Final Flashcards
Roles of lipids
●Energy Storage
●Cell Membranes
●Endocrine Signaling
Fatty Acid facts
●carboxylic acid and hydrocarbon tail (4-36 carbons)
●names end in -ate
●most abundant are unbranches and 12-20 carbon (even numbered)
●covalently bond to proteins to tether proteins to membranes
●amphipathic
Saturated Fatty Acids
●contains hydrogens
●Fully reduced methylene groups (CH2)
●generally used for energy storage because of high redox potential
●solid at room temp
Unsaturated Fatty Acids
●contains at least one C=C
●Monounsaturated fats: only one C=C
●Polyunsaturated fats: multiple C=C
●Polyunsaturated usually components of membrane
●naturally in cis configuration
●liquid at room temp
Chemical Reactions with Fatty Acids
●hydrogenation: unsaturated into saturated (presence of hydrogens to reduce double bond)
● accompanied by isomerization rxn (produces trans fat -> cause higher cholesterol levels and incidence of heart disease)
Fatty Acid Nomenclature
●first number= number of carbon atoms in chain (1st carbon is the carboxylic acid carbon)
●second number= number of double bonds
●exponent of delta= where the first C of the db is
●using omega= counting carbons from the end instead
Triacylglyercols
●the other lipid that functions as fuel storage
●3 fatty acids esterified to a glycerol (product of 3 water molecules as well)
●more energy than carbs during oxidation
●carbs for immediate energy
Saponification
●Ester hydrolysis of fat with lye (KOH or NaOH)
●Lye is alkaline mixture from wood ash
●hard water (Mg or Ca) causes formation of precipitate called soap scum
●micelles: hydrophilic head, hydrophobic tail -> reduce entropy (tails can attach to dirt and form circle where dirt is in the middle)
●glycerol separated out
Steroids
●non-saponifiable lipid
●include bile salts, cholesterol, and related compounds, and certain hormones
●exist alone or combined with FAs or carbohydrates
●four fused ring structure (three 6 carbon rings and 1 five carbon ring on the right)
Cholesterol
●OH at position 2
●most abundant steroid
●1/2 in lipid bilayer of cell membrane
●rest converted into cholic acid (used to form bile salts)
●precursor for sex hormones, adrenal hormones, and vitamin D
Lipid Transport
●nonpolar fats and cholesterols must be transported by lipoproteins through aqueous blood stream
●Lipoproteins are molecular complex made of a core of hydrophobic lipids surrounded by a shell of polar lipids and apolipoproteins
●vary by size an density of proteins present
Chylomicrons
●largest lipoprotein
●monolayer phospholipid membrane containing free cholesterol
●membrane derived from endomembrane system of intestinal epithelial cells
●interior contains large amounts of triacylglycerols and cholesterol esters
Cholesterol- Heart Health
●lipids less dense than proteins (low density lipoproteins (LDL) contain more lipids than proteins)
●LDLs are greasy and clump together -> causes build up on walls of blood vessel = heart disease
●high density lipoproteins (HDL) have more proteins, more soluble in water -> lower risk of heart disease
Triacylglycerol in metabolism
●stored in adipose tissues from dietary fats
●fats entering small intestine from stomach are insoluble and need emulsification by bile acids (secreted by bile duct and functions as detergent to promote micelle formation, transport triacylglycerols)
●cleaved by lipases to make free fatty acids and glycerol
●fatty acids pass through membrane on luminal side of intestinal epithelial cells
●remake glycerol and package into chylomicron
●chylomicron transport until endothelial cell
●lipase again and fatty acid into albumin
●fatty acids transport by albumin to adipose and muscles tissue (glycerol goes to liver through blood) (form albumin-fatty acid complexes)
●chylomicron remnants recycled and repackaged in liver once depleted of fatty acids
Steps of making chylomicron
●dietary triacylglycerols emulsified by bile acids
●lipase cleavage
●fatty acids synthesized into triacylglycerols
●packaged into chylomicrons
Lipid droplets
●storage vehicle for newly formed triacylglycerols from adipocytes
●surrounded by phospholipids monolayer containing perilipin (protein used to prevent fat degradation via enzymes)
Glucagon receptor Gas
●signaling initiates cascade causing fatty acid release to bloodstream
●PKA-> make fatty acid binding protein 4 (beta barrel)
●albumin with fatty acids to tissues
Cell membranes
●protect organisms from environment by hydrophobic barrier
●plasma membrane separate outside of cell form inside and has numerous proteins
●gives cell shape
●fluid mosaic (movement, level of fluidity)
●50% protein and 50% lipids by weight
●3 major types: glycerophospholipids, sphingolipids, cholesterol
Glycerophospholipids
●most abundant membrane lipids
●contain two fatty acids and a phosphate group attached glycerol backbone
●polar head added to phosphate group
●examples: phosphatidylcholine (N+), phosphatidylserine (NH3 and COO-), phosphatidylethanolamine (CH2N+H3), phosphatidylinositol (chair configuration with OHs)
●important source of fatty acids derived signaling molecules, which are released by phospholipase enzyme catalysis
●snake venom -> tissue damage by membrane breakdown and detergent effect of free fatty acids (formation of micelle that can interrupt bilayer and insert into membrane)
phosphatidylinositol
●PIP2
●broken down
●lipids in membrane meant to be broken down to make signaling molecules
