of the vessel walls
- here they become oxidized & taken up by macrophages
- macrophages that have taken up too much lipid fill with lipid droplets & turn into foam cells
- the foam cells form fatty streaks - a precursor of atherosclerotic plaques
High density lipoproteins
produced by the liver & intestine
smallest & most dense lipoprotein
contains Apo A-I
removes excess cholesterol from the cells to the liver
- reverse cholesterol transport
increased HDL decrease risk of coronary heart disease
we want >0.9mmol/L
Lipoprotein (a)
LDL- like particles
one molecule of apo (a) linked to app B-100
elevated levels are known to increase risk of premature CHD & stroke
currently not often used in clinical practice
- measurement is difficult
- limited therapies available to reduce levels
Lipoprotein X
Abnormal lipoprotein
present in patients with :
billiard cirrhosis or cholestasis ( liver disease or bile impairment)
mutation sin the lecithin - cholesterol acyltransferase ( LCAT) enzyme
typically included in the LDL -c measurement
lipemic sample
lipemic sample - microcentrifuge
pg. 135 lipid reference ranges
