Stiner - The Role of the Liver in Metabolism Flashcards
This organ is where all ingested materials are filtered through, the cells have a broad range of synthetic, catabolic, and excretory function; where most drug metabolism takes place
the liver
With ______ liver disease there are typically ___ outward symptoms, but with ______ liver disease, ______ symptoms are present
mild
no
severe
many
The ______ of the liver facilitates the exchange of metabolites between _______ and _______
structure
hepatocytes and plasma
The liver plays a central role in _______ metabolism by maintain the circulating concentration of it
glucose
This enzyme permits the release of ___ _____ to the blood by hydrolysis of itself resulting in the creation of a ____ ____ and ____ _____
glucose-6-phosphate
free glucose
phosphate group
free glucose
_____ store more glycogen than the liver
muscles
The majority of plasma proteins (albumin, coagulation factors, α/β globins, acute phase proteins) are synthesized in the _______
liver
Genetic deficiency of _________ presents in infancy as liver disease or in adulthood as lung disease
α1-antitrypsin
Genetic deficiency of ______ leads to Wilson’s disease, a condition associated with liver and CNS damage
ceruloplasmin
Liver cancer is associated with particularly high plasma concentrations of __________
α-fetoprotein
Plasma proteins and membrane receptors are ________ and then ______ by acid proteases within intracellular organelles known as _________
endocytosed
hydrolyzed
lysosomes
Intracellular proteins are degraded within structures known as _______, by the ______-_______ system
proteasomes
ubiquitin-proteasome (UPS)
________ marks intracellular proteins for degradation
ubiquitin
UPS involves three enzymes, what are they?
an ATP-dependent ubiquitin-activating enzyme (E1)
ubiquitin-conjugating enzyme (E2)
ubiquitin-protein ligase (E3)
The UPS is important in the activation of the ______ ______ pathway and the function of UPS is _______ by ROS
NFκB proinflammatory
modified
The ____ ____ is essential for the removal of nitrogen generated via amino acid metabolism; detoxification of ammonia/alanine to _____ in the liver
urea cycle
urea
Ammonia is toxic, particularly to the _______; impaired clearance of ammonia can cause ______ ______
CNS
brain damage
_______, a constituent of hemoglobin, myoglobin, and cytochromes, is synthesized in most cells of the body (the liver is the main non erythrocyte source of its synthesis)
heme
Heme synthesis-1: glycine and succinyl-coenzyme A condense to form _____________ and this reaction is catalyzed by _______; located in the __________
5-aminolevulinate (5-ALA)
5-ALA synthase
mitochondria
The rate limiting step of heme synthesis is the inhibition of _________
5-ALA synthase
Heme synthesis-2: In the ________, two molecules of 5-ALA condense to form a molecule containing a pyrrole ring, ______________
cytosol
porphobilinogen (PBG)
Heme synthesis-3: Four molecules of PBG combine to form a _______ ______ compound which cyclize to yield ____________ and then __________
linear tetrapyrrole
uroporphyrinogen III
coporphyrinogen III
Heme synthesis: Final stages (1 of 2) occur in the _______ where a series of carboxylation/decarboxylation of side chains in uroporphyrinogen III yield _________
mitochondria
protoporphyrin IX
Heme synthesis: The last stage is where iron (Fe2+) is added by _________ to _________ to form heme
ferrocheltase
protoporphyrin IX
________ is the catabolic product of heme; it is excreted into bile and urine and responsible for the yellow color of bruises, jaundice, etc; coagulation of it in the gut is catabolized by bacteria
bilirubin
Bilirubin, when oxidized, reverts to become _______; and this cycle has led to the theory of bilirubin as a cellular ________
biliverdin
antioxidant
True or False
Bilirubin is soluble and biliverdin is not
False; biliRUBIN is NOT soluble and biliVERDIN is soluble; bilirubin must be transported by a carrier protein
_______ is clinically obvious when plasma bilirubin concentration exceed 50μmol/L; result of an imbalance between production and secretion; there are 3 main causes
jaundice
