Lipid Synthesis Flashcards
What are triglycerols?
Main storage form of FA in the body
Where/when are FA synthesized?
From: acetyl CoA in liver cells
When: whenever ingested calories exceed the requirement for energy
What happens to isocitrate dehydrogenase in conditions of excess energy?
Inhibited by high NADH/NAD+ ratio, drives citrate toward fatty acid synthesis
What are the two functions of pyruvate/malate cycle in lipogenesis?
- transport acetyl CoA from mitochondria to cytosol
2. Malic enzyme generates NADPH to power fatty acid synthesis
What is the first key regulatory step in FA synth?
Cytoplasmic Acetyl co A > malonyl CoA by addition of Co2
ACC–ACETYL COA CARBOXYLASE (biotin is cofactor)
How is the fist key regulatory step regulated in the forward direction?
FORWARD–Occurs in fed state when we want to store fat
- Citrate–allosterically activates
- Insulin– increases transcription
- Xylulose 5P– increases transcription (interm of pentose phos pathway, activates transcription at acetyl coA promoter)
- Insulin- stimulates dephosphorylation of activating enzyme
How is the first key regulatory step inhibited?
- Palmitoyl coA allosterically inhibits
- Phosphorylation by AMP-PK inhibits
- Glucagon–> cAMP –> PKA –> inhibitory phosphorylation
Why is malonyl CoA also a key regulatory step?
The body/hepatocytes dono’t want to synthesize fatty acids at same time that it’s oxidizing acids. Inhibits carnitine palmitooyl transferase 1, preventing B oxidation of newly synthesized FA
What is the reaction sequence in beta oxidation of fatty acids?
Oxidation
Hydration
Oxidation
Bond cleavage
In mitochondria, multiple proteins each step
What is the reaction sequence in FA synthesis?
Bond formation
Reduction
Dehydration
REduction
Cytosol, 1 enzyme compartment carries out all 4 steps
What is the Fatty acid synthase?
A large enzyme with multiple activites.
Has 2 important S atoms.
1. from a phophopantetheinyl (V5) group covalently linked to a serine residue on acyl carrier protein subunit of FAS. Provides active S.
2. From a cysteine side chain on another protein subunit of FAS.
What are the activites of FAS?
- Bond formation
-two CC units are added to S1, then transfered to acyl chain on cystein S
-first two carbon units from acetyl co a, second from malonyl CoA - Reduction– keto group is reduced to alcohol. Nadph oxidation powers rxn
- Dehydration rxn removes water and introduces a CC double bond
- Reduction–CC double bond is reduced, oxidation of NADPH +H powers reaction
THIS FORMS A 4 C FATTY ACID CHAIN.
4 C fatty acid is transfereed from PPP S to the cysteine S, new malonyl CoA can bind to the PPP S and chain elongation continues until acyl chain is 16 C long.
How does fatty acid chain elongation occur?
Palmitoyl CoA is elongated 2 C at a time in the ER.
Malonyl CoA donates 2 C, then added keto group undergoes R,D,R to produce saturated FA chain.
When can the body unsaturate CC bonds?
When the are at least 9 c away from omega end
What omega fatty acids are essential dietary precursors for synthesizing epicosonoids?
Omega 3, Omega 6
From plant and fish oils
Need dietary source with unsaturations further on
How do we unsaturate fatty acids?
O2 is the e acceptor for creation of CC double bonds by fatty acyl coA desaturase. Powered by NADH
Arachidonic acid is a precursor for what lipid?
Prostaglandins
Can’t be synthesized new, because it has cc double bond to close to the omega carbon
How does linolenic acid lead to the creation of arachidonic acid?
Linolenic acid consumed in diet
Converted to arachidonic acid by elongation and introducing 2 cc double bonds
What happens to FA after they are synthesized in the liver?
They’re packaged as triacylglycerides, glycerophospholipids, ether phospholipids, sphigolipids
What is triacylglycerol made of?
3 fatty acyl chains linked to glycerol backbone
Glycerol 3 P is the source of the glycerol backbone
What happens to newly synthesized triacylglycerols?
In the Golgi, they’re packaged with apoprotein B100 to become LDLs
What do LDLs do?
They form secretory vesicles which fuse with plasma membrane and release VLDL into the blood
What do VLDLs do?
CIrculate and React with lipoprotein lipase (LPL at lumen of capillary endothelial cells.
LPL cleaves off FA, which then enter cells. They undergo beta oxygenation for energy in muscle cells and are stored as fat in adipocytes tissue.
What happens to triacylglycerol’s backbone?
It is recycled
Where are glycerophospholipids used and what are they constituents of? What is there structure?
Used in cell membranes Constituents of: lipoproteins bile lungsufactant Like triacylglycerol, but "head group" is attached to first C with Phosphate bond
What are common glycerophosphates?
phophatidyl–choline/ethanolamine/serine/inositol bisphosphate
use GLYCEROL as backbone
What is cardiolipin?
Component of the inner mitochondrial membrane
Formed by linking phosphatidyl glycerol with CDP diacylglycerol
**Inner mitochondrial membrane is depleted in cholesterol and rich in cardiolipan, gives it impermeable nature
What is phosphatidylinositol bisphosphate?
MEMBRANE phospholipid cleaved by phopholipase C to produce second messengers diacylglycerol and phosphoinositol triphosphate
What are ether glycerolipids/plasmalogens?
Similar to glycerophospholipids but have ETHER linkage on 1 carbon of hte clhycerol backbone.
ETHER LINK is derived from dihydroxyacetone P, a glycolysis intermediate.
What role do plasmalogens play in the body?
Component of the MYELIN SHEATH of neurons.
PLATELET ACTIVATING FACTOR uses choline as a head group and mediates allergic responses.
What are sphingolipids?
Use ceramide (derived from serine and palmitoyl CoA) instead of glycerol for their backbone
What is the most important sphingolipid?
Shingophospholipid sphingomyelin, present in the myelin sheaths of nerve fibers. Head group is choline
Describe the structures of the glycolipids cerebroside, gangliosides and globosides.
Cerebrosides and Gangliosides use serine for a backbone
Cerebrosides–are ceramide pluse glucose or galactose attached to hydroxy-methyl group
Globosides have 2 or more sugars.
Gangliosides–oligosaccharides plus NANA
What are surfactants?
Surfactants are required in the lungs to prevent alveolar collapse
- -Most abundant lung surfactant is dipalmitoylphosphatidylcholine
- -Sphingomyelin
How are the surfactants sphingomyelin and phosphatidylcholine an indicator of gestational progress?
The ratio of sphingomyelin to phosphatidylcholine in amniotic fluid is indicator of gestational progress
–early developments are similar, but as lungs develop more concentration of phosphatidyl choline increases
Where are the triacylglycerol storage sites and what is their role related to peptide hormones?
Apidocytes
Release peptide hormones, LEPTIN AND ADIPONECTIN, related to appetate and metabolism
What is leptin?
Satiety hormone
Triacylglyceride levels high, leptin secretion increases
Acts through JAKSTAT receptors in hypothatlamus
Leads to release of anorexigenic factors that depress apetite
What is adiponectin?
Complementary to leptin
Adiponectin receptors signal though amp-pk and PPAR leading to suppression of FA synthesis and increased FA oxidation
What happens to adiponectin in obesity?
It decreases
