lipids

for oxydation if uneven number of carbons, the vitamin ___ is needed for ___ and vit ___ for ___

-B7 for carboxylase (with also needs bicarbonate and 1ATP) -B12 for L methylmalonyl CoA to succinyl CoA

-cholesterol synthesis takes place in cytosol and SER, where is the transition and which enzyme lies on SER memb? -HMG CoA has two pathways, where do the occure?

-HMG reductase lies on SER and its functional unit is in cytosol, therefore it works in the cytosol but afterwards the reactions take place at the SER -cholesterol pathway at cytosol and then SER and ketone bodies pathway at mit

-oxidation of which co enzyme used to make ceramide? -how many coenzymes are needed? -what is eventually reduced in the process?

-NADPH -> NADP+ (two of them, one for 3keto and one for desaturation) -2, one for reduction of 3 keto sphinganine, another for formation of double bond at C4 -sphinganine backbone is also oxidized, O2 is reduced to two molecules of water

enzymes for FA synthesis complex are? which has thiol group?

-acyl carrier protein, has thiol -acetyl CoA ACP trans acetylase -malonyl CoA ACP transferase -beta ketoacyl ACP synthase (condensing), has thiol -beta ketoacyl ACP reductase -beta hydroxyacyl ACP dehydratase -beta enoyl ACP reductase

zwitterionic phospholipids are?

-also dipole PL -have net charge in physiological PH -PTidyl choline and EM, reason: in 7.4 PH most of amino groups are protonated, need PH of around 9 to be deprotonated. COO- (found in ptidyl serine) on the other hand, is deprotonated at this PH.

dipole phospholipids are?

-also zwitterionic phospholipids -have net charge in physiological PH -PTidyl choline and EM, reason: in 7.4 PH most of amino groups are protonated, need PH of around 9 to be deprotonated. COO- (found in ptidyl serine) on the other hand, is deprotonated at this PH.

uni ionic pospholipids are?

-anions at PH of 7.4 as their alcohol group is not losing hydrogen -ptidyl inositol and ptidyl glycerol

----------------------- fatty acids activation: -by which enzyme? -how much energy does it need? -what are the steps? -how acylCoA then added to glycerol in phospholipid synthesis?

-by acyl-CoA synthetase -ATP --> AMP so in the energy calculations so its as we used 2ATP -two steps for this enzyme: 1. formation of intermediate with FA and AMP (PPi leaves) 2. CoA kickes off AMP to form acylCoA -by acylCoA tranf I, that adds saturated to C1 (forming lyso phosphatidic acid) and acylCoA tranf II, that adds unsaturated to C2

-7 alpha hydroxylase takes place in formation of? -what will the product become?

-catalizes rate limiting step of bile formation -Then formation of conjugated bile acids with COO- group (glycocholic and taurochoilc acids or gly and tauro chenodeoxycholic acids by addition of glycin and taurin) -conjugated bile acid with Na+ or K+ is bile salt

-bile acids are? -their function (if not conjugated)? -why do we need to conjugate some of them? -bile salts are?

-cholesterol containing conjugated acids chiolic and chenodeoxy cholic acids (with COO- and taurin or glycin groups) *bile acids found in the bile which emulsifies and act to break up fats in the small intestine into miscells and therefore increase the fat's surface area *have OH on C7 and sometimes on C12 (C12 in cholic acids and not in chenocholic acids) -function to excrete cholesterol via feces and urine -conjugated have lower Pka so they become deprotonated and better help in emulsification -salts are bile acid with Na+ or K+

regulation of fatty acid synthesis? what is inhibiting the opposite pathway (B oxidation)?

-citrate lyase - positive by insulin -inhibition of acetyl CoA carboxylase by glucagon, epin and palmitoyl CoA *CAT 1 - negative by malonyl CoA

farnestyl can be precursor of what (in addition to cholesterol)?

-dolichol -beta carothen -ubiquinone

Sphingomyelin are made of which head group? what is the charge?

-either phosphatidylcholine or phosphatidylethanolamine -its head groups have no charge

-Platelet Activating Factor (PAF) features -it is more/less soluble then plasmalogen, why?