Three main causes of jaundice;
________ is the increased production of bilirubin
________ is impaired hepatic uptake, conjugation, or secretion of bilirubin
______ is the obstruction of biliary drainage
prehepatic
intrahepatic
posthepatic
_______ _______ results from excess production of bilirubin as a result of hemolysis, or a genetic abnormality
prehepatic jaundice
_______ ______ reflects a generalized hepatocyte disfunction; lack of bilirubin processing; common in newborns
intrahepatic jaundice
______ _______ is caused by an obstruction of bilirubin “tree,” the plasma bilirubin is conjugated and other biliary metabolites, such as bile acids, accumulate
posthepatic jaundice
Metabolism of drugs proceeds in 2 phases:
phase 1 –> the addition of a _____ group mediated by _______
phase 2 –> _______ mediated by cytoplasmic enzymes, ______, ______, _____
polar
cytochrome C P-450 (CYP)
conjugation
sulfination, acetylation, methylation
Active site of CYP contains a ____ ____ center; important for the ________ of organic substances; accounts for ~75% of total ____ _____
heme iron
oxidation
drug metabolism
The __________ enzyme family is responsible for drug breakdown; present in the ______ _____ mainly in the liver; can be inhibited by agents such as grapefruit juice; these enzymes can also exhibit _____ _____ that can alter catalytic activity
cytochrome P-450
endoplasmic reticulum
allelic variance
The commonly prescribed drug _______ can be hepatotoxic in excess; an overdose can cause free radical mediated peroxidation of membrane lipids
acetaminophen
Excess intake of ____ ____ remains the most common cause of liver disease in the western world; it can also affect the ubiquitin system
ethyl alcohol
________ deaths associated with liver disease in the US annually and _____% of these are linked to alcoholic cirrhosis
25,000
40%
Ethanol is oxidized in the liver by _____ ________ to form ________
alcohol dehydrogenase
acetaldehyde
Acetaldehyde is oxidized by ________ to form ______
acetaldehyde dehydrogenase (ALDH) acetate
______ ______ _____ is the cofactor for the ethanol –> acetaldehyde –> acetate reaction
nicotinamide adenine dinucleotide (NAD+); is reduced to NADH
Liver damage in patients who abuse alcohol may arise from the toxicity of _________
acetaldehyde
Both alcohol dehydrogenase and acetaldehyde dehydrogenase are susceptible to _____ _____; which can increase/decrease rise of liver disease/alcoholism
genetic polymorphisms
Increase
Biochemical tests to measure “liver function” work by testing levels of ______ ______; fluctuations in these can be an indicator of disease
liver enzymes (bilirubin, albumin, etc)
____ _____ is a good indicator of liver synthetic function
prothrombin synthesis
_______ ______ and ______ ___-_____ are involved in the interconversion of amino and ketoacids, and are required for metabolism of nitrogen and carbohydrates; both are in the mitochondria and serum activity increases in liver disease
aspartate aminotransferase (AST) alanine amino-transaminase (ALT)
In liver disease, the synthetic functions of ________ are likely affected, and so the patient would be expected to have a ______ prothrombin time (clotting) and a ______ serum albumin concentration
hepatocytes
prolonged
low
An increased level of ________ is indicative of impairment of heme catabolism
Bilirubin
A decreased level of _________ is indicative of impaired Carbohydrate metabolism
Glucose
An increased level of ______ and a decreases level of ________ is indicative of impairment of Protein synthesis
Prothrombin time
Albumin
An increased level of ___________ and a decreased level of __________ is indicative of impairment of protein catabolism
Ammonia
Urea
An increase of _______ and ______ is indicative of an impairment of lipid metabolism
Cholesterol
Triglycerides
An increase of _________ is indicative of an impairment with drug metabolism
Drug half time
An increase in ____ _____ is indicative of an impairment of bile acid metabolism
Bile acids
