Lipid and AA Metabolism Flashcards
lipid digestion begins…
minimally in mouth
once lipids make it to the duodenum…
bile aids lipids in emulsification to inc lipid SA
role of pancreas in lipid digestion
release lipase, colipase, and cholesterol esterase to hydrolyzes lipid on 2-monoacylglycerol, free FA, and cholesterol
at the end of the ileum
micelles experience reabsorbtion as the ileum reabsorbs bile salts and any remaining fat is passed onto the colon
micelles are absorbed by…
- brush border of intestinal mucosal cells
- made into triacylglycerols and cholesteryl esters in mucosa to form chylomicrons
how do chylomicrons leave the intestines?
lacteals, re enter bloodstream via the thoracic duct, and empty into subclavian vein
A fall in insulin levels can activate which lipid management enzymes?
HSL, hydrolyzes triacylglycerols to form FA and glycerol
which hormones activate HSL?
epi, and cortisol
HSL role
released glycerol transported to liver
triacylglycerol hydrolization
LPL role
- necessary for the metabolism of chylomicrons and very low density lipoproteins
- releases free fatty acids from triacylglycerols
VLDL role
transporta triacylglycerols and FA from liver to tissues
IDL role
picks up cholesteryl esters from HDL to become LDL
picked up by liver
LDL
deliver cholesterol to cells
HDL
helps in lipoprotein formation
picks up cholesterol in blood vessels
and delivers it to liver and steroidogenic tissue
cholesterol derivation
LDL
HDL
de novo synthesis
describe de novo synthesis of cholesterol
- occurs in liver
- driven by acety CoA and ATP
- citrate shuttle carries acetyl CoA from mitochondria to cytoplasm
- NADPH (pentose phosphate pathway) helps in reduction
- mevalonic acid synthesis by HMG CoA reductase in SER
cholesterol synthesis regulation
- insulin promotes
- cholesterol net feedback
- HMG-CoA reductase gene expression regulation
LCAT
- cholesterol transport
- bloodstream
- activated by HDL
- adds a FA to cholesterol
- CETP facilitates transfer of cholesteryl esters to other lipoproteins like IDL to form IDL
where does FA synthesis occur
- liver
- adipose
how does acetyl CoA make it to the cytosol? first step of FA synthesis
- produced by PDH and couples with OAA to form citrate TCA
- citrate can then diffuse across mitochondrial membrane and in cytosol lyase splits them
- OAA returns to mitochondria to continue shuttling
rate limiting step of FA synthesis
- acetyl-CoA carboxylase using biotin and ATP to add CO2 to acetyl coa to form malonyl CoA
- activated by insulin and citrate
fatty acid synthase
- B5 and NADPH required
- malonyl CoA + acyl carrier protein ~> malonyl-ACP
- palmitate formed
where does triacylglycerol formation occur
liver, sent to adipose as VLDL
describe the steps of FA catabolism
1) activation: FA attached to CoA by FA-CoA synthase
2) entry into mitochondria: large FA chains cannot diffuse and require carnitine shuttle via carnitine acyltransferase I to enter mitochondria
3) β-oxidation
describe β-ox
- releases one acetyl CoA (fasting state in liver and ketone synthesis), reduced NAD+ and FAD to NADH and FADH2
1) ox of FA to form double bond
2) hydration of double bond to form a hydroxyl group
3) oxidation of hydroxyl group to form carbonyl
4) splitting of B-ketoacid into shorter acyl or acetyl-CoA
5) even numbered FA forms 2 acetyl CoA, odd forms 1 acetyl Coa and 1 propionyl CoA, and by propionyl-CoA carboxylase makes methylmalonyl-CoA using B7 which then turns into succinyl CoA USING MUTASE AND B12 for TCA
6) in unsat additional isomerase and reductase required
in a fasting state, liver converts acetyl coa from B-ox into…
ketone bodies
acetoacetate or B-hydroxybutyrate
ketogenesis
- mitochondria of liver cells
- HMG CoA synthase, and then lyase follows and the acetoacetate formed can be reduced to 3-hydroxybutyrate
- acetone product
ketolysis generally
transferase activates acetoacetate from blood
oxidized to acetoacetyl-CoA (cannot occur in liver)
ketolysis in brain
indirectly metabolize FA as ketone bodies after a long time of fasting
ketones metabolized to acetyl CoA and PDH inhibited
glycolysis and glucose uptake inhibited
protein catabolism
- proteins digested in small intestine down into aa, peptides
- passive transport of aa into bloodstream
- catabolized primarily in muscle and liver
- transamination
- glucogenic aa converted to glucose
- ketogenic form ketones and acetyl coa
- amino groups feed into urea cycle