-ether glycerophospholipids in which the alkyl chain is saturated and acetyl is attached, have choline as head group -more, has ester bond in C2 remember: acetyl choline

Plasmalogens structures? begins to be synthesized from the molecule ____ and the organelle ____ and finishes at ____

-ether glycerophospholipids in which the alkyl chain is unsaturated and ethanolamine as head group -made from DHAP at peroxysome and later in ER remember: DoublE (DoubleEthanolamine, double acyl - two of them)

-the liver can make ketone bodies but can not use them, why? -in which organelle they are formed? -in which organelle they are used? -which organs use them?

-liver lacks beta ketoacyl CoA transferase that forms acetoacatate from acetoacetyl CoA (the enzymes takes CoA from succ-CoA) -mit -mit -heart, brain and muscles use ketone bodies

ketone bodies are needed for which organs?

-needed for heart, brain and muscle -not needed for liver and RBC!!

what happened if FA is odd number of carbons?

-propionyl CoA is made instead of acetyl CoA, which lose 1 ATP by prop CoA carboxylase and additional 2NADH as it becomes succinyl CoA

acetyl-CoA carboxylase: 1. importance 2. structure 3. regulation 4. its product is allosteric regulator where?

-rate limiting step of FA synthesis -has 3 sites: biotin carboxylase (CO2 attaches there), biotin carrier protein (transfer CO2 to other site) and transcarboxylase (gives CO2 to acetyl CoA) -high glucagon makes PKA phosphorylate it, now inactive (opposite fore insulin) גן לאומי קיסריה -malonyl CoA inhibits CAT 1

Deoxycholic acid and lithocholic acid are?

-secondary bile acids -made from cholic acid and chenodeoxy cholic acid respectively by bacterial enzymes -can be conjugated with glycin and taurin (similar to primary bile acids cholic and chenodeoxycholic acids)

which molecule can be classified as "dihydroxy long amino alcohol"? how do this molceule synthesized?

-sphingoid base -cannot be made de novo, made by catabolism of membrane shpingolipids

neutral sphingolipids are? bonds? where?

-type of glycosphingolipids -example: cerebrosides -head groups composed of sugars bonded by glycosidic linkages -found on the outer surface of the plasma membrane

what is special in each of the following: 1. cholesterol oxidase 2. hypoxanthine oxidase 3. dopamine hydroxylase 4. PAA hydroxylase 5. tryp hydroxylase 6. sphingolipid and FA deasturase 7. heme oxygenase 8. squalene epoxidase and cholesterol desmolase

1. 2O2 and 2NADPH (to form isocaproaldehyde) 2. O2 and H2O (makes H2O2) 3. O2 and ascorbate (H2O) 4. O2 and THBP 5. O2 and THBP 6. O2 and NADPH (2H2O) 7. O2 and NADPH (CO) 8. O2 and NADPH (H2O)

what is needed to the following enzymes: 1. acyl Co-A synthetase 2. acyl carriesr protein 3. acetyl CoA carboxylase

1. ATP (that becomes AMP + PPi) 2. pantethine 3. HCO3- and biotin

regarding TAG, DAG and MAG: 1. which have polar group? 2. which is not found in membrane? 3. function of polar group?

1. DAG, MAG (alcohol) 2. TAG as it is non polar 3. make molecule amphipathic

which lipoproteins have APO, what is the function: 1. A1 2. B48 3. B100 4. C2 5. E

1. HDL (activates Lecithin-cholesterol acyltransferase LCAT) 2. chylomicrons (transport) 3. VLDL, IDL, LDL (LDL receptors) 4. HDL, which gives them to chylomicrons and VLDL (for lipoprot lipase) 5. all but LDL (LDL receptors)

1. FA is attached to ____ of sphngolipid by ____ bond 2. polar head group is attached to ____ of sphngolipid by ____ 3. sugar is attached to ____ of sphngolipid by ____ 4. creamide is when ____ is attached to ____ of sphingolipid

1. N group, amide bond 2. C1, phospho diester bond 3. C1, glycosidic bond 4. hydrogen, C2

the following are filled mostly with which molecules: 1. chylomicrons 2. VLDL 3. LDL 4. HDL

