Liver Metabolism BCH & LFTs Flashcards
__________ is the major source of energy for the liver during the Fed state
Glucose (Glycolysis and PPP)
Glucose-6-Phosphate are diverted through the _________ to generate ATP and produce NADPH
PPP (Pentose Phosphate Pathway)
______________ is the end-product of glycolysis and is converted to ________ _____ which can enter the TCA cycle to ultimately generate ATP
Pyruvate; Acetyl CoA
Excess Acetyl CoA and NADPH in the liver is used to synthesis…
fatty acids
Amino acids are used as a major energy source for the liver (True or False)
False: used to make liver proteins and other nitrogen compounds
In the early Fasting State, the liver’s main function is to….
mobilize glycogen stores to maintain blood glucose
What does the liver use for energy during the Fasting State
B-oxidation of fatty acids for Acetyl-CoA
The liver synthesizes __________ __________ from __________ for export to muscles and the brain during the Fasting State
Ketone bodies; Acetyl-CoA
The high level of protein catabolism in the liver during the Fasting State generates a large amount of _________, making the Urea Cycle CRITICAL for clearance
urea
chemical substances that are NOT normally produced by an organism; pharmaceuticals, antibiotics and pollutants are examples
xenobiotics
Xenobiotics are (poorly/very) soluble in plasma
Poorly (making them difficult to excrete)
Process by which the liver alters the chemical properties of xenobiotics (unnatural compounds) to change the activity and increase solubility to allow excretion in the urine; involves Phase 1 and 2 reactions
Biotransformation
(Phase 1 or Phase 2)
Biotransformation of xenobiotics; carried out by CYP450 enzymes; usually hydroxylation; ROS are an intermediate, which is why massive overdoses can harm hepatocytes
Phase 1
(Phase 1 or Phase 2)
Biotransformation of xenobiotics; conjugation reactions to make a xenobiotic more easily excreted (via glucuronidation or sulfate addition)
Phase 2
Two primary pathways for the liver metabolism of ethanol
1st: Alcohol Dehydrogenases
Back-up: MEOS (CYP2E1 enzymes)
Describe the metabolism of ethanol
Ethanol–> Acetaldehyde–> Acetate–> Acetyl-CoA–> Ketone Bodies
(ADH vs. CYP2E1) are the main metabolizers of alcohol at mild-moderate levels; have a low Km for ethanol
ADH (Alcohol Dehydrogenase)
(ADH vs. CYP2E1) are the backup metabolizers of alcohol; activated at high ethanol concentrations and produce ROS in the process
CYP2E1
Within macrophages, heme oxygenase catalyzes heme into a green pigment known as _____________
biliverdin
Biliverdin is a byproduct of heme oxidation, and is subsequently reduced to a red-orange pigment called _____________
bilirubin (also called unconjugated bilirubin)
byproduct of heme; red-orange pigment; poorly soluble in the plasma and can cross the blood-brain barrier; bound to plasma albumin the transport from macrophages to hepatocytes
Bilirubin
How is unconjugated bilirubin safely transported through the blood to hepatocytes?
Immediately bound to plasma albumin, and allowed into hepatocytes by Organic Anion Transporting Polypeptides (OATP)
What membrane protein allows unconjugated bilirubin into the hepatocytes
Organic Anion Transporting Polypeptides (OATP)
Enzyme in hepatocytes ER that catalyzes the glucuronization of bilirubin to conjugated bilirubin
Uridine Diphosphate Glucuronosyl Transferase (UGT)
Conjugated bilirubin is transported into the bile canaliculi via what transporter; RATE LIMITING step of secretion
cMOAT (Canalicular Multispecific Organic Anion Transporter) (also known as MRP-2: Multidrug Resistance Protein 2)
colon enzyme that removes the glucuronic acid molecules from bilirubin to a colorless compound called urobilinogen
beta-glucuronidase
Most urobilinogen in colon is converted by bacterial enzymes by…
stercobilinogen
what gives feces its characteristic dark brown color
stercobilinogen (conversion of urobilinogen)
Normal concentration of bilirubin in the blood
< ~ 1 mg/ml
physical characteristic that is due to hyperbilirubinemia; yellow pigmentation of the skin, conjunctival membranes and other mucous membranes
Jaundice
How does liver get rid of excess cholesterol
synthesis of bile acids
laboratory tests used to help identify the presence of liver disease; the pattern and degree of elevation can provide information about the underlying etiology, severity, and prognosis of the liver disease; can also be used to monitor response to medical therapy
Liver Functions Tests (LFTs)
Examples of Liver Function Tests
AST (aspartate)* ALT (alanine)* Alkaline phosphatase* GGT* Bilirubin Albumin PT/INR
*represent liver injury (others represent liver function)
Which Liver Function Tests indicate hepatocellular injury
AST and ALT (elevations are indicative of injury)
Which Liver Function Tests indicate cholestatic injury (bile duct obstruction)
Alkaline phosphatase, GGT and Bilirubin
markers of hepatocellular injury; “aminotransferases”; they are enzymes that play a role in gluconeogenesis under periods of stress (such as injury)
AST and ALT
Which is more specific for hepatocyte injury: AST or ALT
ALT (AST is present in many tissues besides liver, such as heart, skeletal muscle and brain)
LFT that indicates cholestatic injury; is a hydrolase enzyme that is most prominent in the bile canaliculi; an impairment of biliary flow (cholestasis) will result in elevated levels due to back-up
Alkaline Phosphatase
LFT that indicates cholestatic injury; transfers y-Glutamyl groups between amino acids; concentrated in epithelial cells lining fine ductules; MORE sensitive than Alkaline phosphatase
y-Glutamyl Transferase (GGT)
In cases of liver injury, levels of ___________ and ___________ will decrease
Albumin and clotting factors
Pre-hepatic causes of jaundice lead to an elevation of (conjugated/unconjugated) bilirubin
unconjugated (or indirect) bilirubin (occurs PRIOR to uptake and conjugation in liver)
Post-hepatic causes of jaundice lead to an elevation of (conjugated/unconjugated) bilirubin
conjugated (or direct) bilirubin (occurs AFTER the uptake and conjugation in liver)
Examples of causes of prehepatic jaundice (unconjugated bilirubin)
Hemolysis
Sickle cell crisis
Blood transfusion
(events that occur PRIOR to the uptake of bilirubin and conjugation in the liver)
Examples of intrahepatic jaundice (both conjugated and unconjugated bilirubin)
Hepatitis
Cirrhosis
Hepatocellular Carcinoma
Primary Sclerosing Cholangitis
Examples of post-hepatic jaundince (conjugated bilirubin)
Choledocholithiasis
Primary Sclerosing Cholangitis
Pancreatitis
Pancreatic carcinoma (at the head)
AR disorder of bilirubin conjugation; caused by alteration of UGT1A1 gene; most common hereditary hyperbilirubinemia syndrome
Gilbert Syndrome
AR disorder of bilirubin conjugation; caused by alteration of UGT1A1 gene; either absent activity (Type 1) or reduced activity (Type II)
Crigler-Najjar
AR disorder of bilirubin reuptake and storage
Rotor Syndrome
In the setting of liver disease, the most important aspect of liver imaging is to evaluate for…
biliary duct obstruction
If liver imaging does not provide a clear etiology for disease, what else can be done for diagnosis…
Biopsy (percutaneous or transjugular)
