GI & Liver metabolism I&II

Question 1

xenobiotics

Answer 1

taking things in from the outside that are not part of your everyday routine
-ex. drugs, poisons

Question 2

how does acetyl CoA get into the cytosol?

Answer 2

binds to OAA –> convert to citrate –> enter cytosol and broken down by citrate lyase to OAA and acetyl CoA –> start making FAs

Question 3

Acetyl CoA

Answer 3

2C units

contains CoA - made from vit. B5 (pantothenic acid)

Question 4

ACC (acetyl CoA carboxylase)

Answer 4

rate limiting

• starts FA synthesis
• activated by energy and citrate –> adds CO2 to acetyl CoA to make malonyl CoA
• deactivated by long chain FAs
• AMP-kinase (low energy) turns off through phosphorylation
• also short term regulation of TAG synthesis

Question 5

biotin (vit. B7)

Answer 5

needed for most carboxylase enzymes

Question 6

FA synthesis

Answer 6

• add 2C additions (acetyl groups) with fatty acid synthase –> 16C product
• anabolic process - requires reducing equivalents –> NADPH in cytosol

Question 7

beta oxidation

Answer 7

• FAs enter mitochondria through carnitine shuttle

- inhibit CPT1 with malonyl CoA –> prevent FAs from entering mitochondria

Question 8

how do you make TAGs?

Answer 8

FAs are esterified to glycerol

• liver - make glycerol3P from glycerol kinase or DHAP
• adipocytes - make glycerol3P if it is well fed and running glycolysis; NO glycerol kinase
• dehydration synthesis rxn

Question 9

ChREBP (carbohydrate response element binding protein)

Answer 9

long term regulation of TAG synthesis

• activated by carbs to transcribe genes that make FAs (ex. FA synthase or ACC)
• inhibited by AMP & PKA

Question 10

hormone sensitive lipase

Answer 10

breaks down (hydrolyzes) TAGs into free FAs and glycerol

• free FAs transported in blood to tissue by albumin
• glycerol goes to liver for gluconeogensis

Question 11

how do you form ketone bodies?

Answer 11

2C acetyl groups –> 4C acetoacetate –> broken down into acetone or 3-hydroxybutyrate

• increased in fasting, carb restrict diets, or starvation
• production spares glucose

Question 12

what happens if ketone body production is greater than use?

Answer 12

ketonuria or ketonemia

-can cause diabetic ketoacidosis –> pH can decrease

Question 13

function of lipoproteins

Answer 13

transport fat throughout body

• chylomicrons - least dense
• HDL - most dense

Question 14

how are most of the TAGs broken down?

Answer 14

pancreatic lipases

Question 15

formation of bile salts

Answer 15

cholesterol –> 7alpha hydroxylase –> 7 hydroxycholesterol –> chenodeoxycholic acid or cholic acid

Question 16

function of bile salts

Answer 16

• interact with FAs to form micelles
• emulsifying agents
• increase water solubility through conjugation of glycine or taurine in liver

Question 17

mutation in 7 alpha hydroxylase enzyme

Answer 17

bile acid/salt disorder

• no bile salts –> no micelles –> poor fat absorption –> fatty stool
• cannot form bile salts –> build up cholesterol –> gallstones

Question 18

role of CCK

Answer 18

• slow motility of stomach
• increase pancreatic enzymes
• GB contraction to release bile

Question 19

role of secretin

Answer 19

-pancreatic release of bicarb to neutralize stomach acidity

Question 20

bile salt deficiency disorder

Answer 20

making cholesterol faster than being converted into bile salts
-take oral bile salts (chenodeoxycholic acid) for treatment

Question 21

what is needed for chylomicrons

Answer 21

ApoB48

• cholesterol on the inside, PLs on the outside
• TAG loading requires MTP to dock with ApoB48 or 100
• deficient MTP –> abetalipoproteniemia

Question 22

role of lipoprotein lipase

Answer 22

found in the tissues

• activated by ApoCII to release FAs from chylomicrons
• FAs enter tissue
• glycerol goes back to liver