1. TAG (almost all) 2. TAG (50%) 3. cholesterol ester (50%) 4. proteins (50%) and cholesterol ester (30%)

the following use which substrates and from which lipoproteins? 1. lipoprot lipase 2. hepatic lipase 3. Lecithin cholesterol acyltransferase LCAT

1. TAG, phospholipids -E is needed, therefore LP chylimic and VLDL 2. TAG, phospholipids -HDL, VLDL, IDL 3. cholesterol and phosphatidylcholin -HDL

in FA synthesis condensation process: 1. ____ is attached to B keto acyl synthase (condensing enzyme) via ___, the transfer is done by ___ 2. ____ is attached to ACP via ___, the transfer is done by ___ 3. in the condensation reaction, CO2 is removed from ___ by ___

1. acetyl CoA, cysteine, ACoA ACP transf 2. malonyl CoA, B5 prosthetic group, MCoA transf 3. malonyl CoA, B keto acyl synthase (condensing enzyme)

two strategies for making phospholipids from phosphatidic acid: 1. in prokaryotes there is only one way and it is? *in this strategy, cardiolipin is formed differently in eukaryotes and prokaryotes, what is the difference? *in this strategy phosphotydil inositol is formed only in ___ cells, PDI acts as a second messenger 2. in eukaryotes there is a way forming ___ that is similar to prokaryotes 3. another strategy for eukaryotes is forming ___ and it is done by?

1. activating phosphatidic acid (CDP DAG) *in prokaryotes, from two phosphitidil glycerol (releasing glycerol) and in some eukaryotes by condensing CDP diacyl glycerol with phosphatydil glycerol (releasing CMP) *eukaryotic 2. anionic (inositol, serine, glycerol) 3. zwitter ionic (EN, choline), by activating head group

regarding unsaturated fatty acids: 1. by which enzyme the double bond is made and what is the limit of this enzyme (and exception)? 2. difference b/w alpha and gamma linolenic acid 3. elongation takes place at ___ and desaturation at ___

1. acyl CoA desaturase, cannot desaturate from delta 10 onwards (cannot form double bond at C12, C15) *the "exception" is formation of double bond at C14 in arachidonic acid but it is a result of elongating the essential FA linolate (9,12) 2. alpha (C9,12,15) is essential while gamma (C6,9,12) is formed from linoleic acid (C9,12) and is needed for arachidonic acid (therefore gamma is not essential but linoleic acid is) 3. mit,ER || ER

in fatty acid oxidation: 1. enzyme special for long fatty acids is? what it the reaction? 2. enzyme special for branched FA is?

1. acyl CoA oxidase (peroxisome) acylCoA + O2 -> tr2enoylCoA +H2O2 2. alpha hydroxylase (peroxisome)

for phospholipids: 1. ethanolamine can become ___ 2. choline can become ___ 3. serine can become ___

1. both 2. none 3. EA

how many co enzymes (and which) are needed in: 1. HMG to mavalonate (explain) 2. mevalonate to isopentyl pyroph. 3. IPP to squalene 4. squalene to lanosterol 5. lanosterol to cholesterol 6. cholesterol to cholesterol ester

1. by HMG reductase, two NADPH are lost for each HMG: two NADH have to be oxidized for two reductions of each HMG (of carboxyl to aldehyde to alcohol) 2. first by phospho mevalonate carboxylase, CO2 leaves and 3 ATP are used for each mevalonate 3. IPP can become dimethyl allyl ppi, together form 10C and then 15C (head-tail condensation) and then two 15C (by head-head) form squalene, in the last step 1NADPH is used 4. 1 NADPH is used 5. 2CO2 and 1 formic acid leaves 6. none *giving a total of: -18 acyl CoA -14 NADPH -18 ATP -8 CO2

regarding phosphotydil inositol 4,5 bisphosphate: 1. on which carbons does the OH group point up and on which down? 2. that cleaves it into two secondary messengers and what are they? 3. the fatty acid on C2 is cleaved by which enzyme? 4. then, the fatty acid on C1 is cleaved by which enzyme?

