concept 1d part2 Flashcards
dietary fat
consists mainly of triacylglycerols
remained comprised of cholesterol, cholesterol esters, phospholipids, and free fatty acids
lipid digestion
minimal in mouth and stomach
transported to the small intestines essentially intact where emulsification occurs
then pancreas secretes enzymes into the small intestine
these enzymes hydrolyze lipid components to 2-monoacylglycerol, free fatty acids, and cholesterol
emulsification
mixing of 2 normally immiscible liquids (for lipids its fat and water)
formation of emulsion increases surface area of lipid leading to greater enzymatic interactions and processing
aided by bile
bile
contains bile salts, pigments, and cholesterol
secreted by the liver and stored in the gallbladder
aids in emulsification
pancreatic secretions
pancreatic lipase, colipase, and cholesterol esterase
secreted into the small intestine to hydrolyze lipid components to 2-monoacylglycerol, free fatty acids, and cholesterol
micelles
clusters of amphipathic lipids that are soluble in the aqueous environment of intestinal lumen
water-soluble spheres w/ a lipid-soluble interior
vital in digestion, transport, and absorption of lipid-soluble substance from duodenum to ileum
formed by free fatty acids, cholesterol, 2-monoacylglycerol, and bile salts
structure of micelles
collections of lipids with their hydrophobic ends oriented toward center and charged ends oriented toward the aqueous environment
collect lipids within their hydrophobic center
absorption
micelles diffuse to brush border of intestinal mucosal cells and are absorbed
digested lipids pass through the brush border , where they are absorbed into the mucosa and re-esterified to form triacylglycerols and cholesterol esters and packaged
more water-soluble short-chain fatty acids absorbed by simple diffusion directly to bloodstream
chylomicrons
packed triacylglycerols and cholesterol lipids after absorption
along with apoproteins, fat-soluble vitamins, and other lipids
pathway of chylomicrons
leave the intestine via lacteals, the vessels of the lymphatic system
re-enter the bloodstream via the thoracic duct, a long lymphatic vessel that empties into the left subclavian vein at the base of the neck
postabsorptive state
at night
utilizing energy stores instead of food for fuel
fatty acids are released from adipose tissue and used for energy
decreased insulin, increased epinephrine, increased cortisol
hormone-sensitive lipase (HSL)
activated by decreased insulin
hydrolyzes triacylglycerols yielding fatty acids and glycerol
also activated by epinephrine and cortisol
mobilization of triacylglycerols
hydrolyzed in adipose tissue to glycerol and fatty acids then transported to the liver
glycerol participates in glycolysis or gluconeogenesis to form glucose
fatty acids undergo beta-oxidation to form acetyl-CoA for the citric acid cycle and ketone bodies
lipoprotein lipase (LPL)
necessary for the metabolism of chylomicrons and very-low-density lipoproteins
enzyme that can release free fatty acids from triacylglycerols in lipoproteins
free fatty acid transport
transported through the blood in association with albumin, a carrier protein
lipoprotein
transport mechanism for lipids within the circulatory and lymphatic systems
include chylomicrons and VLDL which transport triacylglycerols
HDL, IDL, and LDL which transport cholesterol and cholesteryl esters
structure of lipoproteins
phospholipid sphere with hydrophilic tail on inside and hydrophobic tail pointing out
cholesterol in the membrane
triacylglycerol (lipids) on the inside of the sphere
apoprotein B-100 spanning the membrane
types of lipoproteins
chylomicrons (least dense) very-low-density lipoproteins (VLDL) intermediate-density lipoproteins (IDL) low-density lipoproteins (LDL) high-density lipoproteins (HDL) (most dense)
chylomicrons
transport dietary triacylglycerols and cholesterol from intestines to tissues
least dense lipoprotein
highly soluble in lymphatic fluid and blood
assembly occurs in intestinal lining, results in nascent chylomicron containing lips and apolipoproteins
very-low-density lipoprotein (VLDL)
transport triacylglycerols from liver to tissues
metabolism similar to chylomicrons
produced and assembled in the liver
also contain fatty acids that are synthesized from excess glucose
intermediate-density lipoprotein (IDL)
picks up cholesterol from HDL to become LDL
picked up by the liver
VLDL with triacylglyceol removed
some processed in the bloodstream
low-density lipoproteins (LDL)
delivers cholesterol into cells
for biosynthesis, cell membranes
bile acids and salts are made from cholesterol in the liver
high-density lipoproteins (HDL)
picks up cholesterol accumulating in blood vessels
delivers cholesterol to liver and steroidogenic tissues
transfers apolipoproteins to other lipoproteins
synthesized in the liver and intestines, released as a dense protein-rick particle in blood
