| Question |
Answer |
| 5 roles of lipids |
1)energy storage 2)components of biological membranes 3)messenger molecules 4)covalent protein modifications 5)building blocks for hormones |
| 5 types of lipids |
1)fatty acids 2)neutral glycerides 3)phospholipids 4)sphingolipids 5)cholesterol and derivatives |
| fatty acid characteristics |
even numbered, 12-24 carbons, un/saturated, all double bonds in cis configuration, at least 3 carbons between double bonds, unbranched |
| phosphatidic acid |
basic phospholipid structure |
| cardiolipin |
an unusual phospholipids |
| 4 types of sphingolipids |
sphingosine, caramide, sphingomyelin, glycosphingolipids |
| 3 types of glycosphingolipids |
cerebroside, ganglioside, globoside |
| conversion of sphingolipids |
sphingoside + fatty acid=ceramide; ceramide + phosphatidylcholine= sphingomylin; ceramide + carbs=glycosphingolipid |
| 4 cholesterol derivatives |
1)component of biological membranes 2)bile salts 3)steroid hormones (progesterone, aldosterone, cortisol, estrogens, androgens) 4)vitamin D |
| cholesterol is synthesized from |
acetyl-CoA |
| what lipid is not transported in lipoproteins |
free fatty acids |
| chylomicron |
largest, lightest, B-48, hydrolyzed by LPL, stores triacylglycerols, formed in enterocytes, destinations are adipocytes, liver, muscle, lung |
| VLDL |
B-100, triacylglycerols, hydrolyzed by LPL, destinations are adipocytes, liver, muscle, lung |
| IDL |
B-100, cholesterol esters, destination is liver |
| LDL |
B-100, cholesterol esters, destination is peripheral cells |
| HDL |
apolipoprotein A, cholesterol esters, destination is liver |
| Avg fat intake/day |
100 gms, 40% of calories |
| Initial lipid digestion |
gastric lipase in stomach; responsible for 10-40% of fat digestion |
| Location of bile acid synthesis |
liver |
| How much bile is synthesized/lost each day |
.5 gms |
| Gms/day of bile excreted |
12-18gms/day (he said 25 in class) |
| PTL |
pancreatic triglyceride lipase; removes fatty acids from positions 1 and 3 |
| 2-monoacylglycerides |
left over from PTL action |
| FATP4 |
fatty acid transport protein 4; transports FA into intestinal epithelial cells along with diffusion |
| PLRP1 and 2 |
pancreatic lipase related proteins; very similar to PTL but can also hydrolyze lipids other than triglycerides |
| Major triglyceride lipase in newborns |
PLRP2 |
| Where are triacylglycerides reconstructed |
enterocytes, where they are packaged into chylomicrons |
| How are free fatty acids transported in the blood |
attached to albumin |
| What removes chylomicrons from the blood |
LPL |
| LPL |
lipoprotein lipase, mostly found in adipose and muscle tissue |
| apoC-II |
activator protein on the surface of lipoproteins necessary for LPL to work |
| chilomicron remnant |
what is left after the chilomicron loses its triglycerides (80-90%); hydrolyzed in hepatocyte lysosomes |
| 3 rare autosomal recessive disorders that affect chylomicron synthesis/metabolism |
abetalipoproteinemia, lipoprotein lipase deficiency, apoprotein C-II deficiency |
| abetalipoproteinemia |
defects in apo B-100; no chylomicrons, VLDL, or LDL; GI symptoms, cognative problems |
| apoprotein C-II deficiency |
LPL ineffective; too many chilomicrons |
| LPL deficiency |
liver/pancreas problems; too many chilomicrons and VLDL; give fat restricted diet |
| Olestra |
fake fat; sucrose core in place of glycerol; sucrose esterified w/ 6-8 FA |
| Orlistat |
lipase inhibitor; inhibits both gastric and pancreatic lipase |
| What might be a future target for anti-obesity drugs |
FATP4 |
| Steatorrhea |
lots of fat in stool; stool floats, stinks, and is pale; caused by GI infection, pancreatic cancer (no PTL), cystic fibrosis |
| Energy used during exercise |
ATP used in 1 second, creatine phosphate used up in 30 seconds, glycogen used in 30 minutes; if only fat were used, marathon would take at least 6 hrs |
| Only system that can’t do beta oxidation |
CNS |
| Advantages of lipid storage over carbs |
compact, twice as much energy/weight |
| Location of beta oxidation |
mitochondrial matrix with a bit in peroxisomes |
| Carnitine shuttle pathway |
carnitine+acyl CoA(CPT1)CoA+acyl carnitine [enters mitochondria] +CoA (CPT2)Acyl CoA+Carnitine [leaves mitochondria] |
| CPT |
carnitine palmitoyltransferase (can also use palmitoyl CoA) |
| 4 main beta oxidation steps |
oxidation (FADH2 formed), hydration, oxidation (NADH formed), thiolysis |
| first beta oxidation oxidation |
FAD->FADH2 and trans double bond is formed |
