Chapter 11- Lipid and Amino Acid Metabolism Flashcards
dietary fat
mainly triacylglyerols
also cholesterol, cholesteryl esters, phospholipids, and free fatty acids.
lipid digestion after intake
gets to the small intestine without being broken down much at all. in the duodenum they are emulsified which creates a larger surface area of the lipid
lipid emulsification
mixing of two normally immiscible liquids, in this case fat and water. aided by bile (contains bile salts, pigments, and cholesterol)
bile
secreted by liver and stored in gallbladder
pancreas and lipid digestion
pancreas secretes pancreatic lipase, colipase, and cholesterol esterase into the small intestine. these enzymes hydrolyze the lipid componenets to 2-monoacylglycerol, free fatty acids, and cholesterol.
during lipid digestion there is micelle formation…explain.
micelles are clusters of amphipathic lipids that are soluble in the aqueous environment of the intestinal lumen. formed at duodenum and travel all the way down to the ileum. at the end of the ileum bile salts are reabsorbed and recycled. any fat that remind will pass into the large intestine and will be in stool.
lipid absorption
micelles diffuse to the brush border of the intestinal mucosal cells where they are absorbed into the mucosa and re-esterfied to form triacylglycerols and cholesteryl esters and packaged, along with certain apoproteins, fat-soluble vitamins, and other lipids, into chylomicrons.
chylomicrons leave intestine via lacteals (vessels of lymphatic system) and re-enter the bloodstream via the thoracic duct (long lymphatic vessel that empties into the left subclavian vein at the base of the neck)
*note: more water soluble short chain fatty acids can be absorbed by simple diffusion directly into the bloodstream.
what does a fall in insulin levels activate?
hormone-sensitive lipase (HSL, effective in adipose cells), which hydrolyzes triacylglycerols- yielding fatty acids and glycerol. once released it may be transported to liver for glycolysis or gluconeogenesis.
- HSL can also be activated by epinephrine and cortisol.
lipoprotein lipase (LPL)
necessary for metabolism of chylomicrons and very-low-density lipoproteins (VLDL). LPL is an enzyme that can release free fatty acids from triacylglycerols in these lipoproteins.
albumin
carrier protein that transports free fatty acids through the blood
how are triacylclycerol and cholesterol transported in the blood?
as lipoproteins: aggregates of apolipoproteins and lipids. (named according to their protein density)
ex: chylomicros (least dense, highest fat to protein ratio)
VLDL, very low density lipoprotein (slightly more dense)
IDL, intermediate density
LDL, low desnity
HDL, high density
Chylomicrons
transport dietyary triacylglycerols and cholesterol as micelles from intestine to tissues
highly soluble in lymphatic fluid and blood.
assembly occurs in intestinal lining.
VLDL
transports triacylglycerols from liver to tissues
similar function to chylomicrons but produced and assembled in liver cells.
contain fatty acids that are synthesized from excess glucose or chylomicron remnants.
IDL (aka. VLDL remnants)
picks up cholesterol from HDL to become LDL. formed when a triacylglycerol is removed from VLDL.
some is absorbed with liver apolipoproteins and some is processed in bloodstream.
IDL exists as a transition particle between triacylglycerol transport (associated with chylomicrons and VLDL) and cholesterol transport (associated with LDL and HDL)
LDL
NOT healthy cholesterol: delivers cholesterol into cells.
majority of cholesterol measured in blood is LDL.
HDL
HEALTHY CHOLESTEROL: picks up cholesterol accumulating in blood vessels. Delivers cholesterol to liver and steroidogenic tissues.
synthesized in liver and intestines and released as dense, protein rich particles into the blood.
contains apolipoproteins that clean up excess cholesterol from blood vessels for excretion.
apolipoproteins (aka. apoproteins)
form the protein component of the lipoproteins. receport molecules and are involved in signaling
ex: apoE- permits uptake of chylomicron remnants and VLDL by the liver
cholesterol
plays major role in synthesis of cell membranes, steroid hormones, bile acids, and vitamin D.