apoproteins
aka apolipoproteins
form of protein component of lipoproteins
receptor molecules and involved in signaling
5 types
types of apoproteins
apoA-I: activates LCAT, enzyme that catalyzes cholesterol esterification
apoB-48: mediates chylomicron secretion
apoB-100: permits uptake of LDL by the liver
apoC-II: activates lipoprotein lipase
apoE: permits uptake o chylomicron remnants and VLDL by the liver
cholesterol
ubiquitous component of all cells in the human body
role in synthesis of cell membranes, steroid hormones, bile acids, and vitamin D
cholesterol sources
most derive it from LDL or HDL
some is synthesized de novo which occurs in the liver and driven by acetyl-CoA and ATP
citrate shuttle
carries mitochondrial acetyl-CoA into the cytoplasm where synthesis occurs
NADPH, from pentose phosphate pathway, supplies reducing equivalents
synthesis of mevalonic acid
in the smooth ER
is the rate-limiting step in the cholesterol biosynthesis
catalyzed by 3-hydroxy-3-methylglutaryl (HMG) CoA reductase
regulation for cholesterol synthesis
increased levels of cholesterol inhibits further synthesis by feedback inhibition mechanism
insulin promotes cholesterol synthesis
control over de novo cholesterol synthesis is dependent on regulation of HGM-CoA reductase gene expression in the cell
specialized enzymes in cholesterol synthesis
lecithin-cholesterol acyltransferase (LCAT)
cholesteryl ester transfer protein (CEPT)
lecithin-cholesterol acyltransferase (LCAT)
enzyme found in the blood stream that is activated by HDL apoproteins
adds a fatty acid to cholesterol
produces soluble cholesteryl esters, in HDL
HDL cholesteryl esters can be distributed to other lipoproteins like LDL
cholesteryl ester transfer protein (CETP)
facilitates the transfer process
HDL cholesteryl esters distributed to IDL, which becomes LDL by acquiring these cholesterol esters from IDL
fatty acids
long-chain carboxylic acids carboxyl carbon is C1 C2 is alpha-carbon found in the body occur as salts capable of forming micelles or esterified to other compounds, membrane lipids
saturated fatty acids
fatty acid with no carbon-carbon double bonds
saturated with Hs
unsaturated fatty acids
fatty acids with carbon-carbon double bonds
have one or more
humans only synthesis a few of these rest are from essential fatty acids in diet
double bonds generally in cis configuration
2 essential fatty acids
alpha-linolenic acid
linoleic acid
poly-unsaturated fatty acids
role in cell membrane fluidity, critical for proper function of cell
omega numbering system
also used for unsaturated fatty acids
designation describes the position of the last double bond relative to the end o the chain
identifies the major precursor fatty acid
synthesis
used as fuel for body and supplied primarily bb diet
excess carbohydrate and protein acquired from diet converted to fatty acids and stored as triacylglycerol for energy
contemplate synthesis, do not rely directly on coding of nucleic acid (lipid and carbohydrate)
fatty acid biosynthesis
occurs in liver
products subsequently transported to adipose tissue for storage
adipose synthesizes small amount
fatty acid biosynthesis enzymes
acetyl-CoA carboxylase
fatty acid synthase
stimulated by insulin
palmitic acid (palmitate)
primary end product of fatty acid synthesis
acetyl-CoA shuttling
acetyl-CoA accumulates in mitochondrial matrix, needs to be moved to the cytosol for fatty acid biosynthesis
Acetyl-CoA is product of PDH complex
couples with oxaloacetyate to form citrate at beginning of citric acid cycle
isocitrate dehydrogenase is rate-limiting, as cell becomes e energetically satisfied, slows the citric acid cycle
causes citrate accumulation, can diffuse across membrane
cytosol citrate lyase splits it back to acetyl-CoA and oxaloacetate
acetyl-CoA carboxylase
activates acetyl-CoA in the cytoplasm for incorporation into fatty acids
rate-limiting enzyme of fatty acid biosynthesis
requires biotin and ATP to function
adds CO2 to acetyl-CoA t po form malonyl-CoA
activated by insulin and citrate
fatty acid synthase
palmitate synthase
palmitte is only fatty acid that humans can synthesize de novo
large multiple enzyme complex
found in cytosol
rapidly induced in the liver following a meal of carbohydrates bc of elevated insulin
acyl carrier protein (ACP)
part of the multienzyme complex, fatty acid synthase
requires pantothenic acid (vitamin B5)
activation of fatty acid synthase
- activation of the growing chain
- activation of malonyl-CoA with ACP
- bond formation b/w these activated molecules
- reduction of a carbonyl to a hydroxyl group
- dehydration, removal of H2O
- reduction to a saturated fatty acid
triacylglycerol synthesis
triglyceride synthesis
formed by attaching three fatty acids (as fatty acyl-CoA) to glycerol
occurs primarily in the liver, and some in adipose tissue
from fatty acids and glycerol 3-phosphate