| beta oxidation hydration |
H2O is added, double bond turns to single bond and OH is added on beta carbon |
| second beta oxidation oxidation |
NAD->NADH, carbonyl group is formed on beta carbon |
| beta oxidation thiolysis |
CoASH attacks beta carbonyl carbon and acetyl CoA breaks off |
| # of carbons removed per round of beta oxidation |
2 |
| what % of muscle oxygen consumption is from fatty acid oxidation during prolonged aerobic exercise |
60% |
| propionate metabolism |
beta oxidation of FA with an odd number of carbons, leading to formation of 1 propionyl-CoA |
| formation of succinyl CoA from Propionyl CoA occurs where |
liver mitochondria |
| propionyl CoA to D-methylmalonyl CoA requires what |
HCO3, ATP, and biotin |
| L-Methylmalonyl CoA to Succinyl CoA requires what |
vit B12 (cobalamin) |
| Double bonds at odd-numbered positions require what |
isomerase to convert cis3 to trans2 bond |
| Double bonds at even numbered positions require |
dehydrogenase to convert cis4 to cis2 and trans4; these are reduced with a reductase to trans3 which uses an isomerase to give trans2; DH gives FADH2 and reductase gives NADP+ |
| Regulation of beta oxidation |
most occurs at acyl carnitine formation; high levels of malonyl CoA inhibit CPT1 |
| For a given weight, the recoverable energy content of fatty acid compared to glucose |
2.5X greater |
| Zellweger syndrome |
defect in degredation of long chain FA >26; no functional peroxisomes (they degrade long chain FA) |
| Refsum syndrome |
defect in degredation of 3-methyl-branched FA; autosomal recessive; must be modified by alpha oxidation in peroxisomes |
| Ketone bodies produced during starvation are produced where |
liver mitochondria |
| Ketone bodies |
acetoacetate, hydroxybutyrate with acetone as byproduct |
| Ketone body regulation |
rate of release of fatty acids from adipose tissue which is under hormonal control (glucagons, epinephrine and thyroxine stimulate, insulin inhibits) |
| Physiological ketosis |
associated with late pregnancy, neonatal period, high fat diet, starvation, sever exercise |
| Pathological ketosis |
found in insulin-dependent diabetes; total absence of insulin |
| Brain energy sources |
glucose and ketone bodies |
| Muscle energy sources |
glucose, FA, ketone bodies; resting muscle gets energy from beta oxidation |
| Heart energy sources |
FA and ketone bodies |
| Adipose tissue energy sources |
glucose, FA; needs glucose to make glycerol to make triglycerides |
| Kidney energy sources |
glucose, FA, ketone bodies |
| Liver energy sources |
alpha-keto-acids under normal conditions; FA during starvation; the liver makes glucose and ketone bodies but does not use them |
| Conversion of glucose to FA occurs where |
mostly liver |
| FA synthesis occurs where in cell |
cytoplasm |
| How does acetyl CoA leave the mitochondria |
most incorporate into citrate (some through carnitine shuttle) |
| How does the cell signal FA synthesis |
high ATP and NADH levels inhibit isocitrate DH leading to high levels of citrate |
| Are FA synthesized under high fat/low carb starvation |
NO, low carb levels deplete the oxaloacetate pool |
| Rate limiting step in FA synthesis |
malonyl-CoA formation from acetyl CoA and CO2 |
| Enzyme in formation of malonyl-CoA |
acetyl-CoA carboxylase |
| Malonyl CoA formation requires what reactants and cofactors |
acetyla CoA, biotin, CO2, ADP + Pi |
| Where else is malonyl CoA used |
NOWHERE |
| ACP |
acyl carrier protein; acyl intermediates are bound as thioester derivatives instead of CoA |
| FA synthesis steps (no enzymes or compound names other than starting two) |
acetyl ACP + malonyl ACP (condensation) acetoacetyl ACP (reduction) forms beta OH (DH) alpha double bond (reduction) four carbon FA |
| How to make odd chain FA |
start with propianyl CoA instead of acetyl CoA |
| Two sites for FA chain elongation |
ER and mitochondria |
| FA chain elongation in ER condensing unit and carbon donor |
malonyl-CoA is condensing unit and fatty acyl-CoA is carbon donor (CoA, not ACP) |
| FA elongation occurs at what end |
carboxyl end |
| FA acid synthesis and chain elongation electron donor |
NADPH |
| When and where does FA unsaturation occur |
after 16 chain FA is produced and at the ER |
| First double bond introduced in a FA |
delta 9 |
| Double bond introduction rules |
delta 9 is first, delta 5 and 6 are the other two, there must be 3 carbons (single methylene group) between each DB |
| Two essential fatty acids |
omega 3 FA linolenate and omega 6 FA linoleate |
