Lipids Metabolism Flashcards
biological functions of lipids
- principal source of stored energy
- major structural elements of biological membranes e..g, phospholipids, glycolipids and cholestrol
- play important roles in metabolism: enzyme cofactors, electron carriers, emulsifying agents in the digestive tracts
- intra and inter signalling event: precursors of steroid hormones
are triglycerides hydrophobic or hydrophilic?
hydrophobic
what is beta oxidation
oxidative process that releases free energy from breaking down fatty acid chains to CO2 and H2O.
the process of beta oxidation
Palmitoyl CoA–(acyl dehydrogenase)/FAD-FADH2–> Enoyl CoA–(enoyl CoA hydratase)/H2O—> b-hydroxyacyl-CoA—(b-hydroxyacyl-dehydrogenase)/NAD+-NADH–>b-ketoacyl-CoA—(b-ketothiolase)–> Acetyl Coa and 14C CoA
how many NADH, FADH2 and Acetyl CoA does beta oxidation yeild?
1 NADH, 1 FADH2, 1 Acetyl CoA
how many ATP does one NADH yield
3 ATP
how many ATP does one FADH2 yield
2 ATP
how many ATP does one Acetyl CoA yield
12 ATP
how many ATP does palmitoyl CoA yield
131-2=129 ATP (2 used for the beta oxidation process)
how does glucagon regulate lipid metabolism
triglycerides are broken down to glycerol and fatty acid chains by hormone sensitive lipase.
When blood glucose levels drop, the pancreas produces glucagon which triggers further release of lipase and increases the breakdown of stored triglycerides into glycerol and fatty acids which can be used to produce energy
where does the addition of CoA to fatty acid happen and what enzyme??
once inside the target cell where the fatty acid can be metabolised- which is any cell with mitochondria, but mostly liver cells.
Fatty Acid —(fatty acyl CoA synthetase)/ATP-ADP—> Fatty acyl CoA
why is the carnitine shuttle system used
Acetyl CoA cannot cross the mitochondrial membrane and the fatty acid CoA needs to access the mitochondrial matrix to be able to be metabolised. Therefore the carnitine shuttle system is used.
explain the carnitine shuttle system
Fatty-acyl CoA + Carinitine Acyltransferase 1 (CAT1) -> Fatty acylCAT + CoA—-(crosses the mitochondrial membrane)—-> CAT2 reverses the process to remake Fatty acyl CoA + CAT1. CAT1 then travels back across the mitochondrial membrane to repeat the process.
what can inhibit the action of CAT1
malonyl CoA
what is the rate limiting step of beta oxidation
carnitine shuttle
what mutations causes the SIDS?
sudden infant death syndrome- disorders of beta oxidation
most common mutation- one of the acyl CoA dehydrogenase enzyme catalysing the first step of oxidation of beta oxidation of a fatty acyl-CoA.
there are other mutations that can cause SIDS, but this is the most common
where does fatty acid synthesis occur?
adipocytes and liver
how does glucose get converted to acetyl CoA
increase of glucose levels encourages the pancreas to produce insulin and allow cells to take in and process a lot more glucose. in glycolysis, glucose breaks down to 2pyruvate molecules releasing ATP, and further more, the pyruvate molecule in the mitochondria gets converted to Acetyl CoA by the enzyme pyruvate dehydrogenase.
citric acid cycle
Acetyl CoA and Oxaloacetate —-> Citrate —–> electron carriers that can be used in the electron transport chain.
what cycle enables the acetyl CoA to be moved from the mitochondria to the cytoplasm
citrate malate cycle
action of pyruvate caroxylase
increase in acetyl CoA conc in mitochondria can increase activity of pyruvate carboxylase that can further catalyse the conversion of pyruvate to oxaloacetate which is used in the Citric Cycle
the citrate malate cycle
citrate leaves the mitochondria to the cytoplasm and by the action of citrate lyase breaks down to oxaloacetate and acetyl CoA.
