Biochem-Cholelithiasis

Front 1

Cholesterol structure explains its ____ water solubility

Back 1

low

Front 2

Cholesterol is derived from both ______ and the _____

Back 2

endogenous synthesis
diet

Front 3

Cholesterol is made from _____.

Back 3

acetyl-CoA

Front 4

Step 2 in the pathway above (_______) is the committed and regulated step of the pathway.

Back 4

HMG-CoA reductase

Front 5

HMG-CoA reductase is feedback-inhibited by _______ at the transcriptional and enzyme levels

Back 5

free cholesterol

Front 6

______ stimulates HMG-CoA reductase.

Back 6

insulin

Front 7

Our bodies contain 140 g of cholesterol, most of it in __________.

Back 7

nervous tissue

Front 8

Dietary cholesterol is esterified by the intestinal mucosal enzyme _______.

Back 8

acyl-CoA-cholesterol acyl transferase (ACAT)

Front 9

Cholesterol is very insoluble in water, but esterified cholesterol is even more insoluble, hence _______ before packaging.

Back 9

esterification

Front 10

After uptake by intestianal brush border cells, half of it, both cholesterol and cholesterol esters are packaged together with dietary triglycerides and lipoprotein into _________.The other half is disposed of with the stool after conversion to neutral sterols by bacteria. nearly 500 mg of unmetabolized cholesterol can be eliminated from the body per day!

Back 10

chylomicrons

Front 11

The stuff in chylomicrons enters the enterohepatic circulation. First chylomicrons deposit their content of tryilycerides to _________ (after broken down to fatty acids by cellular lipoprotein lipase

Back 11

peripheral tissue

Front 12

The remainder of the chylomicron particle is funneled to the ______(requires HDL).

Back 12

liver

Front 13

In the liver, it goes in one of three ways:

Back 13

packaging in VLDL, conversion to bile acids and flow with bile, or direct deposit of cholesterol itself into the bile and from there to intestine again.

Front 14

VLDL is secreted from the liver, remodeled into ____ in the blood

Back 14

LDL

Front 15

The LDL is the primary form of cholesterol that is uptaken by peripheral cells which use it mainly to make their _______.

Back 15

membranes

Front 16

Bile acids are made in the liver and deposited in the ________

Back 16

gallbladder

Front 17

Half of the gallbladder cholesterol is absorbed by the _______.

Back 17

intestine

Front 18

half of the liver’s pool of cholesterol is eventually metabolized to the _______ in the liver.

Back 18

primary bile acids

Front 19

Bile acids are required for absorption of _________ by the intestinal brush border.

Back 19

long-chain fatty acids

Front 20

These primary bile acids are then conjugated with _____ or _____ in the liver to increase their amphipathic nature and miscibility with fatty acids (needed in the intestine) and dumped into the bile, stored in the gallbladder.

Back 20

glycine
taurine

Front 21

The deconjugated bile acids 96% are absorbed by a __________ mechanism in the ileum and returned to the liver. The liver conjugates them secretes them again in the bile.

Back 21

sodium cotransport

Front 22

Upon eating a fatty meal, the gallbladder contracts (via hormonal signal) to release ______ into the intestinal lumen.

Back 22

Bile

Front 23

Intestinal bacteria ______ bile acids in the intestine.

Back 23

Deconjugate

Front 24

________of bile acids are made by the liver. They circulate 5-8 times daily, amounting to 20 g/day of secreted bile acids.

Back 24

0.5 g / day

Front 25

When bile flow is blocked due to gallstones, bile piles up in the liver and seeps to the _____

Back 25

blood

Front 26

Elevated plasma levels of ______is indicative of liver disease or gallstones.

Back 26

bile acids

Front 27

steroid nucleus of cholesterol cannot be degraded in the human body.
Cholesterol has to be disposed of by the biliary system, either as such or after conversion to bile acids. half of the cholesterol is eventually metabolized to ______ in the liver. Conjugation makes them more water soluble.

Back 27

primary bile acids

Front 28

The committing step in bile synthesis is _______and the synthesis is feedback-inhibited by ________.

Back 28

7α-hydroxylase
bile acids

Front 29

This is a monooxygenase reaction and requires molecular____, _____, and _____-.

Back 29

oxygen
NADPH
cytochrome P-450

Front 30

_________also seems to be involved. Deficiency (scurvy) impairs the formation of bile acids and causes cholesterol accumulation and atherosclerosis.

Back 30

Ascorbate

Front 31

Regulation of bile synthesis takes place in four ways:
1. ________ (the product) reduce the level of 7α-hydroxylase by inhibiting the transcription of its gene.
2. _______ (the substrate), in contrast, induces 7α-hydroxylase synthesis transcriptionally.
3. Bile acids also reduce the activity of ______, the enzyme that makes cholesterol. Less cholesterol means less 7a-hydroxylase.
4. _______ induce the synthesis of 7α-hydroxylase. This effect contributes to the increased plasma cholesterol level in patients with hypothyroidism.

These regulatory effects ensure the maintenance of an adequate pool of free cholesterol in the liver.

Back 31

Bile acids
Cholesterol
HMG-CoA reductase
Thyroid hormones

Front 32

Cholesterol precipitates and forms gallstones when bile cholesterol level is too _____, or levels of the emulsifying lipids are too ____

Back 32

high
low

Front 33

Normal composition of bile is at *: ____ molecules of cholesterol for every ___ molecules of lecithin and _____ molecules of bile acid.

Back 33

10
5
85

Front 34

Major bile constituents:

Back 34

lecithin (phosphatidylcholine) as emulsifying lipid, bile acids (in salt form), cholesterol.

Front 35

Gallstones afflict 20% of all people in Western countries, most commonly ____ _____ ______

Back 35

fat, fertile females.

Front 36

10% of gallstones consist of substances other than cholesterol, usually bilirubin and other bile pigments, hence ________

Back 36

“pigment stones.”

Front 37

Symptoms of gallstones (4):

Back 37

severe pain, intolerance for fatty foods, sometimes hyperbilirubinemia, itching due to accumulation of bile salts in the skin.
(2/3 patients with gallstones are asymptomatic).

Front 38

Diagnosis of gallstones

Back 38

ultrasound.

Front 39

Treatement of gallstones:

Back 39

cholecystectomy or oral administration of large amounts of chenodeoxycholic acid (unconjugated bile acid) to solubilize cholesterol.

Front 40

Bile acids are required for absorption of _________ by the intestinal brush border.

Back 40

long-chain fatty acids

Front 41

These primary bile acids are then conjugated with _____ or _____ in the liver to increase their amphipathic nature and miscibility with fatty acids (needed in the intestine) and dumped into the bile, stored in the gallbladder.

Back 41

glycine
taurine

Front 42

The deconjugated bile acids 96% are absorbed by a __________ mechanism in the ileum and returned to the liver. The liver conjugates them secretes them again in the bile.

Back 42

sodium cotransport

Front 43

Upon eating a fatty meal, the gallbladder contracts (via hormonal signal) to release ______ into the intestinal lumen.

Back 43

Bile

Front 44

Intestinal bacteria ______ bile acids in the intestine.

Back 44

Deconjugate