Biochem Exam 4: Cholesterol

Front 1

What are some of the normal function of cholesterol?

Back 1

Component of cell membranes, necessary for making bile acid, vitamin D, and steroid hormones

Front 2

What are the starting materials for cholesterol synthesis?

Back 2

Acetyl CoA, requires ATP, NADPH

Front 3

What are the products of cholesterol synthesis?

Back 3

Cholesterol, ADP, NADP+

Front 4

Where does cholesterol synthesis occur?

Back 4

Hepatocytes

Front 5

What is the regulatory enzmye in cholesterol synthesis?

Back 5

HMG-CoA Reductase

converts Acetyl-CoA to Mevalonate

Front 6

How is HMG CoA reductase regulated by insulin/glucagon?

Back 6

glucagon and low ATP activate AMP-activated protein kinase & phosphorylate HMG-CoA reductase, inhibiting it

insulin activates phosphatase, dephosphorylating HMG-CoA reductase, activating it

Front 7

When does proteolysis of HMG CoA reducatase increase?

Back 7

proteolysis of HMG CoA reductase increases when cholesterol and bile acid conc are high and they bind to it

Front 8

What induces/represses synthesis of HMG CoA reductase?

Back 8

Synthesis is induced/repressed with levels of cholesterol

Front 9

How do extrahepatic cells receive cholesterol?

Back 9

From LDL from liver. Synthesis of cholesterol is not typically done by extra hepatic cells.

Front 10

How is cholesterol stored in cells?

What enzyme synthesizes this compound?

Back 10

As a cholesterol ester

ACAT (Acyl-CoA cholesterol acytransferase)

Front 11

How is HMG-CoA reductase regulated at the level of transcription?

Back 11

1. SCAP-SREBP complex transloactes from ER to golgi when cholesterol is low (SCAP binds/senses cholesterol levels)
2. SREBP (sterol regulatory element binding protein) is cleaved from complex by S1P & S2P
3. SREBP translocates to nucleus & binds to SRE (sterol regulatory element), activating transcription of HMG-CoA reductase gene

Front 12

How is the expression of the HMG-CoA reductase gene inhibited?

Back 12

high cholesterol prevents cleavage of SREBP from SCAP-SREBP complex and thus prevents activation

low choesterol allows SREBP cleavage, SREBP then travels to nucleus and activates transcription of gene

Front 13

How do statin drugs lower cholesterol?

Drinking grapefruit w/ these drugs could lead to what?

Back 13

inhibition of HMG-CoA reductase
*esp decrease LDL

myopathy & rhabdomyolysis, increases levels of drug

Front 14

How does circadian rhythm effect cholesterol biosynthesis?

Back 14

synthesis peaks 6 hrs after sunset (midnight/sleep)

synthesis is lowest 6 hrs after light (noon/wake)

Front 15

T or F? HMG CoA reductase is not regulated by esterfied cholesterol.

Back 15

True

Front 16

T/F Sterol rings can be degraded by humans

Back 16

FALSE
they CANNOT be degraded must be excreted as bilary cholesterol or bile acids

Front 17

Where is bile salt/acid synthesized?

Back 17

Hepatocytes

Front 18

What are the starting materials for bile salt/acid?

Back 18

Cholesterol, ATP, and NADPH

Front 19

What is the control step in bile acid synthesis?

Back 19

7-alpha-hydroxcholesterol from cholesterol is feedback inhibited by bile salt levels

*via 7-alpha-hydroxylase

Front 20

What are the 4 major components of bile?

Back 20

bile acids, cholesterol, lipids, & bilirubin

Front 21

What are bile acid sequestrants used for?

Back 21

lower cholesterol by decreasing bile acid reabsorption in the gut

Front 22

What are primary conjugated bile salts produced with?

Back 22

bile salt with glycine or taurine

Front 23

how can primary conjugated bile salts be converted to secondary bile salts?

Back 23

by intestinal bacteria

Front 24

-Which lipoproteins are associated with higher risk for CVD?

Back 24

LDL and TG

Front 25

Which lipoproteins are associated with lower risk for CDV?

Back 25

HDL

Front 26

Describe the structure of a lipoprotein

Back 26

Phospholipid sphere with apoproteins on surface. Inside there is TG and cholesterol.

