Biochem part deux

Question 1

What are the three non-reversible, controlled steps, of glycolysis?

Answer 1

Hexokinase (Glucokinase)
PFK1
Pyruvate kinase

Question 2

What tissues have glucokinase instead of hexokinase? What are the major differences between the two enzymes?

Answer 2

Glucokinase is in the liver and pancreatic beta-cells

Glucokinase is induced by insulin and has a higher Km and a higher Vmax

Question 3

What activates PFK1 activity?

Answer 3

Low energy conditions…AMP and fructose-2,6-BP

Question 4

What inactivates PFK1 activity?

Answer 4

High energy conditions…ATP and citrate (citrate is the first product of the TCA cycle)

Question 5

Knowing that glucagon’s role is to increase increase plasma glucose (kinda), would FBP2 (fructose bisphosphatase 2) or PFK2 be activated in a low insulin:glucagon ratio?

Answer 5

Glucagon binding its receptor will increase cAMP and activate PKA…which phosphorylates the FBP2/PFK2 complex. This activates FBP2.

This makes sense…FBP2 dephosphorylates fructose-2,6-BP to fructose-6-P…taking away an activator of PFK1

Question 6

What is the rate limiting step of gluconeogenesis?

Answer 6

Fructose-1,6-bisphosphatase

Question 7

In what cells does gluconeogenesis occur?

Answer 7

Hepatocytes
Kidney
Intestinal epithelium

Question 8

Glycogen phosphorylase is the first step of glycogenolysis. What symptoms would be expected in a person deficient of this enzyme?

Answer 8

McArdle disease presents with increased glycogen in muscle → swelling and lysing (Rhabdomyolysis) → myoglobinuria and renal failure

Normal life expectancy

Question 9

a-1,6-glucosidase is the deb ranching enzyme. What would be the expected symptoms in a patient deficient of this enzyme?

Answer 9

Cori’s disease presents with mild hypoglycemia…no elevation in lactate levels or uric acid

Question 10

A mother brings in her 1yr old because of seizures and a protuberant abdomen. A fasting glucose test is performed and found to be incredibly low. What disease does this chid have? What are other expected findings? What is treatment regimen?

Answer 10

This child has Von Gierke disease…a deficiency in glucose-6-phosphatase

Big kidneys and hepatomegaly are causing the big belly. And there would likely be increased serum lactate, increased uric acid, and hypertriglyceridemia

Von Gierke disease can be treated by eating frequently and by eating corn starch before bed (breaks down slow)

Question 11

Pompe disease is a deficiency of a-1,4-glucosidase in lysosomes. How does this disease present in children? Adults?

Answer 11

No a-1,4-glucosidase activity causes infantile Pompe disease → severe muscle weakness, cardiomegaly, and cardiac failure → life expectance is less than 1yo

Decreased a-1,4-glucosidase activity causes adult Pompe disease → gradual onset of muscle weakness (diaphragm weakness → respiratory failure)…NO cardiac involvement

Question 12

A mother brings in her 3yo because he doesn’t like to walk and run around like he used to and his calves seem to have swollen. She says that she has an uncle who had a similar condition. What is causing this boys symptoms?

Answer 12

Duchenne muscular dystrophy is caused by a frameshift mutation that leads to truncated dystrophin protein and accelerated muscle breakdown

Question 13

What are some fundamental differences between Duchenne muscular dystrophy and Becker muscular dystrophy?

Answer 13

AGE…Duchenne <5yo while Becker is in adolescence/early adulthood

Also, Becker is usually caused by a point mutation (compared to the frameshift mutation seen in DMD)…but both are X-linked

Question 14

What can inhibit complex I of the ETC?

Answer 14

Amytal
Rotenone
MPP (same MPP that can cause Parkinsonian symptoms)

Question 15

What can inhibit complex III of the ETC?

Answer 15

Antimycin A

Question 16

What can inhibit complex IV of the ETC?

Answer 16

Cyanide
CO
H2S
NaN3 (azide)

Question 17

What can inhibit complex V (ATPase) of the ETC?

Answer 17

Oligomycin A

Question 18

What can uncouple the ETC?

Answer 18

Thermogenin (hibernation)
Aspirin
2,4-DNP

Question 19

It is well known that fava beans can precipitate G6PD to act up, but clinically this isn’t that important. Which drugs do this…because that’s what could be on the test?

Answer 19

Sulfonamides (TMP-SMX)
Primaquine (anti-malarial)
Anti-TB drugs

Question 20

Tall patient with intellectual disability comes to the clinic with a subluxed lens. Which direction did the eye sublux? What is likely elevated in this patient’s urine?

Answer 20

Homocystinuria causes the lens to sublux down and in

Marfan’s subluxed eye usually goes up and out

Question 21

Essential fructosuria is benign. What is the deficient enzyme in essential fructosuria?

Answer 21

Fructokinase is deficient in essential fructosuria

Question 22

Fructose intolerance causes hypoglycemia, jaundice, cirrhosis, and vomiting. What is the deficient enzyme in fructose intolerance?

Answer 22

Aldolase B is deficient in fructose intolerance

Question 23

Galactokinase deficiency causes infantile cataracts d/t the accumulation of galactitol. What is the deficient enzyme in galactokinase deficiency? What enzyme is overactive in galactose deficiency?

Answer 23

As the name implies…galactokinase is deficient in galactokinase deficiency

Aldose reductase is OVERACTIVE in galactokinase deficiency (same enzyme coverts glucose to sorbitol)

Question 24

Classic galactosemia causes FTT, jaundice, hepatomegaly, infantile cataracts, and intellectual disability. What is the deficient enzyme in classic galactosemia?

Answer 24

Galactose-1-P uridyltransferase is deficient in classic galactosemia