1. carbons 4,6 down and 1,2,3,5 up 2. phospholipase C (cleaves just before P) into DAG and Ino1,4,5 TP 3. phospho lipase A2 4. lysophospholipase (PLA1 is specific for phosphatidic molecule and not lyso)

the following describe which lipoprotein: 1. formation regulated by insulin 2. exogenous 3. forms in liver only 4. largest 5. forms in intestine and liver 6. use phosphatidylcholine for its ester forming enzyme 7. related to scavanger receptors 8. related to foam cell

1. chylomicrons 2. chylomicrons 3. VLDL 4. chylomicrons 5. HDL 6. HDL (lechitin) 7. HDL (scavenger rec are type of ABC receptors for intake of cholesterol from foam cells) 8. oxoLDL

the following properties are related to which lipoprotein: 1. biggest 2. lease dense 3. endogenous 4. forms in circulation 5. controlled by insulin 6. forms in liver 7. highers amount of proteins 8. highest amount of cholesterol ester 9. highest amount of TAG 10. relatively high amounts of both TAG and chol ester 11. deficiency of its receptor ___ causes hypeTAGemia 12. deficiency of its receptor ___ causes both hyperTAGemia and hypercholemia

1. chylomicrons 2. chylomicrons 3. all but chylmicrons 4. IDL and LDL 5. chylomicrons 6. VLDL and HDL (HDL also in intestine) 7. HDL 8. LDL 9. chylomic and then VLDL 10. IDL 11. apoB48 of chylomicrons and also apoCII of HDL (not gives it to chylomicrons so it is like apoB48 are deficient) 12. apoE of IDL (as it has high amounts of both TAG and chol ester)

phospholipase 1. function 2. takes place at G protein 3. cuts arachidonic acid *which of them cut where?

1. cleaves fatty acids from phospholipids 2. C 3. A2 *A1 cuts ester, C cuts phosphate

Phospholipids synthesis in 2 methods: 1. basis of the metods? 2. which organism? 3. which types of phospjholipids are mainly made in each method?

1. cytosine di phosphate (CDP) attached to DAG 2. mainly prokaryotes (in eukaryotes this method stops before formation of cardiolipin 3. mainly anionic PL (serine, inositolm cardiolipin, glecerol) 1. CDP attached to head group 2. eukaryotes only 3. zwitter ionic PL (choline, EA)

true or false? 1. VLDL is made only in well fed condition 2. tissues that make steroid hormons have more LDL receptors 3. chylomicrons remnants have apoE and B48 only 4. nascent HDL has to react with ABCA1, ABCG1, SRB2 and LDL receptors to get cholesterol and esterify it by LCAT 5. LCAT of HDL forms lyso phosphatidyl choline and adds the FA to cholesterol 6. hepatic lipase hydrolyses CE from VLDL and IDL

1. false, as lipolysis takes place during fasting, it releases free FA until they reach the liver, they can be collected to form VLDL 2. true 3. true 4. false, it would be true without the LDLR 5. true 6. false, hydrolyses TAG from IDL and HDL

glycerol backbone for phospholipid synthesis have different pathways in different organs: 1. liver and kidneys 2. rest of the body

1. glycerol becomes glycerol 3P by glycerol kinase (ATP) 2. DHAP becomes glycerol 3P by G3P DH (NADH)

Pyridoxal phosphate (PLP) is a cofactor for (in carbs and lipids)?

1. glycogen phosporylase 2. serine palmitoyltransferase (first step to make ceramide)

where are the following takes place: 1. fatty acid oxidation 2. acetyl CoA production 3. phospholipid synthesis 4. production of co enzymes needed for FA synthesis (which produced in a pathway that contain shuttle) 5. production of co enzymes needed for FA synthesis (which produced in a pathway that doesn't contain shuttle) 6. ketone body synthesis 7. fatty acid elongation??????? 8. fatty acid synthesis

1. mit matrix and peroxisome 2. mit 3. ER 4. NADPH produced in PPP - cytosol 5. NADPH produced as malate went to pyruvate (malate suttle was needed) - cytosol 6. mit 7. mit and ER?????????? 8. cytosol

which enzymes participates in TAG catabolism?