Front 27

Relate protein/lipid ratio to the various lipoproteins

Back 27

VLDL and LDL have low protein to lipid ratios
HDL had high protein to lipid ration

Front 28

What do chylomicrons do?

Back 28

Transport dietary lipids in fed state, NOT synthesized by liver

Front 29

Which proteins does HDL transfer to nacent chylomicrons?

Back 29

Apo E and Apo C2

Front 30

What do Apo E and Apo C2 activate repectaviely?

Back 30

Apo E activates hepatic receptors
Apo C2 activates lipoprotein lipase

Front 31

Chylomicrons are transported to:

Back 31

Adipose and skeletal muscle where lipoprotein lipase converts TG to FA and glycerol

Front 32

-What are chylomicron remenants?

Back 32

Chylomicrons minus TG
They have cholesterol and go to liver

Front 33

*Differentiate between the primary (Conn's disease) and secondary cause of hyperaldosteronism.

know symptoms

Back 33

Causes:
Primary/Conn's= aldosterone-secreting tumor
Secondary= kidney or liver disease (more common)

Symptoms:
hypertension, hypokalemia, alkalosis, fatigue, hypernatremia, polyuria, and headache

Front 34

*Causes and symptoms of Primary adrenal insufficiency (Addison's disease)

Back 34

Causes:
insufficient aldosterone & cortisol due to atrophy of adrenal gland (autoimmune disorder, tuberculosis)

Symptoms:
hypotension, muscular weakness, fever, fatigue, diarrhea, headache, sweating, hypoglycemia, dehydration, weight loss, and nausea

Front 35

*Causes and symptoms of Secondary adrenal insufficiency

Back 35

Causes:
not enough production of ACTH
(abrupt discontinue of taking synthetic glucocorticoids)

Symptoms:
hypotension, muscular weakness, fever, fatigue, diarrhea, headache, sweating, hypoglycemia, dehydration, weight loss, and nausea

Front 36

*Causes and symptoms of Cushing's syndrome

Back 36

Causes:
exogenous is caused by administration of glucocorticoids
endogenous is cuased by excessive production of cortisol due to pituitary or adrenal adenoma

symptoms:
weight gain, sweating, hypertension, & polyuria

Front 37

*Causes and symptoms of Androgen Insensitivity syndrome

Back 37

Causes:
mutations in androgen receptor gene in insensitivity of tissues to androgens

Symptoms: XY female

Front 38

PFIC-1 (Byler disease)
mutated gene:
effect:

Back 38

mutated gene: ATPase FIC-1
effect: phospholipid translocation across membrane, expressed in intestine

Front 39

PFIC-2
mutated gene:
effect:

Back 39

mutated gene: bile salt exporter pump (BSEP)
effect: retention of bile salts w/i hepatocytes & cholestasis

Front 40

PFIC-3
mutated gene:
effect:

Back 40

mutated gene: multidrug resistance protein 3 (MDR3)/ floppase
effect: lack of phosphatidylcholine in bile, free bile acids damage bilary epithelium causing cholangitis

Front 41

Common symptoms for all PFIC (progressive familial intrahepatic cholestatis) diseases

Back 41

symptoms present in early childhood, jaundice, cholestasis, failure to thrive, & intense pruritus

Front 42

Causes of bile salt malabsorption (4)

Back 42

Crohn's disease
celiac disease
overproduction of bile salt
chronic pancreatitis
(high conc of bile acids stimulates water secretion & chronic diarrhea)

Front 43

Cholesterol stones account for 80% of gallstones and form when the cholesterol/phospholipids + biles salts ratio is more than ________

Back 43

1:1

Front 44

when does the kidney produce renin?

Back 44

decreased BP
decreased NaCl in ultafiltrate of the nephron
sympathetic nervous system activity

Front 45

What is the effect of Angiotensin II?

Back 45

stimulates vasoconstriction and thirst reflex

Front 46

what is the effect of aldosterone?

Back 46

stimulates sodium intake
increases BP

Front 47

What does cholesterol esterase (cholesterol ester lipase) do?

how is it regulated?

