Lipid Biochemistry

Question 1

chylomicrhons

Answer 1

apoB-48, apoC-11, apoE

transports dietary triglycerides

Question 2

VLDL

Answer 2

transports tiglyceride from liver to tissue

apoB100, apoC11, ApoE

Question 3

IDL

Answer 3

VLDL remnants - picks up cholesterol from HDL to become LDL

picked up by liver

ApoE, APoB100

Question 4

LDL

Answer 4

delivers cholesterol into cells

apoB100

uptake by liver and other tissues via LDL receptor (apoB-100 receptor)

Question 5

HDL

Answer 5

picks up cholesterol accumulating in blood vessels

apoA-1

delivers cholesterol to liver via scavenger receptor, shuttles ApoCII and ApoE into the blood

Question 6

LPL

Answer 6

lipoprotein lipase

hydrolyzes the fatty acids from triglycerides carried by chylomicrons and VLDL - is activated by apoC-II

Question 7

ApoB48

Answer 7

found on chylomicrons - attached and reqd for release from epithelial cells into lymphatics

Question 8

apoB100

Answer 8

is added in hepatocytes and mediates release into blood

VLDL, IDL, LDL

Question 9

LCAT

Answer 9

lecithin-cholesterol acytransferase

activated by apoA-1 on HDL, adds fatty acid to cholesterol - allowing HDL to transport cholesterol from periphery to the liver

Question 10

SRB1

Answer 10

scavenger receptors- a way for HDL picked up in periphery to enter cells

Question 11

Type I hypertriglyceridemia

Answer 11

genetic absence of LPL

• dz triglyceride in blood
• see orange-red eruptive xanthomas over mucous membranes and skin

can also be caused by diabetes, alcoholism and G6PD deficiency

Question 12

carnitine problems?

Answer 12

• see greatly elevated amounts of triglycerides w/ primary long chain fatty acids (decreased LCFA metabolism due to lack of carnitine shuttle)
• large number of lipids vacuoles in mm. biopsy
• mm. rely on Fas as long term source of energy

Question 13

sx of carnitine problems?

Answer 13

Symptoms: accumulation of LCFAs in tissues → cardiomyopathy, skeletal mm. myopathy, encephalopathy and impaired liver function, mm. cramping, severe weakness, death
• muscle, kidney and heart tissues are primarily effected
• muscle weakness during prolonged exercise
• mm. necrosis, myoglobulinuria, hypoglycemia, fatty liver

Question 14

causes of carnitine deficiency/

Answer 14

Causes:
• Primary carnitine deficiency: due to inherited CTPI or CPT II deficiency (can be treated by avoiding fasting, dietary restrictions of LCFAs and carnitine supplement)
• liver disease → impaired endogenous synthesis of carnitine
• inadequate intake of carnitine
• carnitine loss due to diarrhea, diuresis, hemodialysis

Question 15

ddx of carnitine deficiency?

Answer 15

Diagnosis:
• based upon pt. very low plasma and mm. carnitine levels
• fasting ketogenesis is impaired
• hypoglycemia, precipitated by fasting/strenuous exercise
• mm. biopsy shows significant lipid vacuoles

Treatment:
• oral carnitine, avoidance of fasting/strenuous exercise, supplementation of medium-chain triglycerides, high-carbohydrate low fat diet

Question 16

systemic primary carnitine deficiency?

Answer 16

Systemic primary carnitine deficiency, (SPCD) also known as carnitine uptake defect, carnitine transporter deficiency (CTD) or systemic carnitine deficiency is an inborn error of fatty acid transport.

Symptoms such as chronic muscle weakness, cardiomyopathy, hypoglycemia and liver dysfunction.
• The first suspicion of SPCD in a patient with a non-specific presentation is an extremely low plasma carnitine level
• Treatment for SPCD involves high dose carnitine supplementation, which must be continued for life

Question 17

CAT-1 or CPT-I deficiency

Answer 17

a rare metabolic disorder that prevents the body from converting certain fats called long-chain fatty acids into energy, particularly during periods without food.
• Symptoms include low levels of ketones and low blood sugar (hypoglycemia).
• People with this disorder typically also have an enlarged liver (hepatomegaly), muscle weakness, and elevated levels of carnitine in the blood.- see liver dysfunction

Question 18

CAT-2 or CPT-II deficiency

Answer 18

a metabolic disorder characterized by an enzymatic defect that prevents long-chain fatty acids from being transported into the mitochondria for utilization as an energy source.
• It is the most common inherited disorder of lipid metabolism affecting the skeletal muscle of adults – mm. weakness and brown urine
• Treatment:High-carbohydrate (70%) and low-fat (<20%) diet to provide fuel for glycolysis; use of carnitine to convert potentially toxic long-chain acyl-CoAs to acylcarnitines

Question 19

xanthomas

Answer 19

• xanthomas are lesions characterized by accumulation of lipid-laden macrophages
• xanthomas develop in altered systemic lipid metabolism or as a results of local cell dysfunction

Question 20

type I hyperlipidemia

Answer 20

: lipoprotein lipase deficiency
• deficiency results in massive accumulation of chylomicrons in plasma
• elevation of triglycerides
• manifests in childhood w/ acute pancreatitis
• see eruptive xanthomas

Question 21

type 2 HL

Answer 21

defective apo-B100 protein
• see accumulation of LDL and VLDL and cholesterol levels variably
• see tendinous xanthomas, tuberous xanthomas, xanthelasmas

Question 22

Type 3 HL

Answer 22

apo-protein E deficiency
• accumulation of IDL, triglycerides and cholesterol levels
• see premature atherosclerosis, plane xanthomas

Question 23

type 4 HL

Answer 23

: hypertriglyceridemia due to overproduction of VLDL
• elevated VLDL, plasma cholesterol levels are normal
• eruptive xanthomas
• associated w/ coronary heart disease, DM type II, obesity, alcoholism

Question 24

type 5 HL

Answer 24

genetic defects in apo-lip C
• accumulations of chylomicrons and VLDL
• severe elevation of triglycerides in plasma
• presents in early childhood with acute pancreatitis, eruptive xanthomas

Question 25

secondary HL?

Answer 25

- Decreased synthesis of HDL: • see increased LDL levels • presents w/ premature CAD, plane xanthomas - Hepatic lipase deficiency: • presents with CAD, xanthomas

Question 26

secondary hypertriglyceridmeia?

Answer 26

- diabetes mellitus, pancreatitis, gout, type 1 glycogen storage disease, alcoholism, oral contraceptives

Question 27

combined hypercholesterol and hyper triglyceridemia?

Answer 27

- nephrotic syndrome, chronic renal failure, steroid immune suppression

Question 28

1. Xanthelasma palpebrarum

Answer 28

- is the most common xanthomas - lesions are soft, velvety, yellow, flat, around the eyelids - associated with hyperlipidemia - secondary to cholestasis

Question 29

Tuberous xanthomas

Answer 29

firm, painless, red-yellow nodules usually develops in pressure areas, extensor surfaces of knees, elbows - associated with hypercholesterolemia and increased levels of LDL - secondary to nephrotic syndrome, hypothyroidism

Question 30

. Tendinous xanthomas

Answer 30

- associated with severe hypercholesterolemia and elevated LDL levels. - lesions often related to trauma - nodules related to tendons or ligaments - secondary to cholestasis

Question 31

Eruptive xanthomas

Answer 31

- erupt as crops of small, red-yellow papules, may spontaneously resolve over weeks - secondary to diabetes

Question 32

Plane xanthomas

Answer 32

- associated with dysbetalipoproteinamia - can occur in any site - covers large areas of face, neck, thorax - secondary to cholestasis

Question 33

statins

Answer 33

• Statins (Lovastatin, atorvastatin, fluvastatin, pravastatin and simvastatin): - efficacious in lowering plasma cholesterol - act as competitive inhibitors of the enzyme HMG-CoA reductase (plays a role in production of cholersterol in liver) - these molecules mimic the structure of the normal substrate of the enzyme (HMG-CoA) and act as transition state analogues - while statins are bound to the enzyme, HMG-CoA cannot be converted to mevalonate, thus, inhibiting the whole cholesterol biosynthesis process

Question 34

Type IIa HL?

Answer 34

Accumulation of LDL Familial LDL receptor deficiency and familial defective apo-B100 Plasma cholesterol levels are elevated Plasma triglyceride levels are normal Manifest severe atherosclerosis May present with: - tendinous xanthomas, or - tuberous xanthomas, as well as, - xanthelasmas

Question 35

type IIb HL?

Answer 35

- accum. of both LDL and VLDL - defective apo-B100 protein - variable elevations of cholesterol and triglycerides may present with: - tendinous xanthomas, tuberous xanthomas, xanthelasmas