TBL 7 Lipid Metabolism Flashcards
B-oxidation of fatty acids occur in the _________ of the cell, and gives rise to form ______.
mitochondria; acetyl-CoA
(Saturated/unsaturated) fatty acids have a higher melting point. They are thus solids at room temperature.
Saturated
Fats are stored in the cytoplasm as _________ compounds.
triacylglycerol (TAG)
Fats are stored in ____ cells.
adipose (fat cells)
Bile salts are generated from ______ in the _____ and stored in the _______.
generated from cholesterol in the liver, stored in gallbladder
Bile salts _____ bulky fat globules in the intestine.
emulsifies
_______, also known as fatty stool, is a symptom due to the lack of bile salts which causes indigestion and malabsorption of fats into the blood, causing most of the fat to pass through the gut undigested.
Steatorrhoea
Bile salts have a hydrophobic and hydrophilic face and form ______ in aqueous environment to shield hydrophobic TAGs form the solution.
micelles
Bile salts increase the surface area of TAGs for ______ to bind and digest TAGs.
pancreatic lipase
Once the TAGs are incorporated into chylomicrons, these lipoproteins enter the ______ and are transported by the _____ and returned to the blood.
enter the lacteal and are transported by lymph
Orlistat inhibits _____, reducing fat absorption in the intestines and undigested fat is excreted through faeces.
gastric and pancreatic lipase
1st step of B-oxidation:
Fatty acid —> ________ by enzyme _______. This step utilises 2 high energy bonds of ATP, and occurs on the ____________.
Fatty acid is converted to acyl-CoA, by acyl-CoA synthetase.
Occurs on the outer mitochondrial membrane
2nd step of B-oxidation:
Acyl-CoA produced has to be transported from the outer mitochondrial membrane into the ____. This is done via the _______ shuttle.
Acyl-CoA has to be transported into the mitochondrial matrix. This is done via the carnitine shuttle.
How the carnitine shuttle works:
Acyl-CoA will be coupled with carnitine to form ________ by enzyme _____, and is moved to the matrix by a ______.
Acyl-carnitine is then converted back to carnitine by ____, transferring the acyl group to CoA to reform _______.
How the carnitine shuttle works:
Acyl-CoA will be coupled with carnitine to form Acyl-carnitine by enzyme CAT I, and is moved to the matrix by a translocase.
Acyl-carnitine is then converted back to carnitine by CAT II, transferring the acyl group to CoA to reform acyl-CoA.
3rd step of B-oxidation:
A) Acyl-CoA will first be ______ by enzyme _________.
Cofactor ____ is reduced in the process, forming ____.
A) Acyl-CoA will first be oxidised by enzyme acyl-CoA dehyodrogenase.
(H atoms are removed from alpha and beta C, forming C=C bond).
Cofactor FAD to FADH2.
3rd step of B-oxidation:
B) Intermediate then undergoes hydration by enzyme ________.
enzyme 3-hydroxyacyl CoA hydrolase
OH group added to beta C, H atom added to alpha C
3rd step of B-oxidation:
C) Intermediate then undergoes ________ by enzyme ________.
Cofactor ___ is reduced in the process, forming NADH.
Intermediate undergoes oxidation by enzyme 3-hydroxyacyl CoA dehydrogenase.
(removal of H atom at Beta C to form C=O group)
Cofactor NAD+
3rd step of B-oxidation:
D) Intermediate then undergoes ______ by enzyme __________, forming one molecule of acetyl-CoA and a shortened molecule of acyl-CoA.
The cycle repeats until the last cycle where 2 acetyl-CoA molecules are produced.
Intermediate then undergoes thiolysis by enzyme thiolase.
Palmitic acid (fatty acid) consists of ___C. It is used to produce pamitoyl-CoA, which undergoes __ cycles of B-oxidation to produce __ molecules of acetyl-CoA.
16 Carbons atoms
7 cycles of B-oxidation; 8 molecules of acetyl-CoA
For odd-numbered fatty acids, the last cycle of B-oxidation will result in the production of a 3C propionyl-CoA, which will be converted to ________ which can enter the Krebs’ cycle.
