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40 terms

NTD411 - Lipids (metabolism)

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lipoprotein lipase
an enzyme that hydrolyzes the ester linkage between a fatty acid and a glycerol in a triglyceride molecule as it circulates in the bloodstream
hormone sensitive lipase
an enzyme that catalyzes the hydrolysis of ester linkages that attach fatty acids to the glycerol molecule; mobilizes fatty acids from adipose tissue
lipogenesis
the cyclic metabolic process that results in fatty acid and, ultimately, triglyceride synthesis through the repeated process of adding 2 carbons onto the acetyl CoA starter; requires initial ATP & NADPH (as a hydrogen donor)
lipogenesis steps
acetyl coa condenses w/ malonyl coa (loses co2); malonyl coa is reduced (NADPH) and dehydrated, then further reduced (hydrogenation); repeat process until a 16c saturated fatty acid is produced
lipogenesis: location, enhancers, inhibitors
cytosol of liver (+ some adipose tissue); high simple sugar/low fat diet, insulin, inc acetyl coa carboxylase activity, ATP; glucagon, dietary fat, starvation
cholesterol synthesis has ___ basic stages:
3: formation of HMG-CoA from acetyl CoA, production of squalene from HMG-CoA (rate limiting step requiring HMG CoA reductase), eventual production of hcolesterol from cyclization of squalene
cholesterol synthesis: location
20% liver
digestion of triacylglycerols
1. Mouth: chewing breaks apart food, lingual lipase starts hydrolyzing fatty aicds from glycerol molecules 2. Stomach: lingual lipase continues; stomach releases gastric lipase from gastrin (secreted w/ presence of fat in stomach) but most action occurs via emulsification via contractions 3. small intestine: more conducive pH environment; a) partially hydrolyzed lipids enter as lipid droplets and become further emulsified via mechanical means & bile release from the gallbladder as a result of cck; micelles form w/ phospholipids & cholesteryl esters b) in the duodenum, secretin (SI) stimulates the pancreas to release pancreatic lipase to complete triglyceride digestion into fatty acids and monoacylglycerol from wtihin the micelles
digestion of phospholipids, cholesterol & cholesteryl esters
phospholipids are digested by phospholipase A from pancreas in response to secretin resulting in 1 fatty acid and 1 molecule of lysophospholipid; cholesteryl esters must be broken down into their cholesterol and fatty acid constituents via vile salt dependent cholesteryl ester hydrolase in response to secretin
absorption
occurs in the distal duodenum and jejunum; micelles are water soluble enough to get through the layers lining the enterocyte and allow their contents (FFA, 2-monoacylglycerols, cholesterol/esters, lysolecithin) to diffuse out into the enterocytes down a concentration gradient; short & medium FA pass directly into the portal blood to liver bound to albumin; other components reform triacylglycerols, phosphatidylcholine, and cholesteryl esters
transport & storage
lipids are surrounded by lipoproteins and fuse with golgi apparatus to form chylomicrons, leaving the cell membrane and entering lymphatic circulation
apolipoproteins
the protein portion of any lipoprotein; play an important role in structural and functional relationship among lipoproteins (stabilize the lipoprotein as a whole, act as recognition sites for receptors, stimulate enzymatic reactions)
VLDL
made in the liver from endogenous triacylglycerol; function in the transport of triacylglycerol from liver to other, non-hepatic tissues; also contain cholesterol & cholesteryl esters; deliver fatty acids to cells via lipoprotein lipase
IDL
brief intermediary stage that occurs as triacylglycerol molecules are removed from VLDL; taken up by the liver or remain in circulation; eventually converted to LDLs
LDL
type of lipoprotein that IDL's become when enough TAG's are removed; major cholesterol carrier to tissues for membrane construction or conversion into other metabolites; receptors needed to get TAG's into cells and remove LDL from circulation
classes of inadequate LDL functioning
1: no receptors synthesized 2: precursor synthesized but not properly processed 3: synthesized & processed but in a faulty way 4: receptors bind w/ LDL but can't cluster in the coated pits; inadequate # receptors caused by high saturated fat & cholesterol in diets
HDL
lipoprotein made in the liver that circulates in the blood to collect excess cholesterol from the cells; reverse cholesterol transport back to liver
storage
adipocytes are major site; constant TAG turnover here
if glucose exceeds glycogen stores, excess is turned into ____ leading to ____
fatty aicds, overproduction of vLDL
chylomicron remnants
the lipoprotein particle that remains after a chylomicron has lost most of its fatty acids; taken up by the liver for reuse or recycling.
uses for glycerol vs. fatty acids
used for energy by the liver through glycolytic pathways; oxidative potential in the krebs cycle
beta-oxidation of fatty acids
a cyclic degradative pathway in the mitochondria of all cells but brain & RBC by which 2-carbon units in the form of acetyl CoA are cleaved one by one from the carboxyl end
beta oxidation: short vs. long chain FA
short pass directly into matrix; long use carnitine as a transport system
beta-oxidation requires ___, but each C-C saturated bond cleavage yields ____
2ATP, 5ATP
there are ___ ketone bodies:
3: beta-hydroxybutyrate, acetone, acetoacetate
why would ketone formation occur?
accumulation of acetyl coa due to insufficient quantities of oxaloacetate from glucose breakdown to combine with it in krebs
ketone formation process
2 molecules acetyl coa condense to form acetoacetate, which can decarboxylate spontaneously to form acetone (end of the road) or converted to beta-hydroxybutyrate
ketosis
results from an overproduction of ketone bodies and can disturb acid-base balance and lead to ketoacidosis
ketoacidosis
severe ketosis leading to lowered blood pH, nausea, coma, death
regulation of fatty acid metabolic processes
linked to carb status: hyperglycemia + insulin promotes glucose transport into adipose cells (lipogenesis); hypoglycemia + low levels of insulin favor lipolysis; hormone sensitive lipase is stimulated by epinephrine, norepinephrine, glucagon, etc. to mobilize fat
ethyl alcohol
neither a carb nor a lipid, but with a structure that resembles a carbohytes and a metabolism that resembles a fatty acid catabolic process; preferentially treated by liver (will break down and ignore sugar, fat, etc.)
ethyl alcohol: source, calorie content
alcoholic beverages, 7kcal/gram
ethyl alcohol: absorption & transport
throughout entire GI tract, transported unaltered in bloodstream
ethyl alcohol: metabolism
oxidatively degraded in tissues (especially liver) via alcohol dehydrogenase (ADH), forming NADH & acetyl CoA, which works until NAD+ is depleted or concentration rises too high
why is ethyl alcohol metabolism lipogenic?
depletion of NAD+ means that the krebs cycle can't run to burn fats for energy
complicationsof alcoholism
acetyaldehyde toxicity, high NADH:NAD+ ratio, substrate competition
acetaldehyde toxicity
Both ADH + MEOS routes produce acetaldehyde, which can attach covalently to proteins to form protein adducts; could impair enzyme activity, impede the formation of microtubules in liver, leads to cirrhosis
high NADH:NAD+ ratio
leads to fatty liver due to upregulation of acetyl coa carboxylase
acetyl coa carboxylase
the enzyme responsible for converting acetyl coa into malonyl coa; key regulatory enzyme for fatty acid synthesis
substrate competition of ethyl alcohol
especially with retinol