Ziele pt 2 Flashcards
compare fats and carbs as energy sources
fats are very dense and have the capability to be highly reduced and produce nearly twice the amount of energy than carbs per gram; fats store energy for 30 days, carbs 24 hours,
why do we use lipids for energy
it is lighter than carbs (ex. hummingbirds;
do not raise osmolarity of cytosol
energy dense/ efficient
describe overall lipid catabolism process
breakdown
TAG -> fatty acid + glycerol
where does fatty acids v. glycerol go?
FA-> acetyl CoA
glycerol -> glycolysis
describe overall lipid anabolism
excess carbs/ acetyl coa -> fatty acids or beta hydroxy-beta methylglutaryl coa (HMG CoA)
HMG-Coa -> cholesterol and ketone bodies
describe apolipoprotein
integral membrane protein acts as barcode to identify tissues/ enzymes
describe lipoprotein lipase
activated by apoC-II (apolipoprotein on chylomicron); hydrolyze TAG to fatty acid and glycerol (which returns to liver)
describe plasma lipoprotein
transport vesicle of lipids, single leaflet membrane since interior is all lipids
what is the TAG catabolism regulating step?
the phosphorylation of HSL (activation)
why do fatty acids require transporters
need carrier serum albumin since hydrophobic; at target kisses, uses transporter to get into target tissue
how can fatty acids be used
free fatty acid needs to be converted to fatty acyl-CoA to under go beta oxidation, membrane lipid synthesis, post translational modification, final step in FA synthesis
what is carnitine acyltransferase
fatty acyl coA + carnitine -> fatty acyl-carnitine
catalyzes the nucleophilic attack of hydroxyl group on carbonyl
sits on outer membrane; fatty acyl coA reformed in matrix via carnitine acyltransferase 2
describe the 3 stages of fatty acid beta oxidation
within mitochondria matrix
1. FA -> Acetyl- CoA and reduced e- Carriers
>oxidation of FAD -> FADH2-> ETC
>hydration
> oxidation: NAD -> NADH -> ETC
> attack by coash to form acetyl coa
repeat 6 times (bc each time we remove 2 C’s )
2. CAC
3. ETC & oxidative phosphorylation
what is the overall equation/ energy yield of beta oxidation stage 1
8 acetyl coa (if starting with 16C FA) 28 ATP (from FADH2 and 7NADH) and 7 H2O( water production here explains why hibernation is possible
What are the reasons Ketone bodies would are synthesized?
fasting, starvation, low carb diets, prolonged exercise, untreated diabetes
structures of acetoacetate
H3C-C=O
l
CH2
l
O-C=O
structures of beta hydroxybutyrate
H3C-C=O
l
H2- C-OH
l
O-C=O
describe keto genesis/ ketone body synthesis
occurs only in liver and mitochondria of hepatocytes
acetyl-coa -> (via thiolase) acetocacetyl-CoA -> HMG-GoA -> acetoacetate -> acetone or beta-hydroxybutyrate
beta hydroxybutyrate -> acetoacetate -> acetoacetyl-CoA -> Acetyl coA (which enters CAC)
heart prefers acetoacetate
brain prefers beta hydroxybutyrate bc extra electrons in the oxidation of NAD that is sent to ETC
what happens to ketone bodies during fasting and starvation
fatty acids return to the liver during times of low glucose so ketone bodies can be synthesized
low oxaloacetate (due to what is available being converted to glucose for the brain and other tissues that exclusively use glycolysis for energy) prevents the CAC from running so acetyl CoA is put into ketone body synthesis instead
describe fatty acid synthesis
occurs in liver and adipose in cytosol with a 3C intermediate of malonyl-CoA
energy expensive (highly regulated)
uses 7 ATP for to form 16C
- formation of malonyl CoA (where energy is inputted, biotin coenzyme, regulated by covalent modification, allosteric regulation)
- fatty acid synthase
what are the 6 enzyme activities of fatty acid synthase
- synthase - prime and bind ACP to acetyl-CoA
- transferase - reduce beta keto with NADPH
- dehydration
- 2-reductases - NADPH
- thiolase -transfer butyryl from ACP to KS, keep adding malonyl until at desired carbon numbers
- plus acyl carrier protein
what is the starting material for fatty acid synthesis and where does it come from
acetyl coa, NADPH, ATP, and protons
NADPH from PPP
acetyl coa from PDC
how is fatty acid oxidation and synthesis regulated
acetyl CoA carboxylase is inhibited by phosphorylation and palmitoyl-coa (too much product); glucagon, epinephrine trigger phosphorylation
activated by citrate and dephosphorylation; insulin activates dephospho rylation
how is TAG synthesis regulated
activated by insulin or low energy which upregulates glycolysis/ PDC and dephosphorylates ACC
how does glucagon regulate fatty acid synthesis
ACTIVATES: HSL, inc. fat mobilization, inc. gluconeogenesis
INHIBITS: ACC, PDC, dec. FA synthesis
how does insulin regulate fatty acid synthesis
ACTIVATES: ACC, PDC, inc. FA synthesis
INHIBITS: HSL, dec. mobilization of fats, dec. gluconeogenesis, inc. glycolysis
how does allosteric control regulate fatty acid synthesis and breakdown
palmitoyl CoA (fatty acid synthesis product) inhibits synthesis by inhibiting ACC
ACC activated by citrate
carnitine acyltransferase I is inhibited by malonyl-CoA
describe how a low carb diet influences fatty acid regulation
inc. glucagon, FA released from adipocytes
FA synthesis dec., FA oxidation inc. with acetyl CoA increasing, glycolysis dec., malonyl coa dec. carnitine acyltransferase I increases and FA into mitochondrion increases, oxaloacetate used for gluconeogenesis, CAC slows and citrate synthesis dec., inc. ACC accumulation, ketone bodies inc. and use in brain increases, ketone bodies increase in plasma and urine which can lead to keto acidosis
describe how a high carb diet influences fatty acid regulation
insulin increases, inc. use of GLUT4 transporters and FA release inhibited, excess carbs is oxidized form increased ATP synthesis and increased concentrations of citrate
ACC dephosphorylated (activated) molonyl CoA inc. and FA synthesis inc.
