Biochem Lec 20-21

Question 1

what is triacylglycerol

Answer 1

also known as triglyceride or TAG and the structure consist of a glycerol backbone attached to three fatty acid chains, also known as acyl chains, as this is where extra carbons are stored
these fat molecules are mainly stored in fat cells, muscle and other tissue

Question 2

what does it mean to be saturated and how is that important in fats

Answer 2

fatty acyl chains are saturated, meaning they have no double bonds between the carbons, and that is important to allow close packing
the chains in TAG need ti be hydrolyzed off to be used

Question 4

what is the overview on fat metabolism

Answer 4

the TAG stored in fat cells will be hydrolyzed, broken, into glycerol and fatty acids where the glycerol goes to liver cells and undergo gluconeogenesis to become glucose while the fatty acids chains go to also liver and other tissues to undergo fatty acid oxidation to become Acetyl CoA that get used in citric acid cycle
both end up generating energy

Question 5

what will cause fatty acids to break and get transported from cell into other tissues to undergo beta oxidation

Answer 5

the hormones epinenphrine and glucagon which are active during fast state will cause intracellular signalling through GPCRs to activate lipase, the process of signalling involve the GPCR when stimulated will activated the adenylyl cyclase which converts ATP to cAMP and that will activate protein kinase A which will phosphorylate triacylglycerol lipase and phosphorylated lipase will hydrolyze ester bonds to produce the free fatty acids and glycerol by breaking triacylglycerol into diacylglycerol and then into monoacylglycerol and by other lipases that will lead to product of 1 glycerol and 3 fatty acid chains

Question 6

which enzyme is the hormone sensitive lipase

Answer 6

triacylglyerol lipase is the hormone sensitive lipase

Question 7

what transports the fatty acid chains after they have been freed

Answer 7

albumin will transport them in the blood

Question 8

how are free fatty acids activated in cytoplasm

Answer 8

the acyl chains will get trapped in cell by covalent addition of coenzyme A and the acyl CoA synthase enzyme, a ligase that uses ATP, will form the fatty acyl CoA molecule and the pyrophosphate (PPi) get hydrolyzed into 2 phosphate groups as that is favourable and what drive the reaction in forward direction

Question 9

how is the side reaction of hydrolyzing pyrophosphate important for acyl CoA molecule

Answer 9

the reaction of breaking the pyrophosphate intop 2 phosphate groups will drive the reaction of forming acyl CoA and keeping it from going back

Question 10

what makes ATP–>AMP energetically favourable

Answer 10

this reaction is so efficient that it is responsible for 95% of the ATP made from oxidative phosphorylation as it uses ADP as subtrate since ATP synthase can only bind ADP where the reaction go as: AMP+ATP–>2ADP–>2ATP, where the first part is catalyzed by adenylate kinase and the second part is catalyzed by ATP synthase

Question 11

what is the energy required for fatty acid activation by CoA

Answer 11

the process require 2ATP as one will be ised for activation and other to produce ADP and the enrgy to keep acyl CoA and 1water molecule will be needed to hydrolyze PPi

Question 12

where does beta oxidation occur and how does it get to where it needs to

Answer 12

so acyl CoA is made in cytoplasm but beta oxidation occur inside matrix so the acyl CoA has to access the matrix but it cna only enter the mitochondrial inner memrbane by the porins and is too large and water soluble to cross into matrix so requires the help of shuttle

Question 13

what is the way that carnitine shuttle allow for acyl CoA to get into matrix

Answer 13

the shuttle consist of two enzymes and a translocase where the carnitine acyltransferase I (CAT I) enzymes is found in cytoplasmic side while the carnitine acyltransferase II (CAT II) is found in the matrix side
the CAT I will convert carnitine into acyl carnitine by transfering the acyl group of acyl CoA to carnitine and then this acyl carnitine gets translocated into matrix side by translocase enzyme of the shuttle and once in matrix then CAT II will transfer the acyl group from acyl carnitine to CoA and make acyl CoA again and free carnitine to be reused

Question 14

what is point of making the fatty acyl CoA outside the matrix if it is only used in matrix

Answer 14

the whole idea is about regulation since having permitivity will allow for membrane to stop and let molecules come in as seen appropriate

Question 15

could carnitine supplements act as magic pill and promote weight loss

Answer 15

no because translocase protein is saturable meaning if carnitine exceed the threshold then that will cause bottlneck effect and excess carnitine gets ridden of due to body detecting excess carnitine

Question 16

what is the general rule to know how many oxidation rounds the acyl CoA will undergo

Answer 16

number of rounds= n/2 -1 where n is number of carbons

Question 17

what is the overall beta oxidation of 16:0 CoA in mitochondria

Answer 17

that means the chain has only undergone the beta oxidation so:
16:0CoA+7NAD+7FADH+7H2O+7CoA–> 8acetyl CoA+7NADH+7FADH2+7H

