Biochem 2

Question 1

Pyruvate kinase deficiency in RBCs.

Pathogenesis?

Answer 1

Pyruvate kinase is needed in glycolysis and production of ATP. RBCs need this ATP to maintain cell structure.
Deficiency: hemolysis and damaged RBCs are removed by splenic red pulp macrophages – hemolytic anemia, splenomegaly (hyperplasia).

Question 2

Reperfusion injury

Answer 2

Arterial blood flow is restored to ischemic tissue –> O2 reacts to xanthine oxidase, NADPH oxidase, NO synthase –> ROS prodn.
Post-ischemia (Acute compartment syndrome): ROS prodn > antioxidant neutralizing capacity – inc. cell injury and death.

Question 3

Glycogenolysis in liver vs. skeletal muscle

Answer 3

> Liver: maintain blood glucose levels; glucagon and epi can induce glycogen phosphorylase via adenylate cyclase.
Skeletal muscle: energy for muscle contraction; Epi induces glycogen phosphorylase via adenylate cyclase; Epi and ACh can inc. intracellular Ca (from SR) and cause glycogen breakdown during contraction (Ca-induced phosphorylase kinase also activates phosphorylase).
*NO GLUCAGON RECEPTORS in skeletal muscle

Question 4

Riboflavin (B2) deficiency

Answer 4

B2 needed for enzymes in ETC and TCA cycle to generate FMN and FAD – coenzymes in redox rxns.
Seen in chronic alcoholics, malnourished.
>Deficiency: angular stomatitis, cheilitis, glossitis, eye changes, seborrheic dermatitis, anemia

Question 5

Base excision repair process (enzyme order)

Answer 5

For single-base DNA defects.

>Glycosylase – endonuclease, lyase – polymerase – ligase

Question 6

Pigment stones

[Causes]

Answer 6

> Chronic hemolytic anemia: excess CB excreted in bile and deconjugated by beta-glucuronidase in biliary tract.
Bacterial (E.coli), helminthic (Ascaris, C. sinensis): injured hepatocytes release beta-glucuronidase – hydrolyzes bilirubin glucuronides – inc. UCB

Question 7

In what conditions is ATP sometimes not generated in glycolytic pathway of RBCs?

Answer 7

In normal glycolysis, Phosphoglycerate Kinase step generates ATP when converting 1,3-BPG to 3-phosphoglycerate.
In hypoxia or chronic anemia: 1,3-BPG –> Mutase –> 2,3-BPG –> Phosphatase –> 3-phosphoglycerate.
No ATP yielded – sacrificed to inc. 2,3-BPG – dec. O2 affinity – inc. O2 delivery to tissues.

Question 8

Amatoxins.

From what? Inhibit what? Sx?

Answer 8

Poisonous mushrooms (Death caps, Amanita phalloides).
Inhibit RNA polymerase II -- dec. mRNA synth -- apoptosis.
Affects GIT and PCT: abdominal pain, vomiting, cholera-like diarrhea; acute hepatic and renal failure.

Question 9

Heme-heme interactions of Hemoglobin?

Why do separated Hgb units act similarly to myoglobin? Dissociation curve?

Answer 9

> After binding to one O2, the O2 affinity of the other heme moieties increases – SIGMOID shape on Hgb-O2 dissociation curve.
Myoglobin is monomeric, so no heme-heme interactions – inc. O2 affinity – HYPERBOLIC curve.
Separated Hgb subunits are monomeric like myoglobin – similar O2-binding behavior – HYPERBOLIC