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MCG Exam 3 > Mitochondrial carriers and substrate shuttles; Pentose phosphate pathway- Lecture 64 > Flashcards

Mitochondrial carriers and substrate shuttles; Pentose phosphate pathway- Lecture 64 Flashcards

1
Q

Name the mitochondrial carriers.

A
  1. phosphate carrier
  2. dicarboxylate carrier
  3. tricarboxylate carrier
  4. alpha-Kg carrier
  5. pyruvate carrier
  6. glutamate carrier
  7. aspartate carrier
  8. adenine nucleotide carrier
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2
Q

What compounds do not have