1. perilipin is phosphorylated by PKA, that coat the surface of the lipid droplet and prevent unneeded lipid mobilization. has role in activation of TAG lipase. 2. hormon sensitive lipase

regarding reducing/non reducing ends, which participates in: 1. connection to ceramide 2. first to be degraded in ganglioside *carbon number ___ of sialic acid will attach to form gangliosides

1. red 2. non red (remember: like in glycogen -reducing first in synthesis -non red first in degradation) *carbon number 2 of sialic acid

what are: 1. stearic acid 2. oleic acid 3. archidonic acid 4. linoleic acid 5. palmitic acid 6. linolenic acid * _____ and _____ cannot be produced. * _____ can produce ____, which can produce ____, all by desaturase.

1. stearic acid - 18 saturated 2. oleic acid - 18 u.s. (9) 3. archidonic acid - 20 u.s (5,8,11,14) 4. linoleic acid - 18 u.s. (9,12) 5. palmitic acid - 16 saturated 6. linolenic acid - 18 u.s. (9,12,15) *linoleic (18:2-9,12) and alpha linolenic (18:3-9,12,15). *linoleic (18:2-9,12) can produce gama linolenic (18:3-6,9,12), which can produce archidonic (20:4-5,8,11,14)

the product of condensation of palmitoyl coA and serine is reduced to form which molecule?

3 ketosphinganine is reduced to form sphinganine

overall reaction of palmitate synthesis

8acetyl CoA + 7ATP +14NADPH + 14H ---> palmitate + 8CoA + 7ADP + 7Pi + 14 NADP + 6H2O

acidic sphingolipid are?

Gangliosides are glycosphingolipids that contain sialic acid (N-acetylneuraminic acid, NANA, Neu5ac) as part of their carbohydrate group and are therefore acidic

-compactin and lovastatin can inhibit what? -they have ____ base incorporated in them

HMG reductase mavalonate

rate-limiting step of cholesterol metabolism

HMG-CoA reductase

2 ketone bodies are? what is the difference in catabolism of them?

acetoacatate and beta hydroxy butyrate *BHB can become acetoacatate by BHB DH and additional NADH is made, so 22.5 ATP from HB and 20 ATP from AA are made.

its possible to know in the exam that a molecule is carnitine if we will see which functional groups?

alcohol, carboxyl and N+ (N with 4 bonds)

the following in catabolism of what? -arylsulfatase -neuroaminidase -hexoaminidase

all in gangliosides catabolism

lipoprotein lipase are?

an enzyme that sits on the outside of cells and breaks apart triglycerides, so that their fatty acids can be removed and taken up by the cell

bile salts are formed in ____ enviorment

basic (alkaline)

what can effect binding of LDL to its receptors

binding is PH dependant: -7.4 - strong binding -4.5-6 weak binding

alpha oxidation - which molecules? where?

break down of branched fatty acids (20C phytanic acid) in peroxisome

carnitine is used to mobily ____, from ___ to ___ by the enzymes ___ and ___

carnitine is used to transfer _acetyl CoA_, from _cytosol_ to _mit matrix_ by the enzymes _carnitine acyl transferase 1_ and _CAT 2_

back bone of glycolipid is?

ceramide

IPP stands for: a. IsoPrene Phosphate b. Isoprene PyroPhosphate c. IsoPentyl Phosphate d. Isopentyl PyroPhosphate *difference b/w IPP and DMAPP?

d. Isopentyl PyroPhosphate *they are isomeres, differe in location of double bond (see picture) total of 4 IPP and 2MDAPP are used for cholesterol

to form secondary bile salts, what is needed to be done by intestinal bacteria enzymes?

deconjugation (remove glucoronic acid or sulphate) and 7 alpha dehydroxylation

degredation of glycosphingolipids begins in ____ by ____ and finishes at ____ by ____

degredation of gangliosides begins in _membrane_ by _sialidase_ and finishes at _lysosomes_ by _lysosomal hydrolase_

what is the mechanism of the last step of the formation of IPP from mavalonate?

