Feb9 M1-Lipid Metabolism 1 Flashcards
lipids general definition + example
organic compound insoluble in water
FAs only have carboxyl, otherwise no polarity
lipids in cell membrane
phospholipids, cholesterol, fatty acids
lipids one fct in plasma membrane
allow motility and movement of transmembrane receptors
lipids role in brain and adipose tissue
brain: insulation for electrical transmission (change in electrical charge across plasma membranes)
adipose tissue: insulation, retain heat
what happens to TGs until absorbed + other source of lipids
digested by pancreatic enzymes to make 2-monoacyl-glycerol and fatty acids
(can also synthesize lipids in the body)
what happens to 2-monoacyl-glycerol and fatty acids in intestinal cells
resynthesized in TGs and secreted in lymphatics in chylomicrons (lipid rich) then go to blood and to liver
what liver does to chylomicrons
hydrozyles them, gets TGs again and secretes them in blood as VLDL
(IMPORTANT) starting molecule for FA synthesis and 1st rx and enzyme
acetyl-CoA (2 Cs)
1. add carboxyl group to make malonyl-CoA (3 C) by malonyl-CoA carboxylase
2nd rx to make FAs
1 (acetyl-CoA or growing FA chain) +
1 malonyl-CoA + 1 NADH = FA longer by 2 C + CO2 + NAD+ + water
rate limiting enzyme in FA synthesis
acetyl-CoA carboxylase
positive regulators of acetyl-CoA carboxylase (2)
- protein phosphatase (insulin cascade, protein phosphatase is phosphorylated, now active, it removes a P from ACC and ACC is active)
- citrate (a metabolite of TCA cycle so lot of eat shows we have enough nutrients)
negative regulators of ACC (acetyl-CoA carboxylase)
- glucagon
- E (activates PKA, prot kinase A, which will phosph ACC)
- high AMP. (sensed by AMP kinase which will phosph ACC)
- palmitoyl-CoA (end product of the whole thing)
malonyl-CoA important role
lowers FA mitochondrial uptake and degradation to make energy (don’t want to do that when synthesizing lipids)
what enzyme takes care of the synthesis of palmitate (16C) + charact
FA synthetase (FAS). massive enzyme. homodimer with 2 multifunctional (multireaction) chambers
substrates needed for palmitate synthesis by FAS
NADH (many), 1 acetyl CoA, 7 malonyl CoA (cycle of 7 rxs repeated for each malonyl-CoA added
4 things we can do with palmitate
- extend it (some enzymes can make it 18C or even more but less common)
- desaturate it (desaturases can work on carbons 4,5,6,9 starting from carboxyl)
- store it
- add it or add its derivatives to complex fatty acids
why some fatty acids are essential
can’t synthesize fatty acids with double bonds other than on carbon 4,5,6,9 so need some exogenous FAs
functions of essential FAs (that we can’t synthesize)
positive effects on cholesterol synthesis and metabolism
what storing palmitate means
make it TGs by adding this FA to glycerol (make triacylglycerol, synonym of TG)
step 1 in storing palmitate
glycerol phosphate (glycerol with P in C3) + palmitate give glycerol P with palmitate on C1 (done by acyltransferase)
step 2 in storing palmitate
add palmitate on C2 of the glycerol (get DAG phosphate, glycerol with palmitate on C1,2 and P on C3)
(done by acyltransferase)
step 3 in storing palmitate
DAG phosphate (also called phosphatidic acid) has its P removed by a phosphatase to make DAG (important signaling molecule)
step 4 in storing palmitate
DAG (signaling molecule) has FA (palmitate) added to C3 by acyltransferase
what happens in the liver with TGs made from palmitate
exported in VLDL (apoB), goes to adipose tissue, TGs broken into FFAs and glycerol
complex FAs that we can make palmitate into
can make it phospholipid or glycolipid
phospholipid composition
glycerol with 1 FA chain on C2 + one carbon with phosphate + important moiety added for membrane fluidity and structure (bc has neg charge)
glycolipid composition
glycerol with N-FA chain on middle C, FA on a side C and carbohydrate on other side carbon
platelet-activating factor composition
glycerol with P + moiety on a side C, acetyl group on middle C, saturated FA on last C
platelet-activating factor function
when released, binds receptor on platelets and affects coagulation and clotting properties
enzyme family that cleaves phospholipids and how the enzymes in the family differ
phospholipases A1, A2, C or D. depending on where they cleave the carbons of the glycerol backbone
phospholipase 2: why important component of venoms and why is toxic
- cleaves a substrate to release arachidonic acid (highly inflammatory molecule)
- toxicity to cells by binding a specific receptor
sphingomyelins composition
sphingosine molecule with N-FA on 2nd carbon (all that forms ceramide) and then moiety (like choline) added on 3rd carbon
sphingosine def
glycerol with saturated FA on 1st C
sphingomyelins function
highly present in CNS. role in electrical activity of neurons
Niemann-Pick disease pathophgy
sphingomyelinase deficiency. can’t cleave phosphochlorine off the ceramide (of sphingomyelin) and sphingomyelin accumulates
why sphingomyelinase deficiency is a problem
sphingomyelin is constantly turned over (broken down and synthesized)
hallmarks of Niemann-Pick disease
- enlarged liver and spleen filled with lipids
- mental retardation and neurodegen
- death in early childhood (type A)
what gives the glycolipids different properties
the different sugars attached on them
ganglioside GM2 structure
ceramide (glycerol backbone C1 = FA, C2 = N-FA) with glucose, galactose, and galactosamine molecules
main problems and symptoms seen in lipids metabolism defects
CNS, neuro, seizures, degeneration
Tay-Sachs disease cause
defect in beta hexosaminadase A resulting in accumulation of ganglioside GM2
2 regions of high Tay-Sachs prevalence in Quebec + how it differs
Saguenay Lac Saint-Jean region and Ashkenazi Jews. mutation is diff in the two groups
2 Tay-Sachs regions within French Canadian population + how they differ
- Saguenay Lac Saint-Jean
- Bas Saint-Laurent and péninsule du Gaspé
* two different mutations