the oxaloacetate then by the action of malic enzyme breaks down to pyruvate (NADP+-> NADPH) which can travel across the membrane from the cytoplasm to mitochondria
what two conditions ensure fatty acid synthesis
- acetyl CoA in cytoplasm 2. presence of NADPH
what is the rate limiting step of fatty acid synthesis (explain the process)
acetyl CoA in the presence of Acetyl CoA carboxylase and HCO3- converts to Malonyl-CoA (3C)
how is Acetyl-CoA carboxylase regulated?
hormones and allosteric
explain the hormonal regulation of Acetyl-CoA
insulin can decrease the activity, glucagon can increase the activity
explain the allosteric regulation of acetyl-CoA
citrate can increase the action and fatty acids can decrease the action
explain the fatty acid synthesis process
- acetyl CoA converts to malonyl CoA
- Acetyl CoA breaks down to CoA and Acetate in the presence of Acetyl-CoA ACP transcyclase
- Acetate binds to the ACP end and spontaneously transfers to the Cys end
- Malonyl-CoA breaks down to Malonate and CoA in the presence of malonyl-CoA ACP transcyclase and attaches to the ACP end
- Malonate in the presence of 3-Ketoacyl ACP synthase breaks down into CO2 and Acetate. (the breakdown to CO2 produces NADPH-> NADP+)
- Acetate + Acetate –(NADPH–> NADP+)–>4C molecule on the Cys end.
Step 4 repeats until a 16C palmitoyl CoA molecule forms.
the yield from the formation of one 16C palmitoyl-CoA
8 Acetyl-CoA, 14 NADPH
where is palmitoyl stored after formation
liver as triglycerides until the need to break down to ATP
what is cholesterol synthesised from
Acetyl-CoA
what form is cholesterol eliminated as
bile acids
what enzyme catalyses the formation of cholesterol esters and where
Acyl-CoA cholesterol acyltransferase in the liver
function of LCAT
lethicin Cholesterol Acyltransferase makes cholesterol ester enter the blood stream to trap cholesterol inside lipoproteins for transport
what is cholesterol a precursor to
VitD, steroids, bile acids
why is there an emphasis on recycling cholesterol
it is a large complex molecule and there is a high energy cost of production. therefore, cells can absorb cholesterol from diets and there is a emphasis on recycling e.g., bile acids.
cholestrol molecule is a. hydrophobic b. hydrophilic c. amphipathic
c. amphipathic
bile acids is a. hydrophobic b. hydrophilic c. amphipathic
a. hydrophilic
route of bile acids in the body
produced from cholesterol in the liver and excreted into the gall bladder for release into the small intestine, but bile acids can be reabsorbed by the gut and recycled.
the name for pathway/cycle to form cholestrol
mevalonate pathway
explain the mevalonate pathway
- 2 x acetyl CoA forms acetoacetyl-CoA in the presence of Acetyl-CoA Acyl- transferase (ACAT)
- acetoacyl-CoA + HMG-CoA synthase forms HMG CoA + CoA
- HMG-CoA to mevalonate in the presence of HMG-CoA reductase (releases CoA-SH and H2O)
- Mevalonate in the presence of ATP and mevalonate-5-kinase forms mevalonate-5-phosphate
- mevalonate-5-phosphate in the presence of phosphome valonate kinase and ATP forms mevalonate pyrophosphate
- mevalonate pyrophosphate in the presence of mevalonate pyrophosphate decarboxylase forms isopentenyl pyrophosphate x 3
- isopentenyl pyrophosphate in the presence of geranyl transferase forms 2 x farnesyl pyrophosphate (15C)
- farnesyl pyrophosphate (15C) in the presence of squalene synthase forms squalene (last linear precursor to cholesterol)
- cyclisation of squalene in the presence of oxidosqualene cyclase to form lanosterol
- lanosterol –> 7-dehydrocholestrol –> cholestrol
what is the rate limiting step of the mevalonate pathway
HMG-CoA to mevalonate in the presence of HMG-CoA reductase
reasons for why lipids need to be transported
- bring dietary lipids to cells for energy production or storage
- more lipids from storage in adipose tissue for use in energy production
- provide lipids from the diet to cells for synthesising cell membranes
- carry cholesterol from peripheral tissues to the liver for excretion
- short-chain fatty acids are transported bound to blood proteins like albumin
lipoproteins are a. hydrophobic b. hydrophilic c. amphipathic
