Stiner - The Role of the Liver in Metabolism

Question 1

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

Answer 1

the liver

Question 2

With ______ liver disease there are typically ___ outward symptoms, but with ______ liver disease, ______ symptoms are present

Answer 2

mild
no
severe
many

Question 3

The ______ of the liver facilitates the exchange of metabolites between _______ and _______

Answer 3

structure

hepatocytes and plasma

Question 4

The liver plays a central role in _______ metabolism by maintain the circulating concentration of it

Answer 4

glucose

Question 5

This enzyme permits the release of ___ _____ to the blood by hydrolysis of itself resulting in the creation of a ____ ____ and ____ _____

Answer 5

glucose-6-phosphate

free glucose
phosphate group
free glucose

Question 6

_____ store more glycogen than the liver

Answer 6

muscles

Question 7

The majority of plasma proteins (albumin, coagulation factors, α/β globins, acute phase proteins) are synthesized in the _______

Answer 7

liver

Question 8

Genetic deficiency of _________ presents in infancy as liver disease or in adulthood as lung disease

Answer 8

α1-antitrypsin

Question 9

Genetic deficiency of ______ leads to Wilson’s disease, a condition associated with liver and CNS damage

Answer 9

ceruloplasmin

Question 10

Liver cancer is associated with particularly high plasma concentrations of __________

Answer 10

α-fetoprotein

Question 11

Plasma proteins and membrane receptors are ________ and then ______ by acid proteases within intracellular organelles known as _________

Answer 11

endocytosed
hydrolyzed
lysosomes

Question 12

Intracellular proteins are degraded within structures known as _______, by the ______-_______ system

Answer 12

proteasomes

ubiquitin-proteasome (UPS)

Question 13

________ marks intracellular proteins for degradation

Answer 13

ubiquitin

Question 14

UPS involves three enzymes, what are they?

Answer 14

an ATP-dependent ubiquitin-activating enzyme (E1)
ubiquitin-conjugating enzyme (E2)
ubiquitin-protein ligase (E3)

Question 15

The UPS is important in the activation of the ______ ______ pathway and the function of UPS is _______ by ROS

Answer 15

NFκB proinflammatory

modified

Question 16

The ____ ____ is essential for the removal of nitrogen generated via amino acid metabolism; detoxification of ammonia/alanine to _____ in the liver

Answer 16

urea cycle

urea

Question 17

Ammonia is toxic, particularly to the _______; impaired clearance of ammonia can cause ______ ______

Answer 17

CNS

brain damage

Question 18

_______, 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)

Answer 18

heme

Question 19

Heme synthesis-1: glycine and succinyl-coenzyme A condense to form _____________ and this reaction is catalyzed by _______; located in the __________

Answer 19

5-aminolevulinate (5-ALA)
5-ALA synthase
mitochondria

Question 20

The rate limiting step of heme synthesis is the inhibition of _________

Answer 20

5-ALA synthase

Question 21

Heme synthesis-2: In the ________, two molecules of 5-ALA condense to form a molecule containing a pyrrole ring, ______________

Answer 21

cytosol

porphobilinogen (PBG)

Question 22

Heme synthesis-3: Four molecules of PBG combine to form a _______ ______ compound which cyclize to yield ____________ and then __________

Answer 22

linear tetrapyrrole
uroporphyrinogen III
coporphyrinogen III

Question 23

Heme synthesis: Final stages (1 of 2) occur in the _______ where a series of carboxylation/decarboxylation of side chains in uroporphyrinogen III yield _________

Answer 23

mitochondria

protoporphyrin IX

Question 24

Heme synthesis: The last stage is where iron (Fe2+) is added by _________ to _________ to form heme

Answer 24

ferrocheltase

protoporphyrin IX

Question 25

________ 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

Answer 25

bilirubin

Question 26

Bilirubin, when oxidized, reverts to become _______; and this cycle has led to the theory of bilirubin as a cellular ________

Answer 26

biliverdin | antioxidant

Question 27

True or False | Bilirubin is soluble and biliverdin is not

Answer 27

False; biliRUBIN is NOT soluble and biliVERDIN is soluble; bilirubin must be transported by a carrier protein

