LIPID METABOLISM By Dr Debalina Basu Dept of
LIPID METABOLISM By Dr. Debalina Basu Dept. of Microbiology Surendranath college
Objectives • To determine the interrelationship between the lipids intake and human physiology • To analyze how different individual and gender react to different amount of intake • To identify the optimal intake to prevent exceeding and shortage of lipids in diet
Why Fatty Acids? (For energy storage? ) • Two reasons: – The carbon in fatty acids (mostly CH 2) is almost completely reduced (so its oxidation yields the most energy possible). – Fatty acids are not hydrated (as mono- and polysaccharides are), so they can pack more closely in storage tissues
Lipids Deficiency • Fat should comprise of 3% of total calories to prevent fatty acid deficiency • Fatty acid deficiency syndromes – Dry scaly skin, dermatitis (Linoleic acid deficiency) – Hand tremors (Prostaglandin deficiency) – Inability to control blood pressure
Lipids Exceeding • Fat should comprise not more than 30% of total calories to prevent lipids exceeding • To prevent overtaking, we should consume fat breakdown (% total calories) – <8% from saturated fat – 10% from polyunsaturated fat – 10 -15% from monounsaturated fat
Introduction • Reserves of stored triglycerides are mobilized as needed for energy production. • Fat mobilization is stimulated by epinephrine. The triglycerides are hydrolyzed to fatty acids and glycerol and enter the blood stream. • Glycerol is converted to glycerol- 3 phosphate and then to dihydroxyacetone phospahte, which enters glycolysis for energy production. • Free fatty acids are converted to fatty acyl Co. A molecules, which are broken down to acetyl Co. A by beta oxidation. The acetyl Co. A may be used for energy production by way of the citric acid cycle and the electron transport chain.
Key Concepts in Lipid Metabolism • Stored lipids is the primary source of energy in most organisms. • The three sources of triacylglycerols in animals are dietary lipids, stored triacylglycerols in adipose tissue, and fatty acids synthesized in the liver. • -oxidation is the mitochondrial process by which fatty acids are oxidized to yield NADH, FADH 2, and acetyl-Co. A. • Ketogenesis takes place in liver mitochondria when acetyl-Co. A levels are high and oxaloacetate levels are low.
Fatty acid are transported into mitochondria by carnitine Carnitine acyltransferase I replaces Co. A with carnitine to form fatty acyl carnitine which is translocated across the inner mitochondrial membrane by the carnitine translocating protein. Lastly, carnitine acyltransferase II release the carnitine and it is shuttled back across the membrane.
Transport into Mitochondria depends on Carnitine + FA~Co. A HS-Co. A Acyl transferase I Carnitine FA~Carnitine N(CH 3)3 CH 2 H-C-OH CH 2 Translocase COOCarnitine FA~Carnitine HS-Co. A FA~Co. A Acyl transferase II
Beta oxidation • The formation of fatty acyl Co. A molecule prepares fatty acids for entry into the mitochondria. Carnitine helps fatty acly Co. A to enter mitochondria. There they are degraded in the catabolic process called beta oxidation. During beta oxidation, the third (or beta) carbon of the saturated fatty acid chain of the fatty acyl Co. A is oxidized to a ketone. • Beta oxidation is a spiral pathway. Each round consists of four enzymecatalyzed steps that yield one molecule of acetyl Co. A and an acyl Co. A shortened by two carbons, which becomes the starting substrate for the next round. Seven rounds of beta oxidation degrade a C 16 fatty acid to eight molecules of acetyl Co. A. Complete oxidation of one molecule of palmitic acid to carbon dioxide and water yields 129 molecules of ATP. One round of beta oxidation yields 17 ATP. Beta Oxidation is regulated by availability of free Co. A, by the ratios of NAD/NADH and Q 2/QH.
-oxidation reactions OXIDATION The -oxidation pathway occurs at the carbon of the fatty acid, thereby releasing the C-1 carboxyl carbon and carbon as the acetate component of acetyl Co. A. HYDRATION OXIDATION THIOLYSIS
One Round (a) and Further Rounds (b) of β-Oxidation EOC Problem 4: explores numbers of round of β-oxidation. EOC Problem 9: Compartmentalization of βoxidation.
Energy Story Part II 1. 0 g glucose = 3. 7 kcal (15. 5 k. J) 1. 0 g stearic acid = 9. 7 kcal (40. 5 k. J) ENERGY CONSERVATION Stearic Acid (C 18 satd) Textbook 9 Acetyl Co. A = 108 ATP (90) 8 FADH 2 = 16 ATP (24) 8 NADH = 24 ATP (20) = 148 ATP (134) - 1 ATP -1 147 ATP (133)
β-Oxidation of Odd Numbered Fatty Acids Results in Propionyl-SCo. A
α-Oxidation of Branched Chain Fatty Acids Takes Place in Peroxisomes
Omega oxidation • Omega oxidation (ω-oxidation) is a process of fatty acid metabolism in some species of animals. • It is an alternative pathway to beta oxidation that, instead of involving the β carbon, involves the oxidation of the ω carbon (the carbon most distant from the carboxyl group of the fatty acid). • The process is normally a minor catabolic pathway for medium-chain fatty acids (10 -12 carbon atoms), but becomes more important when β oxidation is defective. • In vertebrates, the enzymes for ω oxidation are located in the smooth ER of liver and kidney cells, instead of in the mitochondria as with β oxidation.
ω-Oxidation in the ER of Liver Cells Minor pathway in mammals, more important in invertebrates
Oxidation of Unsaturated Fatty Acids (Remember they are cis!) After three round of βoxidation, the ene is in the wrong place. Easy, use an isomerase to get it between the alpha and beta carbons. But, this bypasses the first enzyme of β-oxidation making this round produce only 1 NADH (and no FADH 2).
Unsaturated Fatty Acids • • • Consider monounsaturated fatty acids: Oleic acid, palmitoleic acid Normal -oxidation for three cycles cis- 3 acyl-Co. A cannot be utilized by acyl. Co. A dehydrogenase Enoyl-Co. A isomerase converts this to trans 2 acyl Co. A -oxidation continues from this point
Multiple points of unsaturation can require energy to get them through βOxidation You don’t need to memorize these pathways, but you have to know this takes energy and NADPH to get the molecules into β-oxidation. The general lesson here is that each point of unsaturation reduces the amount of energy harvested by β -oxidation.
Polyunsaturated Fatty Acids Slightly more complicated • Same as for oleic acid, but only up to a point: – 3 cycles of -oxidation – enoyl-Co. A isomerase – 1 more round of -oxidation – trans- 2, cis- 4 structure is a problem! • 2, 4 -Dienoyl-Co. A reductase to the rescue!
Plant vs Animal β Oxidation Peroxisomes in Animals – mainly different in First Step and Usually use >20 C and branched chain fatty acids. Peroxisomes in Plants are main fatty acid oxidation (not in mitochondria)
- Slides: 60