trick question- they can be composed of all three
apolipoproteins
specific carrier proteins combine with lipids to form several classes of plasma lipoproteins
why determines the function of a specific apolipoprotein
-point of synthesis -lipid composition -apolipoprotein content
chylomicron
largest (50-200nm), least dense
exogenous lipid transport
key lipoproteins: ApoE, ApoC-II
84-89% TG, 1-3% cholesterol, 3-5% cholesterol esters
VLDL
28-70nm, endogenous lipid transport
key lipoproteins: ApoE, ApoC-II
50-65% TG, 5-10% cholesterol, 10-15% cholestrol esters
LDL
20-25nm, endogenous lipid transport
key lipoprotein: ApoB-100
7-10% TG, 7-10% cholesterol. 34-40% cholesterol esters
HDL
High density lipoproteins 8-11nm
Reverse transport
key lipoproteins: ApoE
3-5%TG, 3-4% cholesterol, 12% cholesterol esters
which lipoproteins use ApoE
Chylomicron, VLDL, HDL
which lipoproteins use ApoC-II
chylomicron, VLDL
which lipoproteins use ApoE
HDL
2 major steps in the digestion of dietary TGs
- TGs need to be emulsified by bile acids
2. TGs are hydrolysed by the enzyme pancreatic triacylglycerol lipase
process of breaking down fat globules by lipase
bile sale break down fat globules into smaller globules and free fatty acids+ monoglycerides and lipase (from SI, saliva and pancrease) attaches to these smaller globules and further breaks them into free fatty acids+ monoglycerides which assembles as mixed micelles which have a hydrophobic interior and hydrophilic exterior
the route of the mixed micelles after processing by lipase into the intestinal mucosa
- the bile salts leave the micelles leaving behind free fatty acids and monoglycerides that can travel into the intestinal wall (enterocytes) where they assemble as triglycerides.
- chylomicron then carries the triglycerides to the lacteal (lymph node) and via the thoracic duct, releases the triglycerides into the blood stream, bypassing the portal system.
- the triglycerides (as fatty acids and TGs) is released into peripheral tissues such as muscles for energy and adipose tissues for storage
- the chylomicron then shrinks and then taken in by endocytosis by the liver after release. the liver recognises the remnants by the ApoE content
define endogenous tranport
transport of lipids from the liver to the adipose tissue or muscle tissue as VLDL lipoproteins
explain endogenous tranport
ApoC-II activates tissue bound lipoprotein lipases which releases fatty acids. Triacylglyceride depleted remnants of CDLs from IDLs which on further loss of triacylglycerides becomes LDLs. These cholesterol/cholesterol ester rich lipoproteins are taken up by endocytosis within extrahepatic tissues by binding of the ApoB-100 apolipoprotein to the LDL receptors on the cell surface of the liver and extrahepatic tissues
Reverse transport definition
returning cholesterol from the extrahepatic tissues to the liver
reverse transport explain
endogenous cholesterol and cholesterol esters are transported from the extrahepatic tissues back to the liver via HDL. these do not enter the liver by endocytosis but rather by attachment to scavenger receptors SR-B1 on the cell surface that media transfer of cholesterol into the cell.
Regulation of intracellular cholesterol (short-term)
cellular cholesterol levels are controlled by regulating LDL-cholesterol uptake and biosynthesis
short-term: regulation achieved by modifying HMG-CoA reductase activity: controls biosynthesis of cholesterol.
Regulation of intracellular cholesterol (long-term)
Regulation achieved by modifying numbers of molecules involved in maintaining cellular cholesterol levels
HMG-CoA and LDL Receptors
transcription and protein production increase under low cholesterol levels, repressed under high levels.
protein degradation of HMG-CoA and LDL receptors reduce numbers under high cholesterol levels.
regulation of LDL uptake by cells
mediated by LDL receptors on cell surface binding to ApoB-100–> LDL receptors separated from LDL and recycled back to cell surface —> Endosome fuses with lysosome: lytic enzymes degrade ApoB-100, releasing amino acids, fatty acids, cholesterol and cholesterol esters
