Metabolism

Question 1

NADPH is a product of the ___ shunt

NADPH is used in: (4)

Answer 1

NADPH is a product of the HMP shunt

1) Anabolic processes (steroid and fatty acid synthesis)
2) Respiratory burst
3) Cytochrome P450 system
4) Glutathione reductase

Question 2

NAD+ is generally used in ________ reactions (breakdown of substances) to carry reducing equivalents away as NADH

Answer 2

Catabolic

Question 3

Answer Hexokinase or glucokinase to the following...
Low Km (higher affinity):
Feedback inhibited by glucose 6-P:
High Vmax:
Induced by insulin:

Answer 3

Low Km (higher affinity): Hexokinase
Feedback inhibited by glucose 6-P: Hexokinase
High Vmax: Glucokinase
Induced by insulin: Glucokinase

Question 4

What steps of glycolysis produce ATP?

Answer 4

1,3 BPG (phosphoglycerate kinase) → 3-PG

PEP (Pyruvate kinase) → Pyruvate

Question 5

Explain the actions of FBPase-2 and PFK-2 during the fasting state and the fed state (they are the same bifunctional enzyme)

Answer 5

Fasting state: ↑ glucagon → ↑ cAMP → protein kinase A →↑ FBPase-2, ↓PFK-2 → Less glycolysis, more gluconeogenesis

Fed state: ↑ insulin → ↓cAMP → ↓protein kinase → ↓FBPase-2, ↑PFK-2 → More glycolysis, less gluconeogenesis

Question 6

What are the components of glycolysis? (Substrates and enzymes)
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Answer 6

Glucose (hexokinase) → glucose 6-phosphate (phosphofructoisomerase) → Fructose-6-phosphate (PFK-1) → Fructose-1-6-bisphosphate (Aldolase B/TPI) → Glyceraldehye-3-P (G3PD) → 1,3-bis-phosphoglycerate (phosphoglycerate kinase) → 3-phosphoglycerate (phosphoglycerate mutase) → 2-phosphoglycerate (enolase) → PEP (pyruvate kinase) → pyruvate

Question 7

How does arsenic affect pyruvate dehydrogenase?

How does exercise affect pyruvate dehydrogenase

Answer 7

Arsenic inhibits lipoic acid

Exercise activates PDH: Increases NAD+/NADH ratio, ↑ADP, ↑Ca2+

Question 8

What pyruvate pathways occur in the mitochondria?

Answer 8

Pyruvate dehydrogenase complex
Pyruvate carboxylase (forms oxaloacetate)

Question 9

Which amino acids are purely ketogenic? (when should these be consumed)

Answer 9

Lysine and leucine (increased intake of ketogenic nutrients as treatment for PDH complex deficiency)

Question 10

When is NADH produced in the TCA cycle? ATP consumed? GTP produced?

Answer 10

NADH: Isocitrate dehydrogenase, alpha-kg-dehydrogenase, malate dehydrogenase
ATP: consumed with citrate synthase
GTP: Succinyl CoA synthetase (post succinyl CoA)

Question 11

What are the electron transport inhibitors (decrease ETC proton gradient and ATP synthesis)?

What does Oligomycin inhibit?

Answer 11

Rotenone, cyanide, antimycin A, CO

Oligomycin inhibits ATP synthase

Question 12

What are the irreversible enzymes of gluconeogenesis?

Answer 12

(Pathway Produces Fresh Glucose)
Pyruvate carboxylase (in mitochondria - activated by acetyl CoA)
PEP carboxykinase (requires GTP) Oxaloacetate → PEP
F-1,6-BP (increased by citrate)
Glucose-6-phosphatase (in ER) Glucose-6-P → Glucose

Question 13

What is produced in the oxidative step of the HMP shunt?

Answer 13

CO2, 2NADPH, Ribulose 5-P (enzyme: G6P dehydrogenase)

Question 14

What is produced in the nonoxidative part of the HMP shunt?

Answer 14

Ribose-5-P (DNA synthesis), G3P, F6P (Phosphopentose isomerase transketolases (require B1))

Question 15

What is the blue-green heme containing pigment that gives sputum its color? (It is also an enzyme in the respiratory burst)

Answer 15

Myeloperoxidase (forms HOCl)

Question 16

What is lactoferrin?

Answer 16

A protein found in secretory fluids and neutrophils that inhibits microbial growth via iron chelation

Question 17

Glucose-6-phosphate dehydrogenase deficiency
Inheritance:
Relation to hemolytic anemia:
Characteristic cells:

Answer 17

Inheritance: X-linked recessive disorder
Relation to hemolytic anemia: NADPH is necessary to keep glutathione reduced, which in turn detoxifies free radicals and peroxides which damage RBCs leading to hemolytic anemia
Characteristic cells: Heinz bodies (oxidized Hb), Bite cells

Question 18

Why is fructose intolerance (aldolase B deficiency) worse than essential fructosuria (fructokinase defect)?

Answer 18

Fructosuria: Benign, asymptomatic condition, since fructose is not trapped in cells
Fructose intolerance: Fructose-1-P accumulates, causing decrease in available phosphate (fructokinase uses ATP) resulting in inhibition of glycogenolysis and gluconeogenesis

Question 19

What enzyme is absent in classic galactosemia? What causes damage?

Answer 19

Galactose-1-phosphate uridyltransferase - damage cuased by accumulation of toxic substances (galacitol)

Question 20

What are the essential amino acids?

Answer 20

Glucogenic: methionine, valine, histidine
Glucogenic/Ketogenic: Isoleucine, phenylalanine, threonine, tryptophan
Ketogenic: Leucine, lysine

Question 21

What are the substrates of the urea cycle?

What are the enzymes?

Answer 21

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Ornithine (ornithine transcarbamylase) → Citrulline + Aspartate (arginosuccinate synthetase) → Arginosuccinate (Arginosuccinase) → Fumarate (TCA) and Arginine (Arginase) → Urea (to kidney)

Question 22

How is the excess nitrogen (NH3) from amino acid catabolism included into the urea cycle?

What provides the second nitrogen group to urea?

Answer 22

CO2 + NH3 (Carbamoyl phosphate synthetase I + N-acetylglutamate) → Carbamoyl phosphate + Ornithine (Ornithine transcarbamylase) → Citrulline

Aspartate provides the second nitrogen group

Question 23

How do glutamate and alanine help remove ammonia from amino acid catabolism?

Answer 23

Amino acids (NH3) + alpha-KG → Glutamate (NH3) → Alanine (NH3) → Alanine cycle (muscle → liver) → Glutamate (NH3) → Urea

Question 24

How does the Cori cycle contribute to transport of ammonia by alanine and glutamate?

Answer 24

Takes the pyruvate in the liver that remains from transfer of alanine NH3 to glutamate and converts it to glucose, then moves it back to the muscle and turns it back into pyruvate for re-use

Question 25

What is the difference in presentation between N-acetylglutamate deficiency and Ornithine transcarbamylase deficiency?

Answer 25

N-acetylglutamate deficiency: Hyperammonemia characterized by increased ornithine with normal urea cycle enzymes Ornithine transcarbamylase deficieny (X-linked recessive): Excess carbamoyl phosphate is converted to orotic acid → increased orotic acid in blood and urine, decreased BUN

Question 26

What disorder occurs with a tyrosinase deficiency? What enzyme is deficient in PKU? What enzyme is deficient in alkaptonuria?

Answer 26

Albinism: DOPA (tyrosinase) → Melanin PKU: Phenylalanine hydroxylase (or BH4) (Phenylalanine → Tyrosine) Alkaptonuria: Homogentisate oxidase (Homogentisate → Maleylacetoacetic acid → fumarate)

Question 27

What are the two pathways of homocysteine?

Answer 27

1) Homocysteine (cystathionine synthase) → cystathionine → Cysteine 2) Homocysteine (homocysteine methyltransferase) → Methionine

Question 28

What cannot be transported due to cystinuria? What can this lead to? How is it treated?

Answer 28

What cannot be transported due to cystinuria? - COLA: Cysteine, Ornithine, Lysine, Arginine What can this lead to? - Hexagonal cystine stones How is it treated? - After nitroprusside test - potassium citrate, acetazolamide

Question 29

___________ cleaves glucose-1-p residues off branched glycogen until 4 remain before a branch point, then ________ moves three glucose-1-Ps from the branch to the linkage. Then, ________ cleaves off the last glucose-1-P on the branch

Answer 29

Glycogen phosphorylase cleaves glucose-1-p residues off branched glycogen until 4 remain before a branch point, then de-branching enzyme (4-alpha-D-glucanotransferase) moves three glucose-1-Ps from the branch to the linkage. Then, alpha-1,6-glucosidase cleaves off the last glucose-1-P on the branch

Question 30

What is similar and what is different between Niemann Pick disease and Tay-Sachs disease?

Answer 30

Similar: Both consist of progressive neurodegeneration, cherry red spot on macula and are autosomal recessive Different: NPD has foam cells and hepatosplenomegaly whereas TS has lysosomes with onion skin and no hepatosplenomegaly

Question 31

What lysosomal storage disease consists of peripheral neuropathy, developmental delay, optic atrophy and globoid cells? What enzyme is deficient?

Answer 31

Krabbe disease Galactocerbrosidase

Question 32

What disease presents with a deficiency of arylsulfatase?

Answer 32

Metachromatic leukodystrophy

Question 33

Hunters syndrome is Hurlers syndrome + _________ and without _________

Answer 33

Hunters syndrome is Hurlers syndrome + aggressive behavior and without corneal clouding

Question 34

What shuttles fatty acids out of the cytoplasm and into the mitochondria for degradation? What happens if it is deficient?

Answer 34

Carnitine shuttle Inability to transport LCFAs into the mitochondria resulting in toxic acumulation

Question 35

In starvation, glycogen reserves are depleted after __ days What maintains glucose levels after this?

Answer 35

1 day Adipose release of FFA Muscle and liver shift fuel use from glucose to FFA Hepatic gluconeogensis from peripheral tissue lactate and alanine and adipose tissue glycerol and propionyl CoA

Question 36

``` What is the function of each of the following enzymes: Pancreatic lipase: Lipoprotein lipase: Hepatic lipase: Hormone sensitive lipase: LCAT: CETP: ```

Answer 36

Pancreatic lipase: degradation of dietary TG Lipoprotein lipase: Degradation of TG circulating in chylomicrons and VLDL (found on vascular endothelial surfaces) Hepatic lipase: Degradation of TG remaining on IDL Hormone sensitive lipase: Degradation of TG stored in adipocytes LCAT: Catalyzes esterification of cholesterol CETP: Transfer of cholesterol esters to other lipoprotein particles

Question 37

Which apolipoprotein activates LCAT? Which apolipoprotein binds the LDL receptor? Which is an LPL co-factor?

Answer 37

Which apolipoprotein activates LCAT? - A-1 (HDL) Which apolipoprotein binds the LDL receptor? - B-100 Which is an LPL co-factor? - C-II