Biochem

Question 1

Phase I and II of drug metabolism involve what processes?

Answer 1

Phase I oxidatio;, increased solubility of hydrophobic products

Phase II conjugation; attachment of molecule to increase charge to prevent re-absorption

Question 2

The zones of the hepatic lobule are arranged in what order? Which will be first to be affected by ischemia and why?

Answer 2

Zone are arrange from outside of the lobule toward the central vein as Zone 1 (near triad) and 3 near the central vein.
Zone 3 has least O2 content and will notice ischemic changes first.

Question 3

What is the enterohepatic circulation?

Answer 3

Circulation of bile acids and salts from the duodenum through the terminal ileus (if recycled; 95%), or out with feces otherwise.

Question 4

Bile is secreted into the intestine for what two primary purposes?

Answer 4

Detergent to solubilize dietary lipids

Export oxidized, conjugated waste products such as cholesterol, bilirubin, drugs, and toxins.

Question 5

The liver conjugates many compounds via phase II metabolism. How is this done with bilirubin; why is it done?

Answer 5

Linked to glucuronic acid (UDP-glucuronsyl transferase) through glycosidic linkage to increase its solubility.

Question 6

Bile acid is involved in what type of feedback with CYP7a1? Cholesterol 7 alpha hydroxylase activity would be increased in what circumstances?

Answer 6

Neg feedback

Ileal resection would decrease re-absorption of bile acids and increase the need for cholesterol 7 alpha hydroxylase activity

Question 7

From what molecule to bile acids originate?

Answer 7

cholesterol. They’re oxidized to form acids(pKa close to physiologic) and acids can be converted to bile salts with low pKa

Question 8

How do bile acids work to solubilize fat in the duodenum?

Answer 8

One side of the acid is lipid the other water soluble. The hydrophobic side interacts with the lipid to solubilize it. Fat droplets are surrounded by these acids and are suspended in water as an emulsion.

Question 9

What are the two most common bile acid prefixes?

Answer 9

glyco-and Tauro- cholic acid.

Question 10

What are secondary bile acids and salts; etiology?

Answer 10

These are primary (human metabolized) acids and salts that have been metabolized (reduced) by bacteria in the gut

Question 11

How do you tell the difference (chemically) between bile salts and acids that have been metabolized (reduced) by intestinal bacteria?

Answer 11

Bile salts/acids with a hydroxyl at C7 have undergone human metabolism only, if they lack it, they have undergone bacterial metabolism

Question 12

How does the absorption of bile salts and acids differ, why does it differ?

Answer 12

Bile acids are absorbed along the entire length of the small intestine, but bile salts are preferentially absorbed near the terminal ileum.

This is due to chemical composition: acids are less ionized and can be reabsorbed throughout the small intestine whereas the salts are charged and require a special transporter at the terminal ileum for reabsorption.

Question 13

What is the primary component and color of gall stones?

Answer 13

cholesterol, and yellow

Question 14

Splenic Macrophages have what enzymes to facilitate the conversion of heme into bilirubin?

Answer 14

Heme oxigenase which breaks down heme into Fe 2+, CO, and biliverdin (soluble), and biliverdin reductase which forms bilirubin from biliverdin (insoluble).

Question 15

Bilirubin has what functions in the body? How is it transported in the blood?

Answer 15

Antioxidant and neurotoxin

albumin

Question 16

The direct method of measuring bilirubin measures conjugated bilirubin. How and why is it conjugated, and what enzyme is used?

Answer 16

How: bilirubin is conjugated by adding a glucuronic acid to become bilirubin diglucuronide.

Why: This conjugation increases the solublity of bilirubin prior to its export through the basolateral membrane of the hepatocyte into the bile canaliculi.

Enzyme is UDP glucuronosyl transferase

Question 17

UDP-glucuronosyl transferase is implicated in which types of hyperbilirubinemia/jaundice? What are the common effects of these syndromes?