Question 17

what are teh 4 steps of beta oxidation

Answer 17

fatty acid oxidation occur at beta carbon which is the third carbon in fatty acid chain:
1- acyl CoA dehydrogenase: produces FADH2 and create double bond in fatty acid chain
2- hydratase comes and add water across teh double bond between B-OH
3- then dehydrogenase produces NADH and creates keto group on B-carbon in chain
4- thiolase will be the last enzyme that uses CoA to release acetyl CoA and produce fatty acyl CoA chain with 2 fewer carbons
each round end up losing 2C from chain

Question 18

what is the summary for fatty acid breakdown

Answer 18

epinephrine and/or glucagon are required for TAG breakdown and teh fatty acids travel in blood by binding to albumin and entering tissues
fatty acids get activated in cytoplasm by acyl CoA synthetase and that requires 2ATP
the carnitine shuttle is responsible for controlling fatty acid entery into matrix in exchange for free carnitine and once in the acyl chains get broken down into beta oxidation to produce acetyl CoA, NADH, and FADH2
so beta oxidation end up producing huge amount of ATP by using the CAC and oxidative phosphorylation

Question 18

what can limit teh CAC from processing the fats product as fuel

Answer 18

CAC use acetyl CoA from fat degradation to egenrate energy but CAC is dependant on the amount of oxaloacetate present so to make efficient ATP from fat, we need oxaloacetate and that moelcule is made from amino acids or pyruvate by enzyme pyruvate carboxylase

Question 19

what are the location of fat metabolism in cell

Answer 19

synthesis of fats occur in cytoplasm and breakdown occur in mitochondria

Question 20

what are teh steps involved in fatty acid synthesis

Answer 20

1- export of the mitochondrial acetyl CoA to cytoplasm for fat synthesis
2- carboxylation of acetyl CoA to malonyl CoA by acetyl CoA carboxylase (ACC)
3- using malonyl CoA to form 16:0 fatty acid chains by fatty acid synthase (FAS)

Question 21

how is the import and export different between beta oxidation and fat synthesis

Answer 21

CoA was teh reason behind aceyl CoA not being able to enter matrix but for fats synthesis citrate is needed and citrate synthase make citrate in CAC and that cna cross membrane when CAC slow down due to having a lot of energy and that citrate is now in cytoplasm and gets broken down into acetyl CoA and also regenertae pyruvate which gets returned to mitochondria while acetyl CoA gets used for synthesis of fatty acyl chains

Question 22

what are teh enzymes needed for acyl chains synthesis

Answer 22

acyl chain synthesis occur in cytoplasm which is where acetyl CoA is and the enzmyes needed are acetyl CoA carboxylase and Fatty Acid Synthase
acetyl CoA carboxylase is responsibvle for convertinf Acetyl CoA to malonyl CoA which is activated 2C carrying precuror for fatty acid synthesis and this enzyme is commited and regulated step for fatty acid synthesis and it uses ATP
Fatty Acid synthase use NADH as reducing power

Question 22

how does acetyl CoA become malonyl CoA and why is malonyl CoA an important molecule

Answer 22

acetyl CoA is carboxylated using ATP to produce malonyl CoA and the presence of CO2 on malonyl make ir the drive for fatty acid synthesis by fatty acid synthase
malonyl CoA is important reciprocal regulation of fats asit allosterically inhibit CAT I to keep the sequence of fatty acid synthesis ON and fatty acid breakdown OFF and preventing futile cycle of synthesizing chains and then breaking them down

Question 23

what are regulations of fat metabolism

Answer 23

acetyl CoA carboxylase is commited step for ATP synthesis
ACC is inhibited by phosphorlyation due to glucagon and epinephrine stimulation and high AMP
insulin and protein phosphotase will activtae ACC by dephosphorylation
citrate can also stimulate while palmitoyl CoA (16:0 CoA) will inhibit ACC
malonyl CoA also shut down fat breakdown by inhibiting carnitine acyltransferase 1

Question 24

summary for fat synthesis

Answer 24

synthesis of fatty acids require action of both acetyl CoA carbocylase and fatty acid synthase
7 cycles of FAS needed to generate 16:0 and involves a 1acetylCoA+1malonylCoA and then 6 malonly CoA molecules for rest of 6 rounds
lot of energy needed for this anabolic pathway as ACC need 7 ATP, 1 for each round, to make teh 7 malonyl CoA and FAS need 14 NADPH
elonagating of 16:0 chain happen in ER by using malonyl CoA and NADPH
desaturases induce cis bonds which require NADPH and oxygen

Question 24

how is acetyl CoA carboxylase (ACC) regulated by phosphorylarion

Answer 24

so ACC is regulated by protein kinase A and phsophotase
active carboxylase will be during anabolic state which is stimulated by insulin and phosphotase has removed that phosphate group on the enzmye
inactive carboxylase is one with phosphate group and that is added by protein kinase A during catabolic state which is stimulated by glucagon and epinephrine

