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11.

1 Lipid and Amino Acid Metabolism


Lipid Digestion and Absorption
o Mechanical digestion of lipids occurs primarily in the stomach.
o Chemical digestion of lipids occurs in the small intestine and is facilitated by bile,
pancreatic lipase, colipase, and cholesterol esterase.
o Digested lipids may form micelles for absorption or be absorbed directly
o Short chain fatty acids are absorbed across the intestine into the blood
o Long chain fatty acids are absorbed as micelles and assembled into Chylomicrons for
release into the lymphatic system.
Chylomicrons are synthesis in E.R. and Package in the Golgi apparatus
Exits through Basolateral membrane via exocytosis and enters to lacteal
---> to thoracic duct ---> blood stream.

11.2 Lipid Mobilization

o Lipids are mobilized from adipocytes by hormone-sensitive lipase.


o Lipids are mobilized from lipoproteins by lipoprotein lipase.
11.3 Lipid Transport
o Chylomicrons= are transport mechanism for dietary triacylglycerol molecules and are
transported via the lymphatic system.
o VLDL= transports newly synthesized triacylglycerol molecules from the liver to
peripheral tissues in the bloodstream.
o IDL= in transition between triacylglycerol and cholesterol transport; it picks up
cholesteryl esters from HDL.
o LDL= primarily transport cholesterol for use by tissues
o HDL= is involved in the reverse transport of cholesterol
o Apoproteins= control interactions between lipoproteins.

11.4 Cholesterol Metabolism


o Cholesterol may be obtained through dietary sources or through de novo synthesis in the
liver.
o The key enzymes in cholesterol biosynthesis is HMG-CoA reductase.
o LCAT catalyzes the formation of cholesteryl ester for transport with HDL
o CETP catalyzes the transition of IDL to LDL by transferring cholesteryl ester from HDL.
11.5 Fatty Acids and Triacylglycerols

o When the ATP levels are high, than the Electron Transport Chain is inhibited. This will
reduce amount of NADH is used and causes an increase in NADH.
o Both high levels of NADH and ATP stop the Critic Acid Cycle, which stop using AcetylCoA. This allows an abundance of Acetyl-CoA build up in the mitochondria.

Palmitate synthesis

o High insulin levels causes an increase of Acetyl-CoA Carboxylase and Fatty Acid
Synthase (FAS).
o This reaction is an endogenic.

o The decarboxylation of Malonyl-CoA repeats until the desires number of fatty acid is
reach.
o Malonyl-CoA is being decarboxylation and the Acetyl group is begin reduced, from this
process these two molecules is combined together.
Palmitate Oxidation

o 14-20 fatty acid are hard to get into the Mitochondrial Matrix.
o This process depends on the concentration in the blood and will not go under low
concentration.
o Also, Malonyl-CoA can inhibition the Carnitine Transporter, which prevents the Betaoxidation.

Oxidation of Polyunsaturated Fatty Acids

Beta Oxidation Summary:


o Removes 2 Carbon at a time.
o Even # chains: 1 acetyl CoA; 2 carbons in chain.
o odd# chains: last 3 carbons produce pyruvate.
o Poly-saturated Chains: special enzymes required.
11.6: Ketone Bodies
Ketogenesis
o Ketogenesis occurs in the mitochondria of livers cells, when excess acetyl-CoA
accumulates in the fasting state.
o HMG-CoA synthase forms HMG-CoA, and HMG-CoA lyase breaks down HNG-CoA
into acetoacetate (NADH---> NAD+) , which is reduced to 3-hydroxybutyrate. Acetone
is the minor product that is formed but will not be used as energy.

Ketolysis
o Acetoacetate picked up form the blood is activated in the mitochondria by succinyl-CoA
acetoacetyl-CoA transferase (Thiophorase), an enzyme present only in tissue outside the
liver. During this reaction 3-hydroxybutyrate us oxidized to acetoacetate. The liver lacks
this enzyme, so it can't catabolize the ketone bodies that is produces.

o Ketolysis occurs in muscle, Renal Cortex, and Brian( if prolonged Fast).

Ketolysis in the Brian


o During a prolonged fast, the brains begins to derive up to two-third of its energy from
ketone bodies.
o When the Ketones are metabolized to acetyl-CoA, pyruvate dehydrogenase is inhibited.
Glycolsis and glucose uptake in the brain decrease. This spares the protein in the body,
which otherwise would be catabolized to form glucose by gluconeogenesis in the liver,
and allows the brain to indirectly metabolize fatty acids as ketone bodies.

11.7 Protein Catabolism


Protein Digestion
o Proteins enters in the stomach , where pepsinogen is activated by the HCl to pepsin.
o Pepsin Cleaves polypeptide chains into smaller fragments.
o The smaller fragments then travel to the small intense and are further cleave.(Pancreatic
Proteases cleave polypeptides at specific residues).
Trypsinogen ---> trypsin
Chymotrypsinogen ----> Chymotrypsin
pro-carboxpeptidase B----> carboxpeptidase B
pro-carboxypeptidase A---> carboxypeptidase A
o The small amino acid then travels to small intense brush-border.
Brush-border enzymes :( dipeptidase and aminopeptidase)
these enzymes are broke into amino acid, dipeptides, and
aminopeptidase.'

Protein Absorption
o Absorption in Small Intestine ( the lumen)
The amino acids cross the intestine lumen through active transport (Na+).
sodium are pump into the cell and protons are pump out.
At the basal membrane amino acids undergoes simple diffusion into the
blood stream. However, dipeptides and tripeptides undergoes facilitated
diffusion (H+)
Protein As Energy
In Fasting State
o When other energy sources are low, furthermore, protein can be used for energy.
o De-amination and transamination involves the process of removing amino group from the
carbon backbone.
Glucogenic vs. Ketogenic
Glucogenic (Glucogenic amino acids---> glucose---> glycolysis)
o serine
o glycine
o alanine
o arginine
o histidine
o glutamine
o methionine
o asparagine
o glutamate
o aspartate
o cysteine
o proline
o valine
Ketogenic (Ketogenic amino acids ---> acetyl-CoA---> Citric acid cycle)
o Leucine
o Lysine
Both
o
o
o
o
o

Threonine
isoleucine
phenylalanine
tryptophan
tryosine

The L amino acids are ketogenic


The PhIT amino acids fit into both categories
Waste Disposal
o Ammonium travel though the blood stream into the liver. Where then enters the Urea
cycle. (Don't not to know the intermediates for this cycle on the MCAT).
o Just know that ammonium and basic amino acid side chain goes into the urea cycle and
undergoes chemical reaction to produce urea.