AC Lecture 64: Carriers, Shuttles, Pentose Pathway

Question 1

Name the mitochondrial carriers.

Answer 1

1. phosphate (phosphate and OH)
2. dicarboxylate (malate and succinate)
3. tricarboxylate (citrate, isocitrate, malate, or PEP)
4. alpha-Kg (alpha-KG and malate)
5. pyruvate (pyruvate, OH, ketone bodies)
6. glutamate (glutamate and OH)
7. aspartate (aspartate and glutamate)
8. adenine nucleotide (ATP/ADP)

Question 2

What compounds do not have carriers?

Answer 2

OAA
alpha GP
DHAP
NADH/NADPH

Question 3

What carriers can malate be exchanged on?

Answer 3

2, 3, and 4

Question 4

How are compounds that don’t have shuttles transported into the mito?

Answer 4

substrate shuttle mechanisms

Question 5

Since NADH/NAD+ and NADPH cannot enter or leave the mito, what must be transported instead?

Answer 5

reducing equivalents (hydrogen and electrons)

Question 6

How can you differentiate between the two mitochondrial shuttle mechanisms?

Answer 6

alphaGP makes FADH
MA makes NADH
alphaGP does not cross the mito membrane (could inhibit carriers and only affect MA)
different enzymes are used for each

Question 7

Where does the PPP pathway occur?

Answer 7

the cytosol of the liver, adipoase, mammary glands, steroidogenic tissues (e.g. adrenals), and RBCs
low activity in the brain, muscles, and heart

Question 8

What does the PPP do?

Answer 8

use glucose to:
produce NADPH (needed for synthesis of cholesterol, fatty acids, steroids, detoxification reactions by the cytochrome P450 system)
production of ribose (needed to produce the nucleotides for RNA/DNA synthesis and for NAD, FAD, CoASH)
reduction of oxidative stress

Question 9

Describe the oxidative steps of the PPP pathway.

Answer 9

1. glucose-6P + NADP+ –> 6 phosphogluconic acid + NADPH (via G6P dehydrogenase)
2. 6-phosphogluconic acid + NADP+ –> CO2 + ribulose 5-P + NADPH (via 6-phosphogluconic acid dehydrogenase)

Question 10

List the important intermediates of the non-oxidative steps of the PPP pathway.

Answer 10

Ribulose 5P
Xyulose-5P
sedoheptulose-7P
erythrose-4P

Question 11

List the important enzymes involved in the non-oxidative steps of the PPP pathway.

Answer 11

phosphopentoisomerase
phosphopentoepimerase
transketolase (thiamine pyrophosphate cofactor)
transaldolase

Question 12

What is the function of the non-oxidative PPP pathway?

Answer 12

convert pentose into compounds we can use metabolically

Question 13

What regulates the PPP pathway?

Answer 13

availability of G6P and need for NADPH (NADPH/NADP ratio)

Question 14

Why are RBCs always in oxidative stress?

Answer 14

hydrogen peroxide is made in aerobic cells from the autooxidation of ferrous hemes like hemoglobin

Question 15

How do RBCs decompose H2O2?

Answer 15

catalase (heme-containing enzyme that decomposes H2O2 to O2 + H2O)
gluthione peroxidase (uses gluthione to catalyze H2O2 + 2 GSH --> 2 H2O + GSSG)

Question 16

How is GSH regenerated?

Answer 16

GSSG + 2 NADPH –> 2 GSH + 2 NADP+ (via gluthione reductase)

Question 17

What is G6PDH deficiency?

Answer 17

most common error of metabolism
severity determined by how much G6PDH activity is present
complete deficiency is embryonically lethal)
individuals are sensitive to oxidative stress (via drugs, foods, chemicals, high O2, high altitude) resulting in hemolytic anemia due to inability to efficiently clear H2O2 from RBCs