| FA degredation vs synthesis enzymes |
degredation has individual enzymes, synthesis has one polypeptide |
| FA degredation oxidants |
NAD, FAD |
| FA synthesis reductant |
NADPH |
| Short term FA synthesis regulation |
rapid, allosteric activators/inhibitors |
| Long term FA synthesis regulation |
effects of diet, hormones and amount of enzymes, especially lipogenic enzymes |
| Lipogenic enzymes |
acetyl CoA carboxylase, fatty acid synthase, citrate lyase, malic enzyme, DH of PPP |
| Acetyl CoA carboxylase regulation |
-phosphorylation by AMPK (most important), -palmitoyl CoA, -epin/glucagons, +insulin, +citrate |
| Carnitine-palmitoyl-translocase (CPT) regulation |
allosteric inhibition by malonyl CoA (prevents beta oxidation) |
| AMPK |
AMP activated protein kinase; inactivates carboxylase by phosphorylating it |
| Purposes of adipose tissue |
energy storage, insulation, storage of soluble vitamins, synthesis of adipokines, protection of organs |
| Adipocyte numbers |
don’t change much past teen years; get larger/smaller; obese people have more; liposuction patients regrow the adipocytes removed |
| HSL |
homrone-sensitive lipase; catalyzes the breakdown of stored triglyceride in adipocytes |
| HSL activation |
glucagon/epinephrine->cAMP->PKA->phosphorylated HSL (active) |
| Adipokines |
hormones produced by the adipocytes |
| Leptin and adiponectin |
best known adipokines; decrease appetite and increase thermogenesis |
| Ghrelin |
peptide hormone produced by stomach implicated in short term and long term regulation of appetite and body weight. Injection of ghrelin into rodents increases food intake |
| Phospholipase C |
cuts the bond between glycerol and the phosphate in phospholipids |
| Sphingolipids are degraded where |
lysosomes |
| Sphingolipid diseases |
all but one are recessive; specific enzyme deficiencies resulting in accumulation of substrate in lysosomes |
| 4 major components of membranes |
phospholipids, glycolipids, cholesterol, proteins |
| T/F brain has lots of cholesterol in it’s membranes |
True |
| What % of membrane is protein in mitochondrial inner membrane and myelin sheath |
75% and 18% |
| Extrinsic protein |
can be removed by high salt concentrations b/c they are on outside of membrane |
| Intrinsic protein |
cannot be extracted with salt; must use detergents |
| What types of molecules can simply diffuse across membranes |
gases, small uncharged polar molecules |
| Important molecules that use receptor mediated endocytosis |
transport proteins (LDL), hormones, growth factors, immunoglobulins, lysosomal enzymes |
| pH of endosomes |
early endosome pH=outside of cell pH; late endosome has lower pH |
| when does a primary lysosome become secondary |
when it takes up material to be degraded |
| clathrin coat looks like what |
a polyhedral lattice |
| 4 fates of endosomes |
recycling, transcytosis, degradation, sequestration |
| transcytosis |
endosome is transported to other side of cell and maybe to another cell; used to transport mother’s antibodies to fetus |
| how do cells take up cholesterol |
endocytosis of LDL |
| T/F animals cannot synthesize cholesterol |
F |
| Rate controlling enzyme of cholesterol synthesis |
HMG-CoA reductase |
| Location of HMG CoA reductase |
ER membrane facing the cytoplasm |
| What inhibits HMG CoA reductase |
high cholesterol levels |
| All cholesterol medications attack what enzyme |
HMG CoA reductase |
| SREBP stands for |
sterol regulatory element binding protein |
| What does SREBP do |
is a transcription factor the regulates expression of both HMG-CoA reductase and LDL receptor protein |
| Where is SREBP located and how does it work |
on ER membrane; lack of cholesterol activates protease to release SREBP which goes to nucleus and activates transcription |
| FH |
familial hypercholesterolemia; deficiency of active LDL receptors which interact with LDL B100 |
| 4 types of FH |
1)no receptor synthesized 2)incomplete processing 3)receptors are processed but have a low affinity for B-100 4)receptors fail to cluster in coated pits |
| treatment for FH |
administer bile acid-binding resins and HMG-CoA reductase inhibitor |
| statins only work on FH heterozygotes or homozygotes |
heterozygotes |
| how does high cholesterol contribute to coronary heart disease |
lots of LDL in blood leads to oxidation of B-100, oxidized apo B-100 cannot bind to LDL receptors and are taken up by macrophages which uptake more and more oxLDL until they become foam cells which stick to endothelium of arteries |
Buen Viaje lv.2 ch 8
