30 Metabolic Processes of the Liver Flashcards
what GLUT transporter transports carbohydrates into the liver?
GLUT2
what is the effect on insulin and glucagon after a meal?
Insulin increases and glucagon decreases
what are the fates of glucose?
Can be broken down for energy (glycolysis)
can be stored as glycogen
galactose and fructose can be converted to glucose
excess carbs are converted to fat
what are the key enzymes in glycolysis?
glucokinase, phosphofructokinase, pyruvate kinase
what is the effect on insulin and glucagon?
Insulin decreases and glucagon increases
so in between meals, what is glycogen broken down into?
glucose for energy
what is the key enzyme that allows glycogen to be broken down into glucose for energy?
Glucose 6-Phosphatase (only in liver) allows glucose to exit the hepatocyte via GLUT2
what does gluconeogensis allow for?
alternate sources of glucose (amino acids, glycerol, lactate)
how are amino acids transported into the liver?
via Na-dependent and Na-independent transport
what are the fates of amino acids?
o Amino acids need to be utilized or broken down immediately
Synthesis of non-essential amino acids (transamination)
Deamination of amino acids yields a-keto acids and ammonia
Synthesis of plasma proteins
why is it that Amino acids need to be utilized or broken down immediately?
No storage form for amino acids
how is the amino acid fate through the synthesis of non essential amino acid?
transaminase
why is the fate of an amino acid the deamination of amino acids yields a-keto acids and ammonia?
a-keto acids can be used for the Krebs cycle, gluconeogenesis and ketogenesis
keep in mind that ammonia is converted to urea and so that Urea leaves the cell at the basolateral membrane
and is Excreted in urine
why does the amino acid fate lead to the synthesis of these plasma proteins?
albumin
blood clotting factors
apolipoproteins
glutathione
what is albumin?
it affects oncotic pressure and carrier proteins
what are apolipoproteins used for?
fat metabolism
what is glutathione used for?
drug metabolism and protection against oxidative stress
what vitamin is involved in blood clotting?
vitamin K
how does fatty acid transport in the lymph and blood work in the form of chylomicrons?
Chylomicrons enter lymphatics in the intestines and then enter the venous system at the root of the neck, thus ending up in the systemic circulation before reaching the liver
in the systemic system, how are the triglycerides broken up?
From the systemic circulation, fat and muscle endothelium lipoprotein lipases partially digest the triglycerides to fatty acids and glycerol for use in the cell
How does FA transport into the liver work?
Chylomicrons reach the liver as chylomicron remnants and so they are taken up by the liver using LDL related receptors
what is contained in the chylomicron?
▪ Chylomicron remnants contain less triglycerides and higher ratio of fatty acids and cholesterol
what is the fate of the FA?
acetyl CoA can be produced
fatty acids can be re-esterified to form triglycerides which are stored or exported as very-low-density lipoprotein (VLDLs)
Liver uses lipids in the synthesis of phospholipids, lipoproteins
What are the three zones of the liver?
zone 1-3
what is zone 1?
is closest to the portal tract and richest in O2
what is zone 2?
intermediate
what is zone 3?
closest to the central vein (hepatic venule) and lowest in O2 and exposed to modifications made by hepatocytes in earlier zones
what are examples of reactions that occur in zone 1?
Amino acid catabolism, gluconeogenesis, glycogenolysis, ureagenesis, oxidative energy metabolism
what are examples of reactions that occur in zone 3?
Glycolysis, glycogen synthesis, liponeogenesis, bile acid synthesis, biotransformation of drugs
What is the key for being able to use absorbed nutrients?
Portal system
What are Kupffer cells?
Macrophages in the liver that destroy ~99% of pathogens in the portal blood
How much storage of Vitamin A, D, and B12 is stored in the liver?
Vitamin A – 10 months
Vitamin D – 3-4 months
Vitamin B12 – Over 1 year
What do statin drugs block to help with cholesterol?
HMG-CoA reductase
This is the key enzyme (rate-limiting step) in cholesterol synthesis
What makes conjugated bilirubin from bilirubin?
UDP glucuronyl transferase
After conjugated, the bilirubin is actively excreted into bile via MRP2 transporter
What are the two hereditary hepatic disorders discussed that lead to jaundice?
Crigler-Najjar syndrome
Dubin-Johnson syndrome
what is Crigler-Najjar syndrome?
a UDP-glucuronyl transferase deficiency
Leads to unconjugated “indirect” bilirubin
what is Dubin-Johnson syndrome?
causes an MRP2 transporter defect and leads to conjugated “direct” bilirubin
What makes primary and secondary bile acids from cholesterol?
7α-hydroxylase
What are the three enzymes she wanted us to remember for testing liver function?
Alkaline phosphatase
Aspartate aminotransferase (AST)
Alanine aminostransferase (ALT)
what is Alkaline phosphatase?
Enzyme found in bone and the biliary system. Elevation could mean problem in the biliary system (intrahepatic or extrahepatic)
what is Aspartate aminotransferase (AST)?
Enzyme found in hepatocytes (and other cells). Elevation could mean active hepatocyte injury.
what is Alanine aminostransferase (ALT)?
Enzyme found in hepatocytes (and other cells). Elevation could mean active hepatocyte injury.
