Lipid & Amino Acid Metabolism Flashcards
Where does mechanical digestion of lipids primarily occur?
mouth and stomach
What facilitates chemical digestion of lipids in the small intestine?
- bile
- pancreatic lipase
- colipase
- cholesterol esterase
How are short-chain fatty acids absorbed?
absorbed across the intestine into the blood via simple diffusion
How are long-chain fatty acids absorbed?
absorbed as micelles and assembled into chylomicrons for release into the lymphatic system
Micelles
- collections of lipids with their hydrophobic ends oriented toward the center and their changed ends oriented toward the aqueous environment
- collect lipids within their hydrophobic centers
- water-soluble
Hormone-Sensitive Lipase
- activated by a fall in insulin levels
- hydrolyzes triacylglycerols, yielding fatty acids and glycerol
- effective within adipose cells
Lipoprotein Lipase
- necessary for metabolism of chylomicrons and very-low-density liporpoteins
- enzyme that can release free fatty acids from triacylglycerols in lipoproteins
What is the ration of free fatty acids to glycerol?
3:1
What are free fatty acids associated with as they are transported through the blood?
albumin (carrier protein)
Lipoproteins
- aggregates of apolipoproteins and lipids
- transport triacylglycerol and cholesterol in the blood
Chylomicrons
- least dense
- highest fat-to-protein ratio
- transport dietary triacylglycerols, cholesterol, and cholesteryl esters from intestine to tissues
VLDL
- produced and assembled in liver cells
- transports triacylglycerols and fatty acids from liver to tissues
IDL
- intermediate density lipoprotein – VLDL remnants
- picks up cholesteryl esters from HDL to become LDL
- picked up by the liver
- it is a transition state between VLDL and LDL, occurring as the primary lipid within the lipoprotein changes from triacylglycerol to cholesterol
LDL
delivers cholesterol into cells
HDL
- picks up cholesterol accumulating in blood vessels and delivers it to liver and steroidogenic tissues
- transfers apolipoproteins to other lipoproteins
- synthesized in the liver and intestines
Cholesterol
- ubiquitous component of all cells
- plays a major role in synthesis of cell membranes, steroid hormones, bile acids, and vitamin D
Lecithin-Cholesterol Acyltransferase (LCAT)
- specialized enzyme involved in transport of cholesterol
- enzyme found in the bloodstream that is activated by HDL apoproteins
- adds a fatty acid to cholesterol which produces soluble cholesteryl esters
Cholesteryl Ester Transfer Protein (CETP)
enzyme that promotes the transfer of cholesteryl esters from HDL to IDL, forming LDL
Fatty Acid Synthesis
- takes place when there is excess energy to store – excess acetyl-CoA
- occurs in the cytosol of liver cells
- starting materials: acetyl Co-A, malonyl-CoA
Steps of Fatty Acid Synthesis (7):
- Acetyl-CoA Carboxylase adds CO2 to acetyl-CoA to form malonyl-CoA
- attachment of malonyl-CoA to Acyl Carrier Protein (subunit of Fatty Acid Synthase)
- BOND FORMATION between malonyl-ACP and growing fatty acid chain
- REDUCTION of carbonyl group in fatty acid chain to hydroxyl group, while oxidizing NADPH to NADP+
- DEHYDRATION of fatty acid chain
- REDUCTION of double bond in fatty acid chain while oxidizing NADPH to NADP+
- reactions above continue until the 16 carbon palmitate molecule is created
Acetyl-CoA Carboxylase
- rate-limiting enzyme of fatty acid synthesis
- requires biotin and ATP to function
- adds CO2 to acetyl-CoA to form malonyl-CoA
- activated by insulin and citrate
Fatty Acid Synthase
- large multi-enzyme complex found in the cytosol
- rapidly induced in the liver following a meal high in carbs due to increased insulin levels
- contains an acyl carrier protein (ACP) that requires vitamin B5
- requires NADPH
What is the only fatty acid that can be synthesized by the human body?
Palmitic Acid (16:0)
How many Acetyl-CoA groups are required to produce palmitic acid?
8
Beta-Oxidation
- fatty acid catabolism – reverse process of fatty acid synthesis by oxidizing and releasing (rather than reducing and linking)
- occurs in the mitochondria of the liver
- inhibited by insulin
- activated by glucagon
- pathway is a repetition of 4 steps
- each 4 step cycle releases 1 acetyl-CoA and reduces NAD+ to FAD (producing NADH and FADH2)
Steps of Beta-Oxidation:
- OXIDATION of fatty acid to form a double bond, while reducing FAD to FADH2
- HYDRATION of double bond in fatty acid to from a hydroxyl group
- OXIDATION of hydroxyl group to form a carbonyl (beta-ketoacid) while reducing NAD+ to NADH
- SPLITTING of the beta-ketoacid into a shorter acyl-CoA and acetyl-CoA
- process continues until chain has been shortened to two carbons, creating a final acetyl-CoA
What does beta-oxidation of an even-numbered fatty acid yield?
2 acetyl-CoA molecules
What does beta-oxidation of an odd-numbered fatty acid yield?
1 acetyl-CoA and 1 propionyl-CoA (which is eventually converted into succinyl-CoA)
___-___ fatty acids represent an exception to the rule that fatty acids cannot be converted to glucose in humans
odd-carbon
How does beta-oxidation of unsaturated fatty acids differ from that of saturated fatty acids?
there is an additional isomerase (Enoyl-CoA Isomerase) and an additional reductase (2,4-Dienoyl-CoA Reductase) for the beta-oxidation of unsaturated fatty acids, which provide the stereochemistry necessary for further oxidation
Ketone Bodies
- essentially transportable forms of acetyl-CoA
- produced by the liver when it converts excess acetyl-CoA from beta-oxidation of fatty acids into these
- used by other tissues during prolonged starvation
Ketogenesis
- occurs in mitochondria of liver cells when excess acetyl-CoA accumulates in the fasting state
- acetyl-CoA is broken down by HMG-CoA Synthase into HMG-COA which is then broken down by HMG-CoA Lyase into Acetoacetate
- minor side product of this is acetone which can be found in the blood
Ketolysis
- regenerates acetyl-CoA for use as an energy source in peripheral tissues
- acetoacetate picked up from blood is activated in the mitochondria by Succinyl-CoA Acetoacetyl-CoA Transferase to form acetoacetyl-CoA which then turns into 2 acetyl-CoA that can be used in CAC
Can the liver catabolize the ketone bodies that it produces?
No, because it lacks the enzyme Succinyl-CoA Acetoacetyl-CoA Transferase
Proteolysis
- breakdown of proteins
- primarily occurs in the small intestine
Protein Catabolism
- only occurs under conditions of starvation
- results in 3 products: carbon skeleton, amino group, sde chains
What is the fate of the carbon skeleton after protein catabolism?
transport to the liver for processing into glucose or ketone bodies
What is the fate of the amino group after protein catabolism?
feed into the urea cycle for excretion
What is the fate of the side chains after protein catabolism?
- processed depending on their composition
- basic side chains will be processed like amino groups while other functional groups will be treated lie the carbon skeleton
- glucogenic amino acids can be converted into glucose through gluconeogenesis
- ketogenic amino acids can be converted into acetyl-CoA and ketone bodies
What amino acids are ketogenic?
- lysine
- leucine
What amino acids are both ketogenic and glucogenic?
- Tabbys Take Pictures In Turrets*
- Tyrosine
- Tryptophan
- Phenylalanine
- Isoleucine
- Threonine
