Lipid Metabolism Overview and Diseases of Lipid Metabolism
Overview of lipid metabolism Most important form of energy storage You’d have to store 67.5 lbs of hydrated glycogen to equal the energy contained in 10 lb of stored fat Relative proportion of stored energy • Carbohydrates: 650 kcal [1 kcal = 1 cal (dietary)] • Protein: 25,000 kcal • Fat: 100,000 kcal
Three sources Dietary triacylglycerols (TAGs) TAGs synthesized in liver TAGs stored in adipocytes Many diseases associated with disruptions in lipid metabolism
Why Fatty Acids for energy storage? Two reasons: • The carbon in fatty acids (mostly CH2) is almost completely reduced (so its oxidation yields the most energy possible). • Fatty acids are not hydrated（水化） (as mono- and polysaccharides are), so they can pack more closely in storage tissues
Fat from Diet & Adipose Cells Triacylglycerols either way • Triglycerides represent the major energy input in the modern diet (but it wasn‘t always this way). • Triglycerides are also the major form of stored energy in the body. • Hormones (glucagon, epinephrine, ACTH) trigger the release of fatty acids from adipose tissue
Hormones Signal from Adipose Tissue The hormone molecules bind to receptors on the plasma membrane of adipose cells and lead to the activation of adenylyl cyclase to cAMP
Hormones Signal from Adipose Tissue cAMP activates protein kinase A, which phosphorylates and activates a triacylglycerol lipase (TAG lipase). The TAG lipase hydrolyzes a fatty acid from C-1 or C-3 of triacylglycerols. Subsequent actions of diacylglycerol lipase and monoacylglycerol lipase yield fatty acids and glycerol. The cell then releases the fatty acids into the blood, where they are bound to serum albumin. Serum albumin transports free fatty acids to sites of utilization
Degradation of Dietary Fatty Acids Dietary TAGs are degraded by stomach lipases, pancreatic lipase and nonspecific esterases in stomach and duodenum respectively. The FAs pass into the epithelial cells, where they are condensed with glycerol to form new TAGs. These TAGs aggregate with lipoproteins to form particles and are then transported to the other organs. At these sites, the TAGs are hydrolyzed to release FAs, which can be oxidized in a highly exergonic metabolic pathway. /ˌeksəˈgɒnɪk/放能的
Disease of Lipid metabolism Atherosclertosis Athero = paste Sclerosis = hardness A slow progressive disease Characterized by hardening of the arteries due to lipid accumulation in blood vessel walls
Atherosclertosis 50% of all deaths in U.S. linked to this vascular disease Inflammation initiated and perpetuated by leukocytes (white blood cells) Plaque forms, containing cholesterol, dead macrophages, and calcified muscle. Rupture of plaque releases blood clot Heart attack – disruption of circulation to heart Stroke – disruption of circulation to brain Lipids deposited by lipoproteins