Liver Biochemistry Flashcards
structure of the liver
largest solid organ
weights 1500 g
2 lobes subdivided into multiple lobes and sinusoids
75% supplied by portal vein
25% by hepatic artery
biliary component made of bile ducts and gallbladder
liver cell types
hepatocytes endothelial cells kupffer cells hepatic stellate cells pit cells (lymphocytes)
functions of the liver
primary receiving, distribution and recycling center lipid biosynthesis and management protein biosynthesis - albumin and IgG nitrogen metabolism - urea cycle waste management - xenobiotic reactions bilirubin metabolism fuel management
central receiving, distribution, and recycling center
major role: monitoring, synthesizing, recycling, distributing, and modifying metabolites
ingested material is retrieved by the liver and converted into a useful form
harmful products are converted into a safe product
structural adaptations
enteric circulation - portal vein
periphery - hepatic a
lack basement membrane, has gap junctions and fenestrations and low portal blood pressure which allow greater access and increased contact b/w liver and blood
hepatocytes
well developed, plasma membrane w/ endocytic and exocytic system, well developed ER, metabolically active cells, lots of mitochondria, lots of lysosomes
features of isoprenoids
3 acetyl CoA used to generate IPP which serves as a building block for the synthesis of all isoprenoids including steroids and lipid soluble vitamins
sources of acetyl CoA
oxidative decarboxylation of pyruvate
beta oxidation of FA
breakdown of AA
transported into cytoplasm via citrate shuttle
cholesterol
precursors of: bile acids and salts, vit D, and steroid hormones
fate of cholesterol - all tissues
incorporated into cellular membranes
fate of cholesterol - liver
synth bile acids
fate of cholesterol - adrenal glands, ovaries, testes
synth steroid hormones
fate of cholesterol - skin
synth vit. D
lipid rafts
microdomains enriched in cholesterol
detergent insoluble low buoyant density
local centers for signal transduction processes
sites for abnormal processing of proteins in neurodegenerative disorders
direct inhibition
inhibited by FFA, bile acids, oxysterols
inhibited by statins (competitive inhibitors)
covalent modification
active - de pi inactive - pi low energy leads to pi and inactivation glucagon inhibits by preventing de pi insulin activates by promoting de pi
transcriptional control
SREBP-SCAP complex is retained in ER in the presence of cholesterol which leads to low transcription rate
low sterol promotes release
translational and post-translational control
translation is reduced by vitamin E
cholesterol leads to interaction of INSIG which will release from ER
role of liver in cholesterol homeostasis
cholesterol biosynthesis happens in liver
VLDL to LDL
cholesterol delivered to liver via chylomicron
major source of nascent HDL
helps clear bulk of lipoproteins
synthesizes bile acids and eliminates cholesterol into bile
statins
lower cholesterol
strong competitive inhibitors of HMG CoA reductase
increase in SREBP maturation which leads to transcription of LDL R and increased clearance of cholesterol
cytochrome P450 and drug interactions
converts linear isoprenoid squalene into cholesterol
detoxify stains
inhibition leads to toxic side effects of statins
hepatic cholesterol
a precursor of bile acids and bile salts
strong detergents
amphipathic with polar and non polar regions
bile
made in hepatocytes
stored and concentrated in gallbladder
lipid emulsifying mixture
acids in lipid digestion by forming micelles which increase surface area of lipids exposed to lipases
gallstones
crystals made of bile supersaturated with cholesterol
treated with ursodeoxycholic acid
cholelithiasis
insufficient secretion of bile salts or phospholipids or excess cholesterol secretion