Question 25

how is malonyl used to form fatty acid chain by fatty acid synthase (FAS)

Answer 25

first, the acetyl CoA releases CoA and bind ACP to make acetyl ACP which gets converted to malonyl ACP and from there there are 4 steps:
1- condensation reaction to release CO2and make chain longer by 2C and make an omega carbon
2- redox reaction that uses NADPH
3- dehydration so H2O is released
4- teh second redox reaction that uses NADPH and produce a saturated chain

Question 26

what is biochemical basis of low carb diet and what are teh side affects

Answer 26

low carb= less pyruvate= less acetyl CoA for fatty synthesis by FAS and ACC
since tehre is less pyruvate, that means there is less oxaloacetate to make ATP and if fats are teh only fuel source and in excess, that could increase acetyl CoA and cause ketogenesis and cholestrol synthesis

Question 27

what are the enzymes involved in triglyceride formation

Answer 27

triglycerades are made starting with phosphatitade which is phospholipid and the phosphate gets removed by phosphatase to make diacyglycerol and diaceylglycerol acyltransferase adds third fatty acyl tail to make tri-acyl-glycerol
when there is insulin signalling, indicating anabolic state, this activates all enzymes involved in ACC, FAS, and acyltransferase
so TAGs produced in liver can be released in blood stream as lipoproteins for storage or use

Question 28

describe cholestrol metabolism

Answer 28

involves 30 steps
cholestrol is important for membranes and is metabolized ro prouduce hormones, bile salts, and vit D3
cholestrol is made from acetyl CoA in cytoplasm of liver cells using carbons from fat/prtein/carbohydrate
cholestrol can be modified to hydrophobic, acyl carrying molecules called cholestrol ester by enzyme acyltransferase
producing cholestrol require NADPH and ATP and is regulated by inhibiting enzyme called HMG-CoA reductase

Question 29

what are lipoproteins

Answer 29

they are transport molecules for hydrophobic TAGs and cholestrol esters through teh body
they have thin monolayer of phospholipids and cholestrol
they ahve polar portion facing aqueous exterior and hydrophobic one facing hydrophobic interior
apoproteins are on surface of lipoproteins and are oriented with their hydrophobilic side chains outward abd hydrophobic ones inward

Question 30

describe lipoprotein transporting lipids

Answer 30

lipoproteins are made in liver or intestine and as they travel through body, fatty acids, and cholestrol are transfered to tissues to produce energy, build membranes, or to produce other moelcules
whatever doesn;t get used is returend to liver as lipoprotein remants for rcycling and additional cholestrol or TAG are synthesized for producing new lipoproteins
excess synthesis of fats, defects in receptores, or probelsm with expression and/ or activity of HMG-CoA reductase will disrupt the balance of lipid metabolism and lead to high cholestrol and cardiovascular diseases

Question 31

how are lipoproteins differentiated and what are different types of them

Answer 31

differentiated by their individual components like apoproteins, %TAG, %cholestrol
1- chylomicrons are made in small intestine from diet and are largest and contain apoprotein known as apoportein 48
2- very low density lipoprotein (VLDL)- made by liver and contains ApoB100 protein
lipoprotein ligase attakcs VLDL and hydrolyzes TAGS ro produce IDL and LDL
3- high density lipoprotein (HDL)- good cholestrol that pick up cholestrol and trasnports them back to liver for breakdown and recycling

Question 32

why is HDL a good cholestrol

Answer 32

becuase it travles in body and picks up cholestrol esters using lecithin which is cholestrol acyl transferase (LCAT) enzyme
it returns cholectrol to liver for processing and breakdown

Question 33

relationship between cholestrol and cardiovascular disease

Answer 33

cholestrol is found in diet but it is also synthesized in liver
liver is responsible for monitoring cholestrol levels for lipoprotein recycling and synthesis of new cholestrol
increased cholestrol intake and synthesis in liver, or decreased lipid turnover and use will lead to cardiovascular disease
oxidized LDL particles have been found to be prinicipal components in arterial plaques resulting in heart attack or stroke
other types of fats also play role

Question 34

how ti improve cardiovasuclar health

Answer 34

you can’t fight genetics as enzymes and receptores in liver play major role in regulation of cholestrol leverl
excericse and proper diet can help increase HDL and decrease LDL
proper dietrs include monitroing fats intale as it increase trans and saturated fats
stop smokling and decrease stress to lower blodo pressure and prevent arterial damage where oxidized LDL accumulate
last restore should be statin drugs

Question 35

relationship between omega three and cardiovascular health

Answer 35

omegar 3 fatty acids (third carbin having double bond) intake has been associated with reduced VLDL synthesis to prevent plague formation, reduced availibility of FA chains for TAG synthesis, increased phsopholipid synthesis, incresed B-oxidation, and reduced hepatic ACC and FAS enzymes activity