Question 28

_______ is clinically obvious when plasma bilirubin concentration exceed 50μmol/L; result of an imbalance between production and secretion; there are 3 main causes

Answer 28

jaundice

Question 29

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

Answer 29

prehepatic intrahepatic posthepatic

Question 30

_______ _______ results from excess production of bilirubin as a result of hemolysis, or a genetic abnormality

Answer 30

prehepatic jaundice

Question 31

_______ ______ reflects a generalized hepatocyte disfunction; lack of bilirubin processing; common in newborns

Answer 31

intrahepatic jaundice

Question 32

______ _______ is caused by an obstruction of bilirubin "tree," the plasma bilirubin is conjugated and other biliary metabolites, such as bile acids, accumulate

Answer 32

posthepatic jaundice

Question 33

Metabolism of drugs proceeds in 2 phases: phase 1 --> the addition of a _____ group mediated by _______ phase 2 --> _______ mediated by cytoplasmic enzymes, ______, ______, _____

Answer 33

polar cytochrome C P-450 (CYP) conjugation sulfination, acetylation, methylation

Question 34

Active site of CYP contains a ____ ____ center; important for the ________ of organic substances; accounts for ~75% of total ____ _____

Answer 34

heme iron oxidation drug metabolism

Question 35

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

Answer 35

cytochrome P-450 endoplasmic reticulum allelic variance

Question 36

The commonly prescribed drug _______ can be hepatotoxic in excess; an overdose can cause free radical mediated peroxidation of membrane lipids

Answer 36

acetaminophen

Question 37

Excess intake of ____ ____ remains the most common cause of liver disease in the western world; it can also affect the ubiquitin system

Answer 37

ethyl alcohol

Question 38

________ deaths associated with liver disease in the US annually and _____% of these are linked to alcoholic cirrhosis

Answer 38

25,000 | 40%

Question 39

Ethanol is oxidized in the liver by _____ ________ to form ________

Answer 39

alcohol dehydrogenase | acetaldehyde

Question 40

Acetaldehyde is oxidized by ________ to form ______

Answer 40

``` acetaldehyde dehydrogenase (ALDH) acetate ```

Question 41

______ ______ _____ is the cofactor for the ethanol --> acetaldehyde --> acetate reaction

Answer 41

nicotinamide adenine dinucleotide (NAD+); is reduced to NADH

Question 42

Liver damage in patients who abuse alcohol may arise from the toxicity of _________

Answer 42

acetaldehyde

Question 43

Both alcohol dehydrogenase and acetaldehyde dehydrogenase are susceptible to _____ _____; which can increase/decrease rise of liver disease/alcoholism

Answer 43

genetic polymorphisms | Increase

Question 44

Biochemical tests to measure "liver function" work by testing levels of ______ ______; fluctuations in these can be an indicator of disease

Answer 44

liver enzymes (bilirubin, albumin, etc)

Question 45

____ _____ is a good indicator of liver synthetic function

Answer 45

prothrombin synthesis

Question 46

_______ ______ 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

Answer 46

``` aspartate aminotransferase (AST) alanine amino-transaminase (ALT) ```

Question 47

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

Answer 47

hepatocytes prolonged low

Question 48

An increased level of ________ is indicative of impairment of heme catabolism

Answer 48

Bilirubin

Question 49

A decreased level of _________ is indicative of impaired Carbohydrate metabolism

Answer 49

Glucose

Question 50

An increased level of ______ and a decreases level of ________ is indicative of impairment of Protein synthesis

Answer 50

Prothrombin time | Albumin

Question 51

An increased level of ___________ and a decreased level of __________ is indicative of impairment of protein catabolism

Answer 51

Ammonia | Urea

Question 52

An increase of _______ and ______ is indicative of an impairment of lipid metabolism

Answer 52

Cholesterol | Triglycerides

Question 53

An increase of _________ is indicative of an impairment with drug metabolism

Answer 53

Drug half time

Question 54

An increase in ____ _____ is indicative of an impairment of bile acid metabolism

Answer 54

Bile acids