Biochemistry Of The Liver

Question 1

Liver qualities

Answer 1

. Metabolically active
. Exocrine function: bile
. Capable of regeneration

Question 2

Periportal vs perivenous systems

Answer 2

. Periportal: more O2, more mitochondria, more oxidative metabolism
. Perivenous: less O2, anaerobic metabolism

Question 3

Kupffer cells

Answer 3

. Reticuloendothelial cells

. Macrophage

Question 4

Bilirubin when liver is damaged

Answer 4

. Total bilirubin inc. softly due to direct bilirubin

Question 5

Hepatocellular markers in serum

Answer 5

. Inc. w/ damage
. ALT
. AST

Question 6

Cholestasis/biliary Markers

Answer 6

. Inc. in serum w/ damage
. ALP/ALK
. GGT (induced by alcohol use
. 5’-nucleotidase

Question 7

Hepatic biosynthetic function

Answer 7

. Albumin (dec. when sufficient liver biosynthesis is lost)

. Prothrombin (PT/INR, inc. when function is lost)

Question 8

Detoxification in liver

Answer 8

. Processes waste products 
. Ammonia detoxification 
. Drug metabolism 
. Conjugation of bilirubin 
. Bile acids and salts

Question 9

Biochemicals made and/or stored in liver

Answer 9

. Clotting factors 
. Plasma proteins: serum albumin 
. Cytochrome P450 proteins 
. Vit. D synthesis 
. Fat, cholesterol, lipoprotein biosynthesis 
. Bile acids and salts 
. Stores glucose and iron

Question 10

Albumin

Answer 10

. Half life: 17-20 days
. Non-specific carrier of hydrophobic molecules (FFA, steroids, vit, ADEK
. Carries Ca
. Maintains oncotic pressure (lo levels accompanied w/ edema)
. Low levels indicate poor nutrition
. Replaced at rate of 5% per day

Question 11

Human fuel metabolism is regulated by ____

Answer 11

. Availability of resources

. Hormones present (insulin, glucagon)

Question 12

Insulin is secreted in response to ___

Answer 12

. Inc. blood glucose (most powerful stimulator)
. Inc. AA in blood
. GI hormones (CCK)
. Inhibited by E

Question 13

Glucagon is secreted in response to _____

Answer 13

. Low blood glucose
. Inc. AA in blood
. Inc. E regardless of glucose levels
. Inhibited by inc. blood glucose

Question 14

Consumption of meal high in proteins stimulates the release of ____ and why?

Answer 14

. Both glucagon and insulin

. Prevents hypoglycemia that might result from too much insulin in presence of low dietary glucose

Question 15

T/F insulin levels change more than glucagon levels in response to blood glucose

Answer 15

T

Question 16

Where does glucose in blood come from?

Answer 16

. Dietary
. Glycogen
. Gluconeogenesis

Question 17

Periportal system metabolism in fed state

Answer 17

. Glycogen synthesis from glucose from gluconeogenesis
. Gluconeogenesis stimulated from lactate made from perivenous system
. VLDL assembly
. Beta-oxidation as major source of cell ATP

Question 18

Perivenous system metabolism in fed state

Answer 18

. Anaerobic glycolysis
. Glycogen synthesis from glucose form diet
. VLDL assembly
. Some FA/TAG synthesis

Question 19

Periportal metabolism in intermediate starvation (4-24 hrs)

Answer 19

. Gluconeogenesis
. Glycogen breakdown
. VLDL
. Beta-oxidation as major ATP source

Question 20

Perivenous system metabolism during intermediate starvation (4-24 hrs)

Answer 20

. Anaerobic glycolysis
. Glycogen breakdown
. VLDL assembly

Question 21

Liver metabolism in frank starvation (7-40 days)

Answer 21

. Both periportal and perivenous do same thing 
. Gluconeogenesis and glucose export
. Keatone body formation and export
. Beta-oxidation as major ATP source 
. Glycogen is gone

Question 22

Adaptation in response to ample food supply

Answer 22

. Enzymes for fat are induced (including liver glycolytic enzymes)
. Liver gluconeogenesis enzymes dec.

Question 23

Adaptation in response to starvation

Answer 23

. Gluconeogenesis enzymes inc.
. Aminotransferases, urea cycle enzymes inc. to provide substrates for gluconeogenesis
. Fat biosynthesis enzymes dec.

Question 24

Drug metabolism

Answer 24

. Drugs generally hydrophobic
. Metabolism makes them more hydrophilic the are excreted
. Phase I: detoxification by liver cytochrome P450 proteins
. Phase II: detox by hepatic enzymes by assign glucuronic acid, sulfate group

Question 25

Cytochrome P450 proteins

Answer 25

150+ proteins that have enzyme-bound heme that absorbed light at 450nm
. Use molecular O2 to hydroxylate hydrophobic substrates, making original molecule more soluble
. Each protein has different substrate specificity
. Uses NADPH and O2 to make substrate-OH and H2O
. Found in smooth ER in liver, adrenals, ovaries

Question 26

Cytochrome P450 pathway functions

Answer 26

. Hydroxylations for steroid biosynthesis
. Hydroxylation of drugs
. Goal is detoxification

Question 27

Induction of P450 proteins causes ____ for Drugs

Answer 27

. More hydroxylation and excretion making drugs less therapeutic

Question 28

Inhibition of P450 proteins means what for drugs?

Answer 28

. Dec. breakdown

. Accumulation of drug above therapeutic level can cause side effects

Question 29

Acetominophen in liver

Answer 29

. Phase I and II systems
. Initially metabolized by phase II system by glucuronidation/sulfation to make excreted metabolites
. If this is saturated then phase I is favored
. Phase I uses CYP2E1 is make NAPQI that is hepatotoxic and needs glutathione to make benign product
. If phase I is saturated then toxins will accumulate damaging cell
. Treatment: anti-dote N-acetyl cysteine to prevent damage