Metabolism 101

Question 1

Long chain fatty acid degradation site

Answer 1

Transport of Fatty Acyl-CoA from the cytosol into the mitochondria (via carnitine shuttle transport)

Question 2

Systemic Primary carnitine deficiency

Answer 2

Inherited defect in transport of Long chain fatty acids into the mitochondria (defect in carnitine shuttle)
Causes weakness, hypotonia and hypoketotic hypoglycemia

Question 3

Fatty acid synthesis rate limiting enzyme

Answer 3

Acetyl CoA carboxylase

Question 4

Fatty acid oxidation rate limiting enzyme

Answer 4

Carnitine acyltransferase I

Question 5

Ketone bodies

Answer 5

Acetone, acetic state and beta hydroxybutyrate

Question 6

Causes of increased ketone body synthesis

Answer 6

Ketoacidosis: oxaloacetate is depleted for gluconeogenesis
Alcoholism: excess NADH shunts oxaloacetate to malate
BOTH PROCESSES–> increased acetyl CoA
Acetyl CoA converted to acetoacetate and beta hydroxybutyrate in liver and delivered to extrahepatic tissues

Question 7

Fuel use after eating: Fed state

Answer 7

Glycolysis and aerobic respiration

Question 8

Fatty acid synthesis site

Answer 8

Transport citrate from mitochondria to the cytosol (via citrate shuttle)
Occurs in liver, lactating mammary glands and adipose tissue

Question 9

Fuel Use: starvation days 1-3

Answer 9

Hepatic glucogenolysis
Adipose release of FFA
Energy use of FFA in muscle and liver
GLYCOGEN IS DEPLETED AFTER ONE DAY OF FASTING

Question 10

Fuel Use: starvation 3+ days

Answer 10

Adipose stores: ketones become the main source of energy for the brain
After adipose is depleted, vital protein is degenerated –>organ failure and death
Excess adipose stores determine length of survival

Question 11

Cholesterol synthesis

Answer 11

Acetyl CoA precursor

Enzyme: HMG CoA reductase

Question 12

Lipoprotein Lipase

Answer 12

Degradation of triglycerides circulating in chylomicrons and VLDL’s
On vascular endothelial surface

Question 13

Hepatic TG lipase

Answer 13

Degradation of TG remaining in IDL

Question 14

Hormone sensitive lipase

Answer 14

Degredation of TG’s stored in adipocytes

Question 15

LCAT

Answer 15

Takes “nascent”/immature HDL and adds cholesterol to it to form a mature HDL particle

Question 16

Cholesterol ester transfer protein (CETP)

Answer 16

Mediates transfer of cholesterol esters to other lipoprotein particles
Takes cholesterol esters from mature HDL, transfers them to VLDL, IDL and LDL in exchange for triglycerides

Question 17

ApoE

Answer 17

Mediates remnant uptake
Chylomicrons, chylomicrons remnant, VLDL, IDL and HDL
EVERYONE (besides LDL) gets ApoE

Question 18

ApoA-I

Answer 18

Activates LCAT

Chylomicrons and HDL

Question 19

ApoC II

Answer 19

Lipoprotein lipase cofactor

Chylomicron, VLDL and HDL

Question 20

ApoB48

Answer 20

mediates chylomicron secretion

Chylomicron/chylomicron remnant

Question 21

ApoB 100

Answer 21

Binds LDL receptor

VLDL, IDL and LDL

Question 22

Familial dyslipidemia type I

Answer 22

Autosomal recessive
LPL or ApoCII deficiency
Increased TG, chylomicrons and cholesterol
Clinical s/s: pancreatitis, hepatosplenomegaly, pruritic xanthomas
Creamy layer of supernatent

Question 23

Familial hypercholesterolemia

Type II

Answer 23

Autosomal dominant
Absent or defective LDL receptors 
Increased LDL, cholesterol 
Heterozygotes: 300 cholesterol 
Homozygous: 700+ (very rare) 
Accelerated atherosclerosis: MI before age 20, tendon xanthomas, corneal arcus

Question 24

Hypertriglyceridemia

Type IV

Answer 24

Autosomal dominant
Hepatic overproduction of VLDL
Increased VLDL, TG
Hypertriglyceridemia–>acute pancreatitis (>1000 for TG’s)

Question 25

Abetalipoproteinemia

Answer 25

Auto recessive
Decreased ApoB48 and ApoB100
MTP mutation
S/s steatorrhea, night blindness, vit deficiency: water soluble
Tx: vitamin E