De novo synthesis of cholesterol
de novo: occuring from the beginning.
occurs in the liver and is driven by acetyl-CoA and ATP
citrate shuttle, carries mitochondrial acetyl-CoA into cytoplasm. then mevalonic acid is synthesized in the smooth ER (rate-limiting step). then cholesterol is formed via 3-hydroxy-3-methylglutaryl (HMG) CoA reductase.
cholesterol synthesis regulation
- high levels of cholesterol inhibit formation
- insulin promotes cholesterol synthesis
- control over de novo cholesterol synthesis is also dependent on regulation of HMG-CoA reductase gene expression in the cell.
2 enzymes involved in cholesterol transportation
- LCAT
2. CETP
Lecithin-cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP)
enzyme found in the bloodstream that is activated by HDL apoproteins. Adds fatty acid to cholesterol (producing cholesteryl esters, like the ones in HDL.
*LCAT catalyzes esterfication of cholesterol to form cholesteryl esters. CETP promotes transfer of cholestryl esters from HDL to IDL, forming LDL.
fatty acids
long-chain carboxylic acids. carboxyl carbon is carbon 1 and carbon 2 is referred to as the alpha-carbon.
2 important, essential fatty acids
- a-linolenic acid
- linoleic acid
* both polyunsaturated fatty acids as well as other acids are formed and help maintain membrane fluidity which is critical for proper functioning of the cell.
nomenclature of fatty acids
carbons: double bonds
omega (w) numbering system used for unsaturated fatty acids. w- describes the position of the last double bond relative to the end of the chain and identifies the major precursor fatty acid.
nontemplate synthesis
do not rely directly on coding of nucleic acid
ex: lipid and carbohydrate synthesis
fatty acid biosynthesis
humans can only synthesize one fatty acid (palmitic acid—-16:0)
occurs in liver. essentially activation followed by bond formation, reduction, dehydration, and reduction.
products transported to adipose tissue for storage
primary end product: palmitic acid (palmitate)
2 major enzymes in fatty acid synthesis
acetyl-CoA carboxylase and fatty acid synthase
*both stimulated by insulin
what happens after a large meal?
acetyl-CoA accumulates in the mitochondrial matrix and needs to be moved to the cytosol for fatty acid biosynthesis.
citrate lyase
splits citrate into acetyl-CoA and oxaloacetate
acetyl-CoA carboxylase
it adds CO2 to acetyl-CoA to form malonyl-CoA (this is removed later by fatty acid synthase during fatty acid production)
activated by insulin and citrate
requires biotin and ATP to function
fatty acid synthase
aka. palmitate synthase b/c palmitate is the only fatty acid that humans can synthesize de novo.
large multienzyme complex in cytosol that is rapidly induced in liver following a high carb meal due to elevated insulin.
what is the opposite of fatty acid synthesis?
B-oxidation—> oxidizing and releasing molecules of acetyl-CoA
*both invovle transport across the mitochondrial membrane, followed by a series of redox reactions, but always in opposite directions to one another.
where does B-oxidation occur
mitochondria, but peroxisomal B-oxidation also occurs.
what inhibits and stimulates the B-oxidation process?
inhibited by: B-oxidation (indirectly)
stimulated by: insulin
B-oxidation: activation
fatty acid metabolism starts with attachment to CoA, which is catalyzed by fatty-acyl-CoA synthetase.
how do fatty acids enter the mitochondria
short (2-4C) and medium (6-12C) diffuse freely into mitochondria, where they are oxidized.
long (14-20C) chain fatty acids are oxidized in the mitochondria, but require transport via carnitine shuttle. Carnitine acyltransferase I: rate limiting enzyme of fatty acid oxidation
fatty acids any longer than 20C are oxidized somewhere else in cell.
