Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Biochemistry > Lipid Metabolism > Flashcards

Lipid Metabolism Flashcards

1
Q

What is the function of fatty acids?

A

metabolic fuel, precursors for eicosanoids, building block for phospholipids and sphingolipids. They are amphpithic. In blood they are boundto albumin and in cells bound to fatty acid binding proteins or as esters of coenzyme A. They are saturated and most commonly exist as cis isomer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the function for triglycerides?

A

storage form and major transport form of fatty acids They are neutral fats and hydrophobic.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the function of ketones?

A

soluble metabolic fuels for skeletal muscle, heart, kidney and brain. Most important are acetoacetate and beta-hydroxybutyrate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the function of cholesterol?

A

structural component of plasma membrane; precursor of steroid hormones, Vitamin D, and bile acids. Contain steroid nucleus. Most cholesterol exists as cholesterol esters

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the function of phospholipids?

A

major building block of membranes; storage site for polyunsaturated fatty acids; component of signal transduction pathways. There are two alcohols that are linked through a phosphate bond.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the function of sphingolipids?

A

structural component of membranes; surface antigens. It has one amino group and two hydroxyl groups. The amino group is linked via an amide bond to a long chain saturated fatty acid and the terminal hydroxyl group can be linked to a variety of compounds.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe digestion in mouth and stomach

A

2 lipases: lingual lipase and gastric lipase

substrate: triglycerides
products: fatty acids and diglycerides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe intestinal digestion.

A

emulsification - bile salts
pancreatic lipase (requires colipase, a small protein for optimal activity)
substrate:triglycerides and diglycerides
products: 2-monoglyceride and fatty acids

cholesteral esterase

substrate: cholesterol esters
product: cholesterol and fatty acids

phospholipidase A2

substrate: phospholipid
product: lysophospholipid and fatty acids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe absorption and reesterification of dietary lipids.

A

Once inside cell, triglycerides and cholesterol esters are reformed, packaged into chylomicrons and secreted into lymphatics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe chylomicron assembly

A

Hydrophobic shell of nascent chylomicron contains apo B48, phospholipid, and unesterified cholesterol. Triglyceride and cholesterol esters are found inside. Most triglycerides are assembled in enterocyte

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe chylomicron secretion

A

Released by exocytosis into lymphatics and carried to thoracic duct where they join at the right atrium to the general circulation. Here they acquire apco C-II and apo-E from HDL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe chylomicron metabolism

A

increases hours after meal and requires 6 to 8 hours to return to basal levels. Contains lipoprotein lipase that hydrolyzes triglycerides in chylomicron. This enzyme requires apo-C for activity. The fatty acids that are released diffuse into tissues to be oxidized or stored

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the conditions that lead to lipid malabsorption?

A

bile salt deficiency
pancreatic enzyme deficiency
defective chylomicron synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the effects of lipid malabsorption?

A

deficiency in fat soluble vitamins: Vit K (clotting), A (nightblindness) D (osteoporosis) E (anemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe the general structure of a lipoprotein

A

consists of a core containing triglycerides and cholesterol esters
has a surface coat containing apoproteins, phospholipids, and unesterified cholesterol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the order based on separation by centrifugation and electrophoresis of the lipoproteins

A

centrifugation (most dense to least): HDL, LDL, VLDL, chylomicrons

electrophoresis (most positive to negative): HDL, VLDL, LDL, chylomicrons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are some of the properties of the lipoproteins?

A

chylomicron- least protein, most triglycerides
VLDL: more lipid than protein but not as much as chylomicron
LDL most cholesterol and cholesterol esters
HDL: most protein, least lipid, least percentage triglyceride, most percentage phospholipid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what is source and function of chylomicrons?

A

source: intestines
function: transport dietary triglycerides to peripheral tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the source and function of VLDLs?

A

source: liver
function: transport triglycerides to peripheral tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the source and function of IDLs?

A

Source: plasma VLDLs
Function: triglyceride transport, precursor of LDL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the source and function of LDLs?

A

Source: plasma IDLs
Function: transport cholesterol to peripheral tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the source and function of HDLs?

A

Source: liver and intestines
Function: reservoir or apoproteins, reverse cholesterol transport

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the major functions of each apoprotein class?

A

Apo A: reverse cholesterol transport
Apo B: Recognition of LDL receptors
Apo C: Regulation of Lipoprotein Lipase
Apo E: Recognition of Remnant receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Describe the exogenous pathway of lipoprotein metabolism.