Succinyl-CoA (4C)
In the first step of B-oxidation where acyl-CoA is oxidised using enzyme acyl-CoA dehydrogenase, there are 5 different types of enzymes specific to the _____ of fatty acid chains.
length
Fact: Primary carnitine defiency is due to a loss-of-function mutation to the gene which encodes a carnitine transporter. This causes reduced ability to take up carnitine required for B-oxidation.
No answer needed :)
______ is the proccess of producing fatty acids from acetyl-CoA and malonyl-CoA via sequential decarboxylative condensation reactions.
Lipogenesis
The enzymes involved in lipogenesis are:
1)
2)
1) Acetyl-CoA carboxylase
2) Fatty acid synthase (FAS)
Fatty acid synthase (FAS) consists of 9 different domains and 7 different enzymes. These 7 different enzymes are:
A and B are involved in transferring ACP group onto acetyl-CoA and malonyl-CoA.
C is involved in the next step of condensation between acetyl-ACP and malonyl-ACP to form B-ketoacyl ACP.
D is involved in the following step of reduction to form 3-hydroxyacyl ACP.
E is involved in the following step of dehydration.
F is involved in the last step of reduction, to form a R group.
A and B: Acetyl-ACP transferase; Malonyl-ACP transferase;
C: B-ketoacyl synthase;
D: B-ketoacyl reductase;
E: 3-hydroxyacyl-ACP dehydrases 1 and 2 (dehydration);
F: Enol-ACP reductase
Desaturation of fatty acids (to form unsaturated fatty acids) involve the enzyme ___________.
Fatty acyl-CoA desaturases
Dietary cholesterol uptake in humans is limited to approximately ___g/day.
0.5
Cholesterol biosynthesis takes place in the (organ).
liver
Cholesterol biosynthesis takes place in three main steps:
1) Generation of ________ (a reduced 3x acetyl-CoA molecules)
2) Activation of melovanate to ________ (C5 precursor isoprene unit) which is then elongated to form ______ (C30).
3) Cyclisation and ________ of squalene to form cholesterol. (C27)
1) Generation of mevalonate (C6)
2) Activation of mevalonate to isopentenyl-PP (C5) which is then elongated to form squalene. (C30)
3) Cyclisation and demethylation of squalene to form cholesterol
In mevalonate synthesis, __ acetyl-CoA molecules come together to form ________, which is then reduced by _________ to form mevalonate.
3 acetyl-CoA molecules come together to form HMG-CoA (6C), which is then reduced by HMG-CoA reductase to form mevalonate.
Statins competitively binds to _______, and thus they are used to block the synthesis of mevalonate from acetyl-CoA, inhibiting cholesterol synthesis.
HMG-CoA reductase
HMG-CoA is under ______ feedback control by bile salts, cholesterol and mevalonate.
negative
Mevalonate (C6) then undergoes sequential ________ at the hydroxyl groups at positions 3 and 5 to form _________ (C6). This is then decarboxylated to form isopentenyl-PP (C5), which is isomerised to form ____________ (C5).
Mevalonate (C6) —> Mevalonate-3-phospho-5-pyrophosphate (C6) —> Isopentenyl-PP (C5) —-> 3,3-dimethyl PP (C5)
3,3-dimethyl PP (C5) then undergoes condensation with another unit of _________ to form _________ (C10).
Third isopentenyl-PP is added to form the intermediate __________ (C15), two of which condense to form squalene (C30) and two pyrophosphates.
3,3-dimethyl PP (C5) + Isopentenyl-PP (C5) —-> Geranyl PP (C10)
Geranyl-PP (C10) + Isopentenyl-PP (C5) —-> Farnesyl-PP (C15)
2x Farnesyl-PP (C15) —> Squalene (C30)
Condensation of 2 x Farnesyl-PP to squalene is driven by the reducing power of ______.
NADPH (cholesterol biosynthesis)
Squalene (C30) is cyclised to cholesterol by first being reduced by ___ and _____ to form squalene-2,3-epoxide.
O2 and NADPH
The enzyme _____________ catalyses the formation of lanosterol from squalene-2,3-epoxide.
Squalene epoxide lanosterol-cyclase
Lanosterol is then reduced, with the removal of ________ to form cholesterol.
3 methyl groups
The steroid precursor _________ is derived from cholesterol via the action of the enzyme _______.
Steroid precursor pregnenolene is derived from cholesterol via the action of desmolase.