B-oxidation process
4 steps that cycle and each cycle releases 1 acetyl-CoA while reducing NAD+ and FAD (producing NADH and FADH2)
- oxidation of fatty acid to form a double bond
- hydration of double bond to form a hydroxyl group
- oxidation of hydroxyl group to form a carbonyl (B-ketoacid)
- splitting of the B-ketoacid into a shorter acyl-CoA and acetyl-CoA
*process continues until the chain has been shortened to two carbons, creating a final acetyl-CoA
what does acetyl-CoA do in muscle and adipose tissue?
enters the citric acid cycle
what does acetyl-CoA do in the liver
it stimulates gluconeogenesis by activating pyruvate carboxylase
what happens in a fasting state?
liver produces more acetyl-CoA from B-oxidation than used in the citric acid cycle. much of the acetyl-CoA is used to synthesize ketone bodies (essentially two acetyl-CoA molecules linked together) that are released into the bloodstream and transported to other tissues.
last step of B-oxidation
- for even-chains 2 acetyl-CoA molecules are produced
- for odd-chains it turns into 1 acetyl-CoA and 1 propionyl-CoA. the Propionyl-CoA is converted to methylmalonyl-CoA via propionyl-CoA carboxylase (biotin, B7) and thats converted to succinyl-CoA via methylmalonyl-CoA mutase (B12). succinyl-CoA is then put into the citric acid cycle because its one of the intermediates.
2 extra enzymes are needed when an unsaturated fatty acid is undergoing oxidation
this is because of the double bonds.
FOR MONOUNSATURATED
1. enoyl-CoA isomerase: rearranges cis double bonds to trans
FOR POLYUNSATURATED
2. 2,4-dienoyl-CoA reductase: converts two conjugated double bonds to just one double bond at the 3,4 position
fatty acid synthesis general
synthesized in cytoplasm and modified by enzymes in the smooth endoplasmic reticulum
key concept about ketone bodies
ketone bodies are essentially transportable forms of acetyl-CoA. They are produced by the liver and used by other tissues during prolonged starvation.
acetoacetate and 3-hydroxybutryrate (B-hydroxybutyrate)
2 ketone bodies that the liver converts excess acetyl-CoA into. these can be metabolized in cardiac and skeletal muscle.
ketogenesis
occurs in mitochondria of liver cells when excess acetyl-CoA accumulates in fasting state. (stimulated by fast and excess acetyl-CoA)
HMG-CoA synthase forms HMG-CoA
HMG-CoA lyase breaks down HMG-CoA into acetoacetate, which can then be reduced into 3-hydroxybutyrate (B-ydroxybutyrate)
-acetone is a minor side product, not used for energy
ketolysis
breakdown of ketone bodies to acetyl-CoA for energy.
acetone (a minor side product of ketogenesis) is picked up from blood and activated in mitochondria by succinyl-CoA acetoacetyl-CoA transferase- aka. thiophorase —> enzyme only present in tissues outside of liver.
ketolysis in brain
- prolonged fast (more than 1 week)
- brain gets 2/3 of energy from ketone bodies
- ketones in brain cause pyruvate dehydrogenase to be inhibited in brain (stops brain from using up proteins in body)
key concept about metabolism
directed toward conserving tissues to the greatest extent possible, especially the brain and heart. digestion of protein compromises muscle–potentially that of the heart– so it is unlikely to occur under normal conditions.
protein catabolism
only occurs under extreme energy deprivation. can result in serious illness.
where does digestion of protein begin and with what?
begins in stomach with pepsin and continues with pancreatic proteases (trypsin, chymotrypsin, and carboxypeptidases A and B, all of which are secreted by zymogens)
what are where are the enzymes that complete protein digestion?
small intestinal brush-boarder enzymes dipeptidase and aminopeptidase.
main end products of protein digestion and what happens happens to them
amino acids, dipeptides, tripeptides
absorption of these through the luminal membrane is accomplished by secondary active transport linked to Na+ then through simple and facilitated diffusion to the bloodstream
where does protein catabolism occur
muscle and liver.
transamination and deamination
amino acids released from proteins usually lose their amino group through these (then goes into urea cycle for safe excretion). the remaining carbon skeleton can be used for energy.
two types of amino acids (based on ability to turn into specific metabolic intermediates)
- glucogenic (all but leucine and lysine)- converted to glucose
- ketogenic (leucine and lysine)- converted to acetyl-CoA and ketone bodies
urea cycle
occurs in liver and is body’s primary way of removing excess nitrogen from the body.