●inner side of membrane
phosphatidylcholine
●found in exoplasmic or outer leaflet of membrane
●plays role in membrane-mediated cell signaling and enzyme activation
●increase membrane fluidity (more branching)
phosphatidylethanolamine
●aka cephalins
●found in brain tissues and nerves (in membrane)
●also have role in blood clotting (not in membrane)
●inner side of membrane
phosphatidylserine
●in inner leaflet of plasma membrane
●along with cholesterol, helps to form lipid rafts and microdomains in membrane (crucial for organizing and segregating membrane proteins)
Lipid Rafts
●protein aggregated in discrete patches as densely packed protein complexes
●contain large transmembrane proteins
●act as receptors for extracellular signaling
●receptor can’t move around much
●way less fluid part of membrane
●more cholesterol
Cholesterol in membrane
●25%-40% of lipids in plasma membrane
●27 carbons and 4 ring structure
●a lot is planar
●affects fluidity
●polarity provides stability
●precursor for steroid hormones and bile acids
●from mevalonate
●too much= heart disease
Sphingolipids
●from sphingosine (long chain amino alcohol synthesized from palmitate and serine, one fatty acid, and polar head group)
●examples: sphingomyelin (sphingophosolipid, phosphocholine head), cerebroside (sphingoglycolipid, glucose), gangliosides (sphingoglycolipid, GM1 glycan)
Cerebrosides
●important part of membrane of nerve and brain cells
●contain single sugar polar head group (galactose or glucose)
Gangliosides
●important role in cell recognition and membrane function
Triacylglycerols transportation
●dietary= chylomicrons
●synthesized in liver= exported in lipoproteins (VLDL particles)
●adipose tissue released as fatty acids by hormone signaling= albumin
Cholesterol derivative
●steroid hormone (ex: progesterone)
●bile acid (ex: glycocholate)
●efficient to make steroid hormones from cholesterol because it’s easier to just add groups onto something we have so much of
Steroid hormones
●ligands for nuclear receptor proteins, which mediate hormone signals by altering expression for specific genes
●endocrine
●half life of hours (time to travel throughout body)
●potent signaling molecules that have a critical role in: cell development, reproductive biology, organismal physiology
●two main groups: adrenocortical and sex hormones
●steroidogenesis generates cholesterol-derived hormones through action of cytochrome P450 monooxygenases (how almost every drug is broken down)
Cytochrome P450s
●class of heme-containing oxidoreductase enzymes that alter side groups on substrate molecules in reactions involving oxygen.
●enzymes metabolize majority of exogenous drugs consumed- main detoxers
●subtle difference in side groups of steroid hormones account for their distinct agonist or antagonist functions
Synthetic Hormones
●agonists mimic biological response of the hormone
●dihydrotestosterone: natural androgen agonist that promotes male reproductive development
●Nandrolone: potent synthetic androgen agonist, used by bodybuilders
●bicalutamide: nonsteroidal androgen antagonist used to treat prostate cancer
Steroid Hormones functions
●progesterone: menstruation, development of mammary tissue
●cortisol: liver metabolism, immune functions, adaptation to stress
●aldosterone: ion transport in kidneys, blood pressure regulation
●testosterone: development of male reproductive organs
●estrogen: development of female reproductive organs
Lipids in cell signaling
●example: eicosanoids
Eicosanoids
●group of signaling molecule derived from arachidonate (omege-6 FA) that is converted into regulatory molecules called eicosanoids
●immune-system signaling molecules and are released from membrane by phospholipase and modified by mitochondrial enzymes
●produced by cells at their site of action (paracrine)
●half lives of only few minutes
●four major classes: prostaglandins, prostacyclins, thromboxanes, leukotrienes
Prostaglandins
●discovered from compounds in human semen that regulate blood flow when injected into animals
●found in most tissues in both male and females
●primarily act on GPCRs
●also activate uterine contraction during birth, and stimulate inflammatory response (tissue swelling, pain, fever)
NSAIDs and Cell Signaling
●Gas activation
●Acetylsalicylate from willow tree (salix alba)
●used for aspirin
●Bayer chemist succeeded in creating first pure and shelf-stable formulation of acetylsalicyclic acid from salicyclic acid
●inhibitor of COX-1 and COX-2
●arachidonate to prostaglandin
Cox-1
●constitutively expressed in most tissues
●involved in producing prostaglandins that stimulate mucin secretion and protect stomach lining from low pH
●protect against stomach ulcers
Cox-2
●expression is induced by inflammatory signals
●responsible for producing prostaglandins that cause pain, swelling, and fever associated with inflammation
How does NSAIDS inhibit
●esterification at active-site on serine residue
●celebrex and vioxx only target Cox-2 to keep Cox-1 creating the stomach lining
Prostacyclins
●prevent platelets from sticking together (help prevent blood clotting)
●effective vasodilation via production of cAMP (Gas)
●increase blood flow (similar to epinephrine), makes sense that they use the same pathway
Thromboxanes
●regulate blood vessel constriction
Leukotrienes
●act as inflammatory mediators that also regulate smooth muscle contraction