Question 23

phase 1 liver detox rxn

Answer 23

fat soluble toxins

• cytochrome p450 enzymes
• try to make more water soluble
• substrate for phase 2

Question 24

phase 2 liver detox rxn

Answer 24

water soluble toxins

• conjugation pathway –> sulfation, glucoronidation, GSH
• excreted as waste

Question 25

acetominophin toxicity

Answer 25

metabolized by CYTp450 enzymes --> glucoronidation and sulfation - detoxed by GSH - alcohol --> reduces GSH leading to toxicity - treat with n-acetylcystein (NAC) to boost GSH

Question 26

function of cholesterol

Answer 26

- membrane fluidity - forms bile salts and vitamin D - precursor for steroids - come from diet or synthesis in liver --> synthesized in cytosol w/ a lot of reducing equivalents - 1/3 free in blood, 2/3 bound to lipoproteins (linoleic acid)

Question 27

cholesterol absorption

Answer 27

- absorbed by intestinal micelles --> Niemann Pick C1 - inhibited by ezetimibe to lower cholesterol - plant sterols excrete cholesterol in enterocytes

Question 28

where do all Carbons come from during cholesterol synthesis?

Answer 28

acetyl CoA | -HMG-CoA --> mevalonate by HMG-CoA reductase (rate limiting step)

Question 29

regulation of cholesterol synthesis

Answer 29

regulated by phosphorylation - AMP, glucagon, sterols --> inactivate HMG-CoA reductase - insulin, thyroid hormone, high ATP --> activate HMG-CoA reductase

Question 30

what is the 5C unit of cholesterol?

Answer 30

dimethylallyl pyrophosphate | -formed from mevalonate

Question 31

squalene synthase

Answer 31

catalyzes rxn from farnesyl pyrophosphate to squalene | -uses a lot of NADPH

Question 32

function of statins

Answer 32

mimic HMG-CoA substrate for HMG-CoA reductase enzyme --> competitive inhibitor -transition state analog

Question 33

cholesterol and bile acids

Answer 33

- cholesterol --> primary bile acids (more water soluble through hydroxylation) - emulsification - bacteria deconjugate primary to secondary - liver conjugates bile acids with glycine or taurine --> more water soluble and ionized

Question 34

ingested cholesterol transport from enterocyte

Answer 34

-taken up by chylomicrons (use ApoB48) --> lymphatics, thoracic duct, left subclavian

Question 35

cholesterol transport from liver

Answer 35

-taken up by VLDL and LDL (use Apo100)

Question 36

ApoB gene

Answer 36

makes ApoB48 and ApoB100 | -deficiency --> abetalipoproteinemia

Question 37

nonalcoholic fatty liver disease (hepatic steatosis)

Answer 37

imbalance b/w hepatic TAG synthesis and VLDL secretion

Question 38

what shuttles cholesterol to liver or to peripheral tissues?

Answer 38

LDL

Question 39

role of cholesterol ester transfer protein (CETP)

Answer 39

takes TAG from VLDL to put on HDL with the exchange of cholesterol - VLDL forms LDL - do this bc HDL removes cholesterol from periphery (lowering risk for atherosclerosis)

Question 40

function of HDL

Answer 40

uses ApoA1 along with ApoC and ApoE | -reverse cholesterol transport --> take cholesterol from tissues back to liver

Question 41

LCAT

Answer 41

used to add ester to cholesterol to put it into chylomicron core - make more room on outside for more cholesterol binding -activated by ApoA1 on HDL

Question 42

ABCA1 protein

Answer 42

used to help add cholesterol to HDL in the tissues

Question 43

function of bile salts and fiber on cholesterol

Answer 43

lowers absorption of cholesterol by binding to and excreting it

Question 44

phosphorylation

Answer 44

anabolic pathways --> turns off | catabolic pathways --> turns on

Question 45

how is cholesterol regulated

Answer 45

long term by sterol response element (SRE) and sterol response element binding protein (SREP) --> controls expression of HMG CoA reductase expression