lipid and amino acid metabolism flashcards

dietary fat consists of mainly

triaclyglycerols

• remainder: cholesterol, cholesteryl esters, phospholipids, free fatty acids

digestion of lipids in the stomach

duodenum: emulsification, mixing of two normally immiscible liquids

• increases surface area of lipid, allows for greater enzymatic processing

• aided by bile (bile salts, pigments, cholesterol)

pancreas secretes pancreatic lipase, colipase, and cholesterol esterase —> hydrolyzes liquid components

micelle formation after emulsification

• free fatty acids, cholesterol, 2mono-acylglycerol, and bile salts contribute to formation of micelles —> amphipathic lipids soluble spheres

• micells diffuse —> intestinal mucosal cells —> absorbed into mucosa

  • become chylomicrons which leave intestines via lacteals and re enter bloodstream via thoracic duct

what occurs during post absorptive state?

fatty acids are released from adipose tissue and used for energy

• human adipose tissue does not respond directly to glucagon —> fall in insulin levels activates hormone-sensitive lipase

  • hormone-sensitive lipase hydrolyzes triacylglycerols

    • also activated by cortisol and epinephrine

lipoprotein lipase is used to

metabolize chylomicrons and low density lipoproteins

• lipoprotein lipase release fatty acids from lipoprotein

what carries lipids through the blood?

fatty acids: albumin

carrier protein + triacylglycerol + cholesterol are carried as a lipoprotein

• lipoprotein density increases as percentage of protein increases

chylomicrons function

transports dietary triacylglycerols, cholesterol, cholesteryl esters from intestines to tissues

• assembly occurs in intestinal lining

VLDL functions

transports triacylglycerols and fatty acids from liver to tissues

IDL functions

picks up cholesteryl esters from HDL to become LDL; picked up by the liver

• triacylglycerol is removed from VLDL

LDL functions

delivers cholesterol into cells for biosynthesis

• majority of cholesterol measured in blood is associated with LDL

HDL functions

picks up cholesterol accumulating in blood vessels, delivers cholesterol to liver and steroidogenic tissues

• transfers apolipoproteins to other lipoproteins

apolipoprotein descriptions and types (5)

form a protein component of lipoproteins; signaling receptor molecules

1. apoA-I: activates LCAT, enzyme for cholesterol esterification

   1. cholesterol esterfication: allows for transport without toxicity

2. apoB-48: mediates chylomicron secretion

3. apoB-100: permits uptake of LDL by liver

4. apoC-II: activates lipoprotein lipase

5. apoE: permits uptake of chylomicron remnants and VLDL by liver

cholesterol sources and regulation

1. LDL or HDL

2. synthesized in the liver via acetyl coA and ATP

   1. NADPH

   2. rate limiting step: synthesis of mevalonic acid in SER, catalyzed by HMP coA reductase

3. Regulated via:

   1. increased levels of cholesterol

   2. insulin —> promotes cholesterol synthesis

   3. gene expression

specific enzymes involved in the transport of cholesterol (2)

1. Lecithin-cholesterol acyltransferase (LCAT): activated by HDL apoproteins

   1. adds fatty acid to cholesterol, produces esters that are soluble

2. cholesteryl ester transfer protein (CETP): transfer cholesteryl esters to IDL —> LDL

fatty acid nomenclature

carbons: double bonds

alpha linoleic acid and linoleic acid

essential fatty acids, polyunsaturated and important in maintaining cell membrane fluidity

fatty acid biosynthesis

nontemplate synthesis; do not require coding of nucleic acid

• occurs in the liver, products are transported to adipose tissue for storage

• stimulated by insulin

1. Following large meal: acetyl-coA accumulates in mitochondrial matrix, —> moved to cytosol for fatty acid biosynthesis

   1. couples with oxaloacetate —> citrate —> diffuses across mitochondrial membrane

   2. split back by citrate lyase

2. acetyl coA carboxylase —> activates acetyl coA

   1. rate limiting step, requires ATP and biotin to function

   2. activated by insulin and citrate

3. acetyl coA + CO2 —> malonyl coA

4. fatty acid synthase/palmitate synthase

   1. induced in liver after elevated insulin levels

   2. NADPH require to reduce

   3. enzymes in SER elongate and desaturate

triacylglycerol synthesis

storage form of fatty acids: 3 fatty acids + glycerol

• occur in liver and adipose tissue

• liver: triacylglycerols —> adipose tissue as VLDL

peroxisomal beta oxidation

also occurs

fatty acid entry into the mitochondria

short chain and medium chain —> diffuse freely

long chain —> require transport via carnitine shuttle

• carnitine actyltransferase I is rate-limiting enzyme of fatty acid oxidation

beta-oxidation in mitochondria (four steps) and products

• oxidation and releasing molecules of acetyl coA from saturated fatty acid

1. oxidation of fatty acid to form a double bond

2. hydration of double bond to form hydroxyl group

3. oxidation of hydroxyl group to form carbonyl (beta ketoacid)

4. splitting of beta ketoacid into shorter acetyl coA and acetyl coA

products: releases on acetyl-coA, reduces NAD+ and FAD

• it is then oxidized in ETC

• even number chains: yield two acetyl coA

• odd number chains: yield one acetyl coA and other molecule

  • molecule can be converted into glucose; only exception

oxidation of unsaturated fatty acids and polyunsaturated fatty acids

• two additional enzymes are necessary because of double bonds

• enoyl-CoA isomerase —> rearranges cis 3,4 —> trans 2,3

polyunsaturated fatty acids:

• 2,4dienoyl coA reductase converts two conjugated double bonds to just one at the 3,4 cis —> 2,3 trans

how are ketone bodies created

excess acetyl coA from beta-oxidation of fatty acids —> acetoacetate and beta hydroxybutyrate

• cardiac and skeletal muscles use ketone bodies —> convert back to acetyl coA for energy

fasting periods and energy

muscle will metabolize ketones as rapidly as liver releases them; preventing accumulation

• week of fasting: ketones = concentration in blood that is high enough for brain to begin metabolizing them

Ketogenesis and ketolysis methods

ketogenesis occurs in mitochondria of liver cells —> excess acetyl-coA accumulates

• HMG coA synthase —> HMG coA —> HMG lyase —> acetoacetate —> reduced to beta hydroxybutyrate

ketolysis: acetoacetate is activated in the mitochondria by succinyl coA acetoacetyl coA transferase (thiophorase) —> only present in tissues outside the liver

• oxidized to acetylacetyl coA —> liver cannot catabolize ketone bodies

ketolysis in the brain

• prolonged fast —> brain derives 2/3 of energy from ketone bodies

• ketone —> acetyl-coA —> pyruvate dehydrogenase is inhibited, glycolysis and glucose uptake in brain decreases

proteolysis methods and end products

breakdown of proteins, only in extreme energy deprivation

1. pepsin —> trypsin, chymotrypsin, carboxypeptidases A and B ( secreted as zymogens)

2. completed by dipeptidase and aminopeptidase

3. end products: amino acids, dipeptides, tripeptides

   1. luminal membrane: secondary active transport linked to sodium

   2. basal membrane: simple and facilitated diffusion

protein catabolism occurs where?

muscle and liver

glucogenic vs ketogenic amino acids

glucogenic (everything but leucine and lysine): glucose

ketogenic: (leucine and lysine, isoleucine, phenylalanine, threonine, tryptophan, tyrosine): acetyl-coA and ketone bodies

carbon skeleton used as energy source, amino acids are released via transamination