citrate lyase inc. transport more acetyl coa to cytosol
oxaloacetate levels inc. and NADPH levels increase
malonyl CoA levels increase, carnitine acyltransferase I is inhibited and there is dec. FA in mitochondria
what are the symptoms/ causes of Reye’s syndrome
accumulation of fat in liver, cerebral edemaa, swollen mitochondria, hyperammonemia, hypoglycemia; associated with inc. FA and AA; bad oxidation
what pathway’s dysfunction will result in hypoglycemia? how?
impacted gluconeogenesis/ pyruvate carboxylase and low acetyl coa
what pathway’s dysfunction will result in fat accumulation in the liver? how?
impacted beta oxidation/ beta hydroxyacel-CoA dehydrogenase inhibited by hydroxyhipporate
what pathway’s dysfunction will result in low energy? how?
impacted ketogenesis/ inhibited and low acetyl CoA levels
what pathway’s dysfunction will result in hyperammonemia and cerebral edema? how?
impacted by urea cycle/ slowed by lack of ATP and low NAG (can’t activate CPM-I
what pathway’s dysfunction will result in low ATP? how?
impacted electron transport/ slowed by lack of NADH/ FADH2
where does cholesterol synthesis occur?
in the cytosol of any cell with a mitochondria
what is cholesterol
4 fused rings and an alkyl side chain
every carbon comes from acetate; 30C
what is an isoprene
building block intermediate 5C
describe cholesterol biosynthesis (4 steps)
- 3 acetate to mevalonate (6C) via thiolase, HMG CoA synthase and HMG CoA reductase(uses 2 NADPH /rate determining step)
- mevalonate to activated isoprene via 3 ATP and releases CO2 and PPi (main energy stage)
- begin assembly:activated isoprene (5C) to squalene (30C) by 5C+ 5C -> 10 C + 5 C -> 15C + 15C -> 30 C
*squalene synthase to finish, using NADPH - squalene -> cholesterol (ring closure by using cyclase, O2 and NADPH to produce H2O and NADP+)
how is cholesterol biosynthesis regulated in the short term?
activated via insulin, ACAT, dephospho rylation of AMP kinase
inactivated via glucagon, low energy, phosphorylation of AMP Kinase
how is cholesterol biosynthesis regulated in the long term?
gene transcription is inhibited with high sterol and activated with low sterol to Golgi
what are plasma lipoproteins? what is their function?
transport molecules to move the highly hydrophobic molecules
single leaflet membrane
describe chylomicrons in terms of where they are, density, and pathway involved in.
low density, mostly TAGs, formed in intestinal cells from diet TAG, in exogenous pathway working to export dietary TAG into blood and into gallbladder
describe VLDL in terms of where they are, density, and pathway involved in.
very low density, not as low as chylomicrons; formed in liver, in endogenous pathway which produces free fatty acids
describe LDL in terms of where they are, density, and pathway involved in.
low density, not as low as VLDL; deriver from VLDL, in endogenous pathway which produces free fatty acids
describe HDL in terms of where they are, density, and pathway involved in.
high density (mostly protein), formed in liver, in reverse transport which scavenges to return excess cholesterol to liver “ good cholesterol”
describe receptor-mediated endocytosis of LDL at target cells
LDL receptors on muscle/heart/ and other target cells are expressed; binds LDL to lysosome for use in membrane, sterol, and bile acid syntheisis
describe TAG catabolism
- bile salts mix dietary fats in small intestine
- intestinal lipases degrade TAG
- epithelial cells take in and convert to TAG the body recognizes
- TAG made into chylomicrons (plasma lipoproteins)
- chylomicrons move through blood
- lipoprotein lipase activated by apoC-II in capillary breaks down TAG to glycerol and FA
- FA oxidized as fuel or stored
describe TAG catabolism
storage fat (adipocyte): signaled by glucagon (low blood glucose) or epinephrine (energy demand) which activates a G-protein receptor that activates PKA
PKA phosphorylates the enzyme that releases Hormone-Sensitive Lipase (HSL) which activates another lipase;
breakdown of TAG requires a sequential pleating of FA groups off glycerol head (by ATGL); free fat acids
what is the importance of using NADPH in ketone body synthesis
NADP+ activates pentose phosphate pathway that increases glycolysis;