Answer 17

Gibert syndrome(AD), Crigler Najjar type II, and I (AR)

Increase unconjugated bilirubin /indirect

Question 18

The prehepatic causes of hyperbilirubinemia associated with mutation, or KO, of the UDP glucuronosyl transferase are the result of whay gene mutation?

Answer 18

UGT1A1 which codes for the enzyme

Question 19

Which causes of jaundice increase conjugated bilirubin? Which affects the basolateral membrane and which the apical?

Answer 19

Dubin johnson syndrome (basolateral) and rotor syn (apical)

Question 20

How does an increase in heavy metals interfere with normal cellular function?

Answer 20

They can out compete essential metals for enzymatic binding spots. This is true for an excess of both essential and non essential metals.

ROS and Liver damage

Question 21

What are some clinical presentations of Menke disease?

Answer 21

Neurodegeneration (MOA)
connective tissue disordes b/c need Cu in Collagen
Kinky spare fragile hair
decreased pigment
hypothermia (need Cu in Complex IV ETC)
SOD inactivated-ROS

Question 22

Clinical presentations of wilsons disease?

Answer 22

Copper is Hella BAD

Ceruloplasmin decrease, cirrhosis, corneal deposits (kayser-Fleischer rings), Copper accumulation, and HCC

Hemolytic anemia

Basal ganglia degeneration (parkinsons)
Asterixis
Dementia, Dyskinesia, Dysarthria

Question 23

You look at your patients LFT and notice AST, and ALT present what should you conclude?

Answer 23

Nothing unless they’re elevated above normal. There should be a baseline level of these enzymes due to normal hepatocyte turnover.

Sudden lysis will release large numbers of hepatocytes and is concerning.

Question 24

A number of hepatocytes are damage on the basolateral aspect of the cell surface. Which enzymes will be released confirming the location of cell injury?

Answer 24

ALP, and GGT -alkaline phosphatase and gamma glutamyl transferase. Usually released due to cholestasis and back up of bile in the duct; all the way to the canaliculi between hepatocytes.

Question 25

Lactate dehydrogenase can be release in hepatocellular damage. What’s the normal function of this enzyme? How does ALT participate?

Answer 25

de protonates lactate (oxidation) so it can be converted to pyruvate (while NAD+ is converted to NADH, by accepting this proton). This happens a lot in the liver as it receives lactate from RBC which can only perform glycolysis but can’t run the kreb cycle. This pyruvate is used in gluconeogenesis.

ALT can convert alanine (alpha amino acid) from RBC, into pyruvate (alpha keto acid) for gluconeogenesis as well.

Question 26

What is the location of ALT, AST, and LDH in the hepatocyte? When there is minor damage to the hepatocyte will more ALT or AST be released?

Answer 26

cytosol except most AST is in the mitochondria.

Minor damage to the hepatocyte more ALT will be released b/c of the AST in the mitochondria.

Question 27

WTF is the Cori cycle?

Answer 27

This is where glycolosis is performed in the muscle or RBC to produce lactate, or alanine which is then transported to the liver where gluconeogenesis occurs.

Question 28

What’s the purpose of gamma glutamyl transferase?

Answer 28

Forms one of precursor molecules for glutathione synthesis a major antioxidant that helps to oxidize H2O2 a biproduct of SOD in the ETC; thus decreasing free radicals. They are then reduced by NADPH.

Question 29

How do RBC regenerate NADPH without a mitochondria?

Answer 29

Pentose phosphate pathway

Question 30

Which zone is the periportal zone?

Answer 30

zone one near portal triad.

Question 31

Which zone will have the highest concentration of ALT and why? What about AST?

Answer 31

Zone one b/c it has increased oxygen supply and b/c ALT is involved in gluconeogenesis which requires oxygen it will be more concentrated in these cells and decrease toward zone 3.

AST will be constant throughout the zones.

Question 32

Damage to the pericentral zone will lead to what ration of AST to ALT?

Answer 32

AST higher than ALT