dehydration decarboxylation two things need to happen: 1. OH group reacts with ATP which removes OH by dehydration and breaks into ADP and Pi 2. decarbxylation

steps of fat digestion

duodenum: 1. bile arrives and emulsifies the fat 2. lipase breaks TAG to FA duodenum and intestine: 3. in mucosa of enterocytes and SER, TAGs are formed again 4. TAG, chol esters and apoB48 (RER and golgi) forms chylomic and transported to lymph and blood blood: 5. LPL in endothilium releases some FA and glycerol from TAG, then goes to liver and other lipoproteins are made

phosphotidyl-inositol function

fatty acids attach to membrane, inositol is attached to membrane protein to anchor them

which molecule is responsible for blood type?

glycosphingolipid -in A type - terminal carbohydrate is N acetyl Gala amine

synthesis of which lipids takes place at golgi?

glycosphingolipids and gangliosides

omega oxidation - where? which molecules undergo it? what it yields?

happens in the SER, creates dicarboxylic acids from a 10/12 C fatty acid and used if there is a defect in B oxidation enzymes -in this process the FA is hydroxylated (alcohol added to last C) and twice dehydrogenated (alcohol to carboxyl), yields succinate and adipate

in B oxidation, ___ is inhibited by too much NADH and ___ is inhibited by too much acetyl CoA

hydroxyacylCoA DH, thiolase

what is the relation b\w ketone bodies and diabetes

increased in diabetes

what is the relation between insulin and fatty acids

insulin stimulates glycolysis (more acetyl CoA) and therefore, fatty acid synthesis from acetyl CoA

why doesn't the liver oxidize ketone bodies?

lack beta keto acyl transferase (adds acetyl coa to acetoacatate), found only in extra hepatic tissue

Elongases and Desaturases are?

make longer chain fatty acids and create double bonds in unsaturated fatty acids -elongases in ER and mit -desaturases in ER

7 alpha hydroxylase is bile acid rate limiting enzyme which needes ___, ___ and ___ to work

molecular oxygen, heme containing enzyme P450 , vit c and NADPH

what happen if FA is unsaturated (one double bond)? what is the result?

need to isomerase the molecule into trans double bond b\w C2 and C3 (instead of cis b\w C3 and C4) *no need for oxydation so 1 FADH2 is not produced

what happen if FA is unsaturated (two double bonds)? what is the result?

need to isomerase the molecule into trans double bond b\w C2 and C3 (instead of cis b\w C3 and C4) -then reduce the molecule into 1 doule bond b\w C3 and C4, 1 NADH is needed -then isomerase the molecule again into trans double bond b\w C2 and C3 (instead of cis b\w C3 and C4), now there is no need for oxydation so in addition, 1 FADH2 is not produced

sphingolipids are made by condensation of?

palmitoyl coA and serine

Eicosanoids function and types? which are affected by aspirin?

paracrine molecules, with primary functions in the inflammatory response 1. prostaglandins 2. thromoxane 3. leukotriene note: specific make only 1 and 2 cyclic, therefore can be inhibited by aspirin

conjugation of 7hydroxy chol to form bile acids takes place in which organelle?

peroxisome

bacteria and humans share a common strategy for making phospholipids. even though, the bacteria keep this mechanism until formation of cardiolipin and humans stop at the level of ____

phosphotidyl glycerol,

3 Eicosanoids are?

prostaglandins, leukotrienes, thromboxanes

LCAT and ACAT locations

remember: A not A, L not L LCAT - plAsma ACAT - Liver

separation of lipoproteins by electrophoresis and centrifuge

similar result in both separations

The core of _____ is the long-chain amino alcohol called _____

sphingolipid, sphingosine

what is the reason for omega 3 and 6 to be essential and not omega 9?

the body can make a double bond at C9 ( 16C palmitate to 18C stearate to unsaturated 18C olate) while only plants can make linolate from olate and alpha linolenate (9,12,15) from linolate however body can make gamma linolanate (6,9,12) from linolate and arachidonic from the gamma

lysophosphatidic acid is?

type of MAG with phosphate on C3