Cholestwerol Flashcards
NADPH in biosynthesis of cholesterol
NADPH helps catalyse the final reaction of several
the C=C bond is reduced by transfer of a hydride ion
synthesis of cholesterol from acetyl CoA
Acetyl CoA + Acetyl CoA CONDENSATION
Acetoacetyl CoA + acetyl CoA CONDENSATION [HMG-CoA synthase]
HMG-CoA + 2NADP+ + CoA [HMG-CoA reductase under -ve feedback from cholesterol, mevalonate and bile salts]
mevalonate phosphorylated 3 times [melavonate kinase, phopho mevalonate kinase, kinase] DECARBOXYLATION [phospho mevalonate decarboxylase]
3-isopentenyl pyrophosphate + dimethylallyl pyrophosphate [geranyl transferase]
geranyl pyrophosphate + 3-isopentenyl pyrophosphate [geranyl transferase]
farnesyl pyrophosphate
squalene 30C + oxygen + NADPH + H+ – squalene epoxide + water + NADP+ [squalene monooxygenase]
squalene epoxide + H+
protosterol cation - H+
lanosterol REDUCTION -3 methyl units
cholesterol
Cholesterol and steroid hormones
all main steroid hormones from cholesterol
Synthesis of vitamin D from cholesterol
7-dehydrocholesterol + UV
prvit D3
Vit D3
Calcitriol HYDROXYLATION
Bile salts
cholesterol unfold forming polar and non-polar face
generated in liver
stored in gall bladder
major product of break down of cholesterol
cholesterol converted to glycocholate and taurocholate
Describe lipoproteins
composed of phospholipid monolayer containing cholsesterol and apoproteins
in core of lipoprotein are cholesterol esters and triacylglycerols
Cholesterol esters
synthesised in plasma
from cholesterol and acyl chain of phosphatidylcholine (lecithin)
catalysed by lecithin cholesterol acyltransferase (LCAT)
make more hydrophobic
acyl CoA acyltransferase (ACAT) - generate esters from long chain fatty acyl CoA species - intracellular enz - cholesterol taken in by endocytosis
Categories of lipoproteins
chylomicrons (CM) - cholesterol from diet
Very low density lipoproteins VLDL
intermediate desity lipoproteins IDL
Low density lipoproteins LDL - bad cholesterol
High density lipoproteins HDL - good cholesterol
Fat digestion
lipid digestion by lingual, gastric and pancreatic lipases - monoacylglycerol (MAG) and diacylglycerol (DAG) and free fatty acids that are released by lipid hydrolysis - join with BS and CL and lysophosphatidic acid (LPA) and fat soluble vitamins to form mixed micelles
fat absorption
absorbed by enterocytes that line brush border of SI
TAGs resynthesized
absorbed into chylomicrons
transported via lymphatics and to blood stream
High levels of LDL
atherosclerosis - artery hardening
transported to peripheral tissues
LDL and familial hypercholesterolaemia
monogenic dominant
2-3x more cholesterol
homozygous 5x
deposition of LDL into macrophages of skin
LDL receptor - ligand binding domain, EGF precursor homology domain, o-linked carb domain, transmembrane domain, cytoplasmic domain
recall four examples of blood-borne hormones which act as metabolic regulators
Insulin, glucagon, adrenaline, glucocorticoids
insulin
increase glucose take up
formation of glycogen
formation of fatty acids in adipocytes
increase number of glucose transporters on surface of liver cells
islets of Langerhans
increased use of metabolic substrates - synthesis
Glucagon
triglyceride break down gluconeogenesis in liver glycogenolysis break down proteins use of fatty acids islets Langerhans