A

Transport of dietary lipids from the gut to the other tissues as chylomicrons: production of chylomicron remnants that are taken up by the liver.

lipoprotein lipase is bound by GAGs to luminal wall of capillaries especially in adipose, muscle and cardiac tissue. It hydrolyzes triglycerides to fatty acids and glycerol, causing chylomicron to shrink to chylmicron remnants. The synthesis of LPL by adipocytes is stimulated by insulin. The enzyme is activated by Apo C.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Describe the endogenous pathway of lipoprotein metabolism

A

synthesis of VLDL by the liver; metabolism of VLDL to IDL to LDL that are taken up by the liver and other tissues

VLDLs are synthesized only by liver and assembled in ER. The VLDLs transport endogenous lipids (triglycerides and cholesterol esters) from liver to extrahepativ tissues. Only apoprotein on nascent VLDLs is apoB100. Others are attained from HDL in circulation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Describe reverse cholesterol transport pathway

A

Removal of cholesterol from peripheral tissues by HDL; Esterification and transfer to chylomicron remnants and IDL and transport to the liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is the fate of chylomicron remnants?

A

the remnants become smaller, apo C-II is returned to circulating HDLs, leaving apB48 and apo E in surface monolayer. The remnants bind to receptors on liver and are taken up by receptor mediated endocytosis. Apo E binds to remnant receptor, wheras both apo E and apoB48 are required for binding of remnants to LDL receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is the effect of lipoprotein lipase on VLDLs

A

TRiglyceride in VLDLs is hydrolyzed, resulting in progressive shrinking to IDLs. As they become smaller, Apo C-II passed back to HDL, which leaves IDLs that have little affinity for LPL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What is the fate of IDLs?

A

taken up by liver or metabolized by hepatic lipase to LDLs

75% are internalized by liver following interaction of Apo E binding to remnat receptors and apoB-100 to LDL receptors. The more internalized, less in circulation, lower risk of atherosclerosis.

About 25% of the IDLs are converted to LDLs by hepatic lipase, which hydrolyzes both triglycerides and phospholipids. This also results in the return of apo E to the circulating HDL pool

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Describe metabolism of LDL

A

interaction of apoB100 with LDL receptor -> endocytosis. REceptors returned to plasma membrane and endosome fuses with lysosomes, where LDL particle is hydrolyzed. The rates of cholesterol uptake (LDL uptake) and cholesterol synthesis are coordinated by cellular concentration of unesterified cholesterol.

About 75% of plasma LDL cleared by LDL receptor pathway. 25% removed by low affinity receptors known as scavenger receptors found on macrophages. Scavenger receptors have a low affinity for LDL, but a high affinity for oxidized LDL. The synthesis of scavenger receptors, unlike that of LDL receptors, is not regulated by the cellular concentration of cholesterol. As cholesterol accumulates, macrophages are converted to foam cells, which continue to form until they become part of an atherogenic plaque.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Describe the HDL metabolism of reverse cholesterol transport.

A

HDL synthesis occurs mostly in liver, though small amounts in intestinal cells. nascent HDL are disclike, with empty space inside with apo A, C and E on the surface.

HDL serves as circulating respository of apoproteins. Apo C and E exchanged readily, but not A.

The pathway of reverse cholesterol transport results in net transfer of cholesterol from peripheral tissue to liver, where it can be processed for excretion. Pathway is mediated by HDL, although HDL does not carry much cholesterol back to liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What are the four steps in reverse cholesterol transport.

A

Uptake of cholesterol by HDL
Esterification of HDL Cholesterol
Transfer of Cholesterol Esters from HDL to Lipoprotein Remnants
Transfer of HDL cholesterol esters to tissues via scavenger receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Describe uptake of cholesterol by HDL

A

Lipid poor HDL interacts with surface of cells, resulting in translocation of unesterified cholesterol from cell to surface of HDL. Binding HDL to surgace of cells requires A-1. The rate controlling step in reverse cholesterol transfer is transfer of cholesterol and phospholipids from cell to lipid poor HDL, mediated by an ATP-binding cassette transporter (ABCA1)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Describe the esterification of HDL Cholesterol

A

The cholesterol that has been picked up is converted to cholesterol ester by lecithin cholestrol acyl transferase (LCAT) an enzyme in plasma and loosely associated with HDL. Activity of LCAT is stimulated by apo A1. The cholesterol esters formed in this reaction can be transferred either to core of HDL or other lipoprotein remnants.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Describe the transfer of cholesterol esters from HDL to Lipoprotein Remnants

A

IDLs, LDLs and chylomicron remnants have empty space in core created by lipoprotein lipase catalyzed hydrolysis of triglycerides. Cholesterol esters can be transferred into this space in a reaction mediated by cholesterol ester transfer protein (CETP) or apoD. Since remnants contain apo B and apo E, they can be readily cleared by liver, following binding of LDL and remnant receptors. This is indirect pathway of reverse cholesterol transport.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Describe transfer of HDL cholesterol esters to tissues via scavenger receptor B1.