Back 47

removes ester from cholesterol, increases concentration of free cholesterol
(part of cortisol synthesis)

regulated on level of posttranslational modification, cAMP --> PKA --> phosphorylation = activation

Front 48

What does steroidogenic acute regulatory protein (StAR) do?

how is it regulated?

Back 48

moves cholesterol from outer to inner mitochondrial membrane
(cortisol synthesis)

regulation dependent of cell type, stimulated by LH, ACTH, Angiotensin II

Front 49

What is the rate limiting step of cortisol synthesis and what enzyme is involved?

how is it regulated?

Back 49

pregnenolone produced from cholesterol via desmolase (cholesterol side chain cleavage enzyme)

regulated on level of transcription, contains CRE, cAMP binding to CRE increases expression

Front 50

* Where does the first and rate limiting step, cholesterol---> pregenolone, occur?

Back 50

mitochondria

Front 51

*Where does, the final aldosterone product of cholestrol occur?

Back 51

mitochondria

Front 52

*where does the synthesis of the final cortisol product from cholesterol occur?

Back 52

mitochondria

Front 53

*in contrast, the final androgen and estrogen products of cholesterol of synthesized where?

Back 53

cytosol

Front 54

*What enzyme converts testosterone to estradiol?

Back 54

CYP 19: Aromatase

Front 55

* Angiotensin II stimulates the enzyme involved in the production of what?

Back 55

18-oxydase
produces aldosterone from 18-hydroxy-corticosterone

Front 56

* 21-alpha-hydroxylase deficiency
leads to?
results in?
phenoytype?

Back 56

*most common form of congenital adrenal hyperplasias (CAH), may be partial or complete deficiency

leads to: partial (classic) or complete (non-classic) absence of mineralcorticoids & gluccocorticoids

results in: excess progesterone results in overproduction of androgens (testosterone & estradiol)

phenotype: varies based on classic or non-classic, causing masculinization of external genitalia in females & early virilization in males

Front 57

Negative affects of anabolic steroid hormones in men & women

Back 57

men: headaches, baldness, breast development, reduced sperm, enlarged prostate, testicle shrinkage

women: breast shrinkage, enlarged clitoris, increased face & body hair, deepened voice, menstrual problems

*men & women: face & body acne, strokes/blood clots, high BP, heart disease, nausea, bloating, impotence, liver damage, mood swings, GI problems, aching joints, aggression, tendon injury

Front 58

First step of vitamin D syntheis

Back 58

in skin:
UV light cleaves 7-dehydrocholesterol
-->cholecalciferol (vitamin D3)

Front 59

*Final, rate-limiting step of vitamin D synthesis


What hormone upregulates (+) this step?\
what inhibits this step?

Back 59

in kidney:
25(OH)D3 ----> calcitrol (active vitamin D)
via 1 alpha-hydroxylase

(+): parathyroid hormone (PTH)
(-): active vitamin D (negative feedback)

Front 60

Causes of Vitamin D Deficiency?

Back 60

-inadequate sunlight exposure
-disorders of vitamin D absorption
-certain disorders of liver & kidney

Front 61

Risk factors for Vitamin D deficiency:

Back 61

-age
-malnutrition
-obesity
-sunscreen/excessive clothing
-darker skin color

Front 62

Diseases associated w/ vitamin D deficiency:

Back 62

Rickets: impeded growth, bone deformity
Osteomalacia: bone thinning
Osteoporosis: reduced bone mineral density
(inverse correlation w/ some cancer)

-muscle acnes & weakness

Front 63

How are free hormones transferred through plasma?

Back 63

1. endocrine cell produces free hormone
2. free hormone binds to carrier protein to be transported through plasma w/o being degraded
3. free hormone cleaved from carrier protein
4. free hormone binds to nuclear hormone receptor, biological effects are induced

Front 64

What are sterioid hormones produced from?

where are they produced?

Where does the first enzymatic reaction occur?

Where does the final step of cortisol & aldosterone synthesis occur?

Back 64

cholesterol

many tissues (adrenal cortex & gonads)

mitochondria

mitochondria

Front 65

Where does inactivation of steroid hormone occur?

How does it occur?

How are inactivated hormones excreted?

Back 65

mainly in liver

occurs through adding a double bond (reduction) & conjugation (oxidization, makes more water soluble)

excreted mostly in urine, also via bile