in liver packaged and sent to adipose tissue as VLD lipoproteins, leaving only small amount of stored triacylglycerols
beta-oxidation
catabolism of most fatty acids
in the mitochondria, peroxisomal beta-oxidation also occurs
alpha-oxidation
catabolism of branched-chain fatty acids
depending on branch points
omega-oxidation
oxidation in which endoplasmic reticulum produces dicarboxylic acids
activation of fatty acid metabolism
first become activated by attachment to CoA
catalyzed by fatty-cyl-CoA synthetase
product is fatty acyl-CoA or acyl-CoA
fatty acid entry into mitochondria
short chain and medium chain fatty acids diffuse freely into mitochondria, where they are oxidized
long chain fatty acids (14-20C) are also oxidized in the mitochondria but require transport via a carnation shuttle
very long-chain fatty acids are oxidized elsewhere
carnitine acyltransferase I
rate-limiting enzyme of fatty acid oxidation
beta-oxidation in mitochondria
reverses the process of fatty acid synthesis by oxidizing and releasing molecules of acetyl-CoA (rather than reducing and linking)
repetition of four steps
process of beta-oxidation
each 4-step cycle accomplishing this releases one acetyl-CoA reduces NAD+ and FAD NADH and FADH2 are oxidized in ETC producing ATP acetyl-CoA is entered into the citric acid cycle (muscles and adipose) or stimulates gluconeogenesis by activating pyruvate carboxylase (liver)
4 steps of beta-oxidation
- oxidation of the fatty acid to form a double bond
- hydration of the double bond to form a hydroxyl group
- splitting of the beta-ketoacid into a shorter acyl-CoA and acetyl-CoA
process continues until the chain has been shorted to 2 carbons, creating final acetyl-CoA
beta-oxidation of odd# fatty acids
undergo beta-oxidation in same manner until final cycle
final step yields one acetyl-CoA and on propionyl-CoA (from 5C fragment)
propionyl-CoA is converted to methylmalonyl-CoA
propionyl-CoA carboxylase
converts propionyl-CoA to methylmalonyl-CoA requires biotin (vitamin B7)
methylmalonyl-CoA
converted into succinyl-CoA catalyzed by methylmalonyl-CoA mutase requires cobalamin (vitamin B12)
succinyl-CoA
a citric acid cycle intermediate
can be converted to malate to enter the gluconeogenic pathway in cytosol
oxidation of unsaturated fatty acids
require 2 additional enzymes bc double bonds can disturb stereochemistry needed for oxidative enzymes to act on fatty acid
catalyzed by enoyl-CoA isomerase
once enough is liberated to isolate the bond within the first 3 carbons
enoyl-CoA isomerase
rearranges cis double bonds at the 3,4 position to trans double bond at the 2,3 position
2,4-dienoyl-CoA reductase
further reduction required for oxidation of polyunsaturated fatty acids
enzyme that is used to convert 2 conjugated double bonds to just one double bond at the 3,4 position
then undergo the same arrangement as monounsaturated fatty acids
ketone bodies
liver converts excess acetyl-CoA from beta-oxidation of fatty acids during fasting state
acetoacetate and 3-hydroxybutyrate
used for energy in various tissues
muscles metabolize ketons as rapidly as liver releases them
this prevents accumulation in bloodstream
after a week of fasting
ketones reach a concentration in the blood that is enough for the brain to begin metabolizing them
known as ketogenesis and ketolysis
ketogenesis
occurs in the mitochondria of liver cells
when excess acetyl-CoA accumulates in fasting state
HMG-CoA synthase forms HMG-CoA
HMG-CoA lyase breaks down HMG-CoA into acetoacetate
which is reduced to 3-hydroxybutyrate
aceton is minor side product and will not be used as energy for tissues
ketolysis
acetoacetate picked up from blood is activated in the mitochondria
catalyzed by succinyl-CoA acetoacetyl-CoA transferase (aka thiophorase)
thiophorase
succinyl-CoA acetoacetyl-CoA transferase
enzyme in tissues outside the liver
3-hydroxybutyrate is oxidized to acetoacetate
liver cannot catabolized ketone bodies that it produces
protein catabolism
rarely used as energy source but important for other functions
under extreme energy deprivation, can be used for energy
proteins must be digested and absorbed
digestion of proteins
begins in the stomach with pepsin
continues with the pancreatic proteases secreted by zymogens
completed by the small intestine brush-boarder enzymes dipeptidase and amino peptidase
produce of protein digestion
amino acids
dipeptides
tripeptides
aborption of amino acids
and small peptides
through the luminal membrane
accomplished by secondary active transport linked to sodium
at the basal membrane simple and facilitated diffusion transports amino acids into bloodstream
glucogenic amino acids
all but leucine and lysine
can be converted into glucose thought gluconeogenesis
ketogenic amino acids
leucine, lysine, isoleucine, phenylalanine, threonin, tryptophan, and tyrosine
can be converted into acetyl-CoA and ketone bodies
urea cycle
occurs in the liver
body’s primary way of removing excess nitrogen from the body