A

HDL binds to scavenger receptor but is not endocytose, cholesterol esters are transferred to cell. Scavenger receptor B1 is expressed on liver, steridogenic tissues, and macrophages in atherosclerotic plaques. This is the direct pathway of the reverse cholesterol transport

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Describe recycling of HDL

A

transfer of cholesterol esters from HDL (steps 3 and 4) regenerate lipid poor HDL, which can reinitiate the cycle by taking up cholesterol and phospholipids from cells

38
Q

What are the courses for the pool of cholesterol in the liver?

A
  1. dietary cholesterol delivered via chylomicron remnants
    de novo synthesis
    extrahepatic tissues cholesterol that is brought to liver by reverse cholesterol transport involving HSL LDL and IDL
39
Q

What are the fates of liver cholesterol?

A

repackaged and secreted in VLDLs
secreted in bile as free cholesterol
converted to bile acids

40
Q

Describe main transport forms for cholesterol.

A

Dietary cholesterol - chylomicrons and chylomicron remnants
endogenous cholesterol - exit liver in VLDLs which become LDLs, which is the major transport form to peripheral tissues. HDL picks it up from peripheral and starts the reverse cholesterol transport

41
Q

what is the energy and reducing power for cholesterol biosynthesis?

A

ATP and NADPH

42
Q

Where does de novo synthesis of cholesterol take place?

A

all nucleated cells

in cytosolic and smooth endoplasmic reticulum

43
Q

What are activated isoprene used for?

A

to synthesize dolichol P, in glycoprotein biosynthesis, coQ, vit A, E, K

44
Q

What is the role of LDL REceptors in regulating cholesterol metabolism?

A

All cells have LDL receptors which are the principal vehicle for transport of cholesterol to peeriphery. LDL is taken up by receptor mediated endocytosis via Apo B100
The free cystolic cholesterol has three effects:
repress synthesis of HMG CoA reductase
repress synthesis of LDL receptors
activates ACAT that forms cholesterol esters for storage

45
Q

What are the major functions of bile acids

A

only significant pathway for cholesterol excretion
prevents precipitation of cholesterol in bile
emulsification of dietary fat
facilitates absorption of fat soluble vitamins

46
Q

Describe the hydroxylation of the ring system

A

Reactions catalyzed by microsomal mixed function oxygenases. These enzymes require molecular oxygen NADPH and cytochrom P450 and then introduce hydroxyl groups into ring in an alpha configuration. The configuration of the hydroyl grou at C3 of cholesterol is altered from the beta to the alpha configuration so that all of the hydroxyl groups project from same side of the ring system
regulation: rate limiting step in the sythesis is hydroxylation at B-7 which is catalyzed by cholesterol 7alpha hydroxylase. This enzyme is inhibited by cholic acid

47
Q

Describe the side chain cleavage reaction

A

A three carbon gragment is cleaved off of the side chain and the terminal carbon is oxidized to carbozylic acid. This reaction also requires a mixed function oxygenase. The major bile acids in humans are cholic acid and chenodeoxylic acid

48
Q

what are the structural properties of bile acids that contribute to lipid emulsification

A

amphipathic nature of the molecule

low pKa of the side chain conjugated group

49
Q

Describe the formation of bile salts

A

the carboxyl group on teh side chain of the bile acids can form amide bonds with either glycine or taurine to form conjugated bile acids. Before the amino acid can be added, the carboxyl group of the bile acid side chain is activated by the reaction with CoA to give high energy thioester. The energy is used to form amid bond. The conjugation improves emulsification properties because pKa of side chain ionizing group is lower than that of original carboxyl group. If the primary bile acid is cholic acid, the conjugated forms are either glycocholic acid or taurocholic acid. If primary bile acid is chenodeoxychoolic acid, the conjugated forms are either glycochenodeoxycholic acid or taurochenodeoxycholic acid

50
Q

describe secondary bile acids

A

they are produced in intestines, by bacterial enzymes which caalze the removal of the 7hydroxy group and conjugated amino acid from the two priary bile acids to produce deoxycholic acid and lithocholic acid

51
Q

Describe the recycling of bile acids between the liver and intestines

A

the enterohepatic circulation - bile salts are the most significant form of cholesterol secretion. Though reabsorption of bile acids and salts is ver efficient. The liver secretes between 15 to 30 grams of bile acid a day with 0.5 g in feces. During digestion, bile acids are released into lumen of the small upper intestin and are reabsorbed by lower small intestin into the portal circulation where they are noncovalently bound to albumin. The process of secretion and reuptake is known as the enterohepatic circulation. One treatment for lowering cholesterol is to increase excretion of bilee acids and salts. This is accomplished by ingested agents that bind bile salts in the GI tract and are excreted in the feces, thus preventing reabsorption.

52
Q

What are the three major pathways of fatty acid metabolism?

A

fatty acid synthesis (liver, sebaceous glands, adipose, lactating mammary glands)
fatty acid storage and mobilization (adipose)
fatty acid oxidation (most tissues)

53
Q

What is the elongation process?

A

synthesis occurs by sequential addition of 2 carbon units to carbozyl end. With the exception of the two carbons at the methyl end, all other carbons are donated by malonyl CoA

54
Q

What is the reductive process of fatty acid synthesis

A

two molecules of NADPH are required for every 2 carbon fragment

55
Q

What is special about palmitic acid?

A

it is the end product in most tissues of fatty acid synthesis, except in lactating mammary, where end product is 10. carbons rather than 16

56
Q

Where does fatty acid synthesis take place?

A

on an acyl carrier protein to which the intermediates are covalently attached by a thioester bond
its in the cytosol but requires participation of the mitochondria because the 2 carbon fragments are generated in the mitochondria

57
Q

What are the stages of Fatty acid synthesis?

A

generation of substrates (acetyl coA, malonyl coa and NADPH)
utilization of substrate to form palmitate
modification of palmitate to give a diverse family of fatty acids

58
Q

What conditions promote fatty acid synthesis?

A

excess glucose and amino acids

stimulated by insulin

59
Q

Describe the citrate shuttle.

A

acetyl coa is formed in the mitochondrial matrix and must be translocated to the cytosol where fatty acid synthesis occurs. Since acetyl coa is impermeable to IMM, it is translocated as citrate

60
Q

What are the sources of NADPH?

A

malic enzyme

pentose phosphate pathway

61
Q

What is the source of malonyl coA

A

it is formed by carboxylation of acetyl coA. It is catalyzed by acetyl CoA carboxylase, a biotin requiring enzyme
Purpose of carboxylation
biotin requirement
primary regulated step in fatty acid synthesis
reaction requires ATP

62
Q

what is the stoichiometry of fatty acid synthesis?

A

acetyl-CoA + 7 Malonyl CoA + 14 NDPH + 14 H+ –> palmitoyl - CoA + 7 CO2 + 7 CoA + 14 NADP+

63
Q

what is the stoichiometry of aceylcoa carboxylase plus fatty acid synthesis?

A

8 acetyl-CoA + 7 ATP + 14 NDPH + 14 H+ –> palmitoyl - CoA + 7 ADP + 7 CoA + 14 NADP+ + 7Pi

64
Q

Describe turnover of triglycerides

A

uptake of fatty acids is followed by conversion to fatty acid CoA. The fatty acids are transferred to C1 and C2 of glycerol 3P to give phosphatidic acid. the phosphate group is removed, resulting in diglycerids. TRansfer of another fatty acdi from fatty acyl coA to 3 OH diglyceride. TRansfer of another fatty acid from fatty acyl CoA to the 3 OH diglyceride results in triglyceride. The glycerol 3P is derived from glucose as an intermediate in glycolysis.

65
Q

why does the glycerol leave the fat cell?

A

because no glycerol kinase in adipose tissue

66
Q

Describe the regulation of the triacylglycerol lipases

A

Under basal conditions, ATGL exists on surface of lipid droplets with low activity and HSL is cytoplasmic. Re-esterification and sythesis of TAGs prevents net lipolysis. Activation of cAMP dependent kinase, from glycerol or epinephine, phosphorlyates HSL and perilipin, resulting in reordering of lipid droplet surface bringing coactivators of ATGL (CGI58) and HSL (Perilipin) together on surface of lipid droplet and increasing the efficiency of lipid hydrolysis to completion with glycerol and fatty acids as the final products. Under stimulated conditions there is no reesterification or synthesis of TAGs allowing net lipolysis.

67
Q

phosphotidylglycerol

A

if phosphoric acid group of a phospholipid is esterified to glycerol, this forms. Its in the mitochondrial membrane

68
Q

cardiolipin

A

esterification of another phophoric acid in phosphotidylglcerol in the three position of glycerol forms this. its found in the mitochondrial membrane

69
Q

functions of phospholipids

A

structural component of membranes
enzyme activation
second messenger signalling (IP3 and DAG produced by phospholipase C on PIP2)
lung functions (surfactant = dipalmtoyl lecition aka dipalmtoyl phosphatidylcholine
detergent function in intestine and gallbladder (components of bile)

70
Q

Conditions that promote fatty acid mobilization from adipose tissue

A

fasting
physical exertion
stress

71
Q

What hormones stimulate fatty acid mobilization?

A

glucagon
epinephrine and acth - physical exertion and stress
glucocorticoids and growth hormone

72
Q

which tissues oxidize fatty acids for energy?

A

all except brain and red blood cells

73
Q

How are free fatty acids transported from adipose to other tissues?

A

more than 99% are bound noncovalently to abumin, which has 3 high affinity sites for fatty acids and several low affinity sites. It can hold on average 0.5 to 1.5 fatty acid molecules are bound per molecule of albumin. less than 1% of the FFAs diffuse across membrane of tissues where they bind to fatty acid binding protein (FABP). equilibrium of bound and unbound FFAs to albumin are constantly readjusted

74
Q

What is the contribution of plasma free fatty acids to daily energy requirement.

A

plasma free fatty acids turn over rapidly. Ther large reserve of albumin bound fatty acids couples with the short half-life results in a turnover of about 200 grams of fatty acids per day. The potential caloric value is about 1900kcal/day

75
Q

What is the function and location of the fatty acid oxidation

A

function: release acetyl CoA and energy in form of electrons to be transfered to NADH and FADH2. Fatty acid oxidation occurs in the mitochondrial matrix.

76
Q

Entry and trappying of fatty acids in the cell

A
  1. binding to FABP

2. Conversion to fatty acyl-coa

77
Q

Describe carnitine shuttle

A

it is used to translocate long chain fatty acyl CoA across the inner mitochondrial membrane. The key enzymes are carnitine acyltransferase I (CAT-I) and carnitine acyltransferase II (CAT-II). Medium and short chain fatty acids can cross the IMM without the carnitine shuttle. Malonyl CoA is an intermediate in fatty acid synthesis and is an inhibitor of CATI.

78
Q

What are the isozymes of fatty acyl coa dehydrogenase?

A

very long chain acyl-CoA DH - C24-C14, C16 optimal
medium chain acyl coA - C14 -C4 (optimal C8)
short chain acyl coA - C6-C4

79
Q

stoichiometry of fatty acid oxidation

A

palmitoyl-coA + 7NAD+ + 7FAD +7CoA+7H2O –> 8 acetyl coA +7FADHs +7NADH +7H+

80
Q

How many molecules of atp would you get from complete oxidation of palmitoyl CoA and palmitic acid

A

palmitoyl coA - 131 ATP

129 ATP

81
Q

describe the regulation of beta-oxidation.

A

the rate of fatty acid oxidation is determined by the availability of fatty acids and the rate at which they enter the mitochondria. The rate limiting step in betaoxidation is catalyzed by CATI (inhibited by malonyl-CoA so betaoxidation and fatty acid synthesis doesn’t occur simultaneously). Since synthesis of malonylCoA is stimulated by insulin, insulin indirectly inhibits fatty acid oxidation by blocking the entry of fatty acids into mitochoncria. The availability of fatty acids as fuels for oxidation is regulated by activity of hormone-sensitive lipase in adipocytes.

82
Q

describe the oxidation of odd-chain fatty acids

A

odd chain fatty acids are oxidized by beta-oxidation. The last cleavage step rtep results in one acetyl coA and propionyl CoA. Propionyl CoA can be converted to succinyl CoA through the action of propionyl CoA carboxylase, an epimerase and methylmalonyl CoA mutase

83
Q

describe the oxidation of unsaturated fatty acids

A

they are oxidized by the pathway of beta-oxidation. However, two auxiliary enzymes are needed to ensure that the double bond is in the righ configuration and is between the alpha and beta carbons. most naturally occuring unsaturated fatty acids are of the cis configuration, wheas the unsaturated intermediate in beta-oxidation is of the trans configuration
enoyl coA isomerase isomerizes the cis double bond in monounsaturated fatty acids to the correct configuration.
2,4 dienoyl CoA reductase is required in the oxidation of PUFAs to ensure that the double bond is between the alpha and beta carbons. Oxidation of PUFAs also requires enoyl CoA isomerase.

84
Q

describe coordination of fatty acid oxidation and fatty acid synthesis

A

allosteric effectors and sites of action: CATI: inhibited by malonyl CoA
Acetyl-CoA Carboxylase: activated by citrate: inhibited by fatty acyl CoA
Hormonal Effects:
Hormone Sensitive Lipase: activated by glucagon (cAMP dependent phosphorylation) makes substrate available for fatty acid oxidation
Acetyl CoA Carboxylase: activated by insulin (promotes dephophorylation)

In liver, activation of ACC and de novo fatty acid synthesis pathway raises the malonylCoA concentration and inhibits fatty acid oxidation, preventing a futile cycle

85
Q

Describe regulation of fatty acid oxidation in muscle

A

non lipogenic tissues such as muscle do not synthesize fatty acids and do not have the fatty acid synthase enzyme. However, acetyl-CoA carboxylase and malonyl-CoA decarboxylase are present. Upon initiation of exercise the AMP-activated protein kinase is rapidly activated. AMPK phosphorylates both ACC and MCD (activating it) thus lowering the concentration of malonyl-CoA, deinhibiting CAT-I and accelerating fatty acid oxidation to provide for the extra energy requirement

86
Q

Describe peroxisomal fatty acid oxidation

A

peroxisomes are important in the oxidation of very long chain fatty acids and branched chain fatty acids.
The oxidation of fatty acids having chain lengths equal or greater than C26 begins in peroxisome and is completed in the mitochondria. The peroxisomal pathway is analogous to the mitochondrial pathway of beta-oxidation, but different isozymes are used and the energy yield is less. The FADH2 formed in the first step of each cycle cannot lead to ATP sythesis, because it is regenerated by O2 with the formation of hydrogen peroxide. When the fatty acids have been reduced to a chain length of C8-C10, they leave the peroxisomes and are taken up by mitochondria, where oxidation is completed

87
Q

Describe branched chain fatty acids:

A

phytanic acid: a saturated fatty acid with methyl groups attached to carbons 3, ,7 ,11, 15
dietary source: vegetables, milk, and fat products derived from ruminants
degraded by alpha-oxidation pathway: cannot undergo beta oxidation because of the beta carbon has a methyl group attached. oxidation starts by hydroxylation of the alpha carbon (catalyzed by alpha hydroxylase. The hydroxylation is followed by decarboxylation resulting in a C19 fatty acid that can be degrade by the beta-oxidation pathway

88
Q

Describe the ketone body metabolism

A

keton boodies are water soluble fuels that are derived from fatty acids. The two ketone bodies are acetoacetate and beta-hydroxybutyrate. They play an important role in fuel homeostasis by providing fuel for muscle and brain during period of fasting and starvation. When circulating concentrations of keton bodies reach 1 to 3 mM they begin to be taken up by eztrahepatic tissues and oxidized. Normally, the concentration of keton bdoes is less than 0.2 mM. After fasting for 3 days, the concentration will be 2 to # mM, and by 3 weeks of fasting, the concentration will be between 7 to 10 mM. Ketons play an important role in the adaption that allows protein to be conserved during starvation. Synthesis occurs in the mitochondria with the enzymes: thiolase, HMG-Coa synthase, HMG CoA lyase, Beta-hydroxybutyrate dehydrogenase

89
Q

Describe the oxidation of ketones,

A

It occurs in extrahepatic tissues (not liver). It occurs in the mitochondria using the following enzymes: beta-hydroxybutyrate dehydrogenase, succinylCoA: acetoacetate-CoA transferase, thiolase

90
Q

Describe diabetic ketoacidosis

A

This insulin deficiency in diabetics leads to the uncontrolled release of fatty acids from adipose tissue, due to the persistent activation of hormone sensitive lipase. Most of these fatty acids are oxidized by the liverm producing more acetyl CoA than the liver needs. The overflow of acetyl-CoA is used for keton synthesis. Levels of ketone bodies as high as 10-20 mM can accumulate in the blood of Type I diabetics, resulting in a type of metabolic acidosis, which if untreated can be fatal. Some of the acetoacetate is spontaneously decarboxylated to acetone, resulting in fruit breath

Biochemistry (7 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions