Metabolism Flashcards
NADPH is a product of the ___ shunt
NADPH is used in: (4)
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
NAD+ is generally used in ________ reactions (breakdown of substances) to carry reducing equivalents away as NADH
Catabolic
Answer Hexokinase or glucokinase to the following... Low Km (higher affinity): Feedback inhibited by glucose 6-P: High Vmax: Induced by insulin:
Low Km (higher affinity): Hexokinase
Feedback inhibited by glucose 6-P: Hexokinase
High Vmax: Glucokinase
Induced by insulin: Glucokinase
What steps of glycolysis produce ATP?
1,3 BPG (phosphoglycerate kinase) → 3-PG
PEP (Pyruvate kinase) → Pyruvate
Explain the actions of FBPase-2 and PFK-2 during the fasting state and the fed state (they are the same bifunctional enzyme)
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
What are the components of glycolysis? (Substrates and enzymes)
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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
How does arsenic affect pyruvate dehydrogenase?
How does exercise affect pyruvate dehydrogenase
Arsenic inhibits lipoic acid
Exercise activates PDH: Increases NAD+/NADH ratio, ↑ADP, ↑Ca2+
What pyruvate pathways occur in the mitochondria?
Pyruvate dehydrogenase complex Pyruvate carboxylase (forms oxaloacetate)
Which amino acids are purely ketogenic? (when should these be consumed)
Lysine and leucine (increased intake of ketogenic nutrients as treatment for PDH complex deficiency)
When is NADH produced in the TCA cycle? ATP consumed? GTP produced?
NADH: Isocitrate dehydrogenase, alpha-kg-dehydrogenase, malate dehydrogenase
ATP: consumed with citrate synthase
GTP: Succinyl CoA synthetase (post succinyl CoA)
What are the electron transport inhibitors (decrease ETC proton gradient and ATP synthesis)?
What does Oligomycin inhibit?
Rotenone, cyanide, antimycin A, CO
Oligomycin inhibits ATP synthase
What are the irreversible enzymes of gluconeogenesis?
(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
What is produced in the oxidative step of the HMP shunt?
CO2, 2NADPH, Ribulose 5-P (enzyme: G6P dehydrogenase)
What is produced in the nonoxidative part of the HMP shunt?
Ribose-5-P (DNA synthesis), G3P, F6P (Phosphopentose isomerase transketolases (require B1))
What is the blue-green heme containing pigment that gives sputum its color? (It is also an enzyme in the respiratory burst)
Myeloperoxidase (forms HOCl)
What is lactoferrin?
A protein found in secretory fluids and neutrophils that inhibits microbial growth via iron chelation
Glucose-6-phosphate dehydrogenase deficiency
Inheritance:
Relation to hemolytic anemia:
Characteristic cells:
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
Why is fructose intolerance (aldolase B deficiency) worse than essential fructosuria (fructokinase defect)?
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
What enzyme is absent in classic galactosemia? What causes damage?
Galactose-1-phosphate uridyltransferase - damage cuased by accumulation of toxic substances (galacitol)
What are the essential amino acids?
Glucogenic: methionine, valine, histidine
Glucogenic/Ketogenic: Isoleucine, phenylalanine, threonine, tryptophan
Ketogenic: Leucine, lysine
What are the substrates of the urea cycle?
What are the enzymes?
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Ornithine (ornithine transcarbamylase) → Citrulline + Aspartate (arginosuccinate synthetase) → Arginosuccinate (Arginosuccinase) → Fumarate (TCA) and Arginine (Arginase) → Urea (to kidney)
How is the excess nitrogen (NH3) from amino acid catabolism included into the urea cycle?
What provides the second nitrogen group to urea?
CO2 + NH3 (Carbamoyl phosphate synthetase I + N-acetylglutamate) → Carbamoyl phosphate + Ornithine (Ornithine transcarbamylase) → Citrulline
Aspartate provides the second nitrogen group
How do glutamate and alanine help remove ammonia from amino acid catabolism?
Amino acids (NH3) + alpha-KG → Glutamate (NH3) → Alanine (NH3) → Alanine cycle (muscle → liver) → Glutamate (NH3) → Urea
How does the Cori cycle contribute to transport of ammonia by alanine and glutamate?
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
What is the difference in presentation between N-acetylglutamate deficiency and Ornithine transcarbamylase deficiency?
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
What disorder occurs with a tyrosinase deficiency?
What enzyme is deficient in PKU?
What enzyme is deficient in alkaptonuria?
Albinism: DOPA (tyrosinase) → Melanin
PKU: Phenylalanine hydroxylase (or BH4) (Phenylalanine → Tyrosine)
Alkaptonuria: Homogentisate oxidase (Homogentisate → Maleylacetoacetic acid → fumarate)
What are the two pathways of homocysteine?
1) Homocysteine (cystathionine synthase) → cystathionine → Cysteine
2) Homocysteine (homocysteine methyltransferase) → Methionine
What cannot be transported due to cystinuria?
What can this lead to?
How is it treated?
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
___________ 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
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
What is similar and what is different between Niemann Pick disease and Tay-Sachs disease?
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
What lysosomal storage disease consists of peripheral neuropathy, developmental delay, optic atrophy and globoid cells?
What enzyme is deficient?
Krabbe disease
Galactocerbrosidase
What disease presents with a deficiency of arylsulfatase?
Metachromatic leukodystrophy
Hunters syndrome is Hurlers syndrome + _________ and without _________
Hunters syndrome is Hurlers syndrome + aggressive behavior and without corneal clouding
What shuttles fatty acids out of the cytoplasm and into the mitochondria for degradation?
What happens if it is deficient?
Carnitine shuttle
Inability to transport LCFAs into the mitochondria resulting in toxic acumulation
In starvation, glycogen reserves are depleted after __ days
What maintains glucose levels after this?
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
What is the function of each of the following enzymes: Pancreatic lipase: Lipoprotein lipase: Hepatic lipase: Hormone sensitive lipase: LCAT: CETP:
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
Which apolipoprotein activates LCAT?
Which apolipoprotein binds the LDL receptor?
Which is an LPL co-factor?
Which apolipoprotein activates LCAT? - A-1 (HDL)
Which apolipoprotein binds the LDL receptor? - B-100
Which is an LPL co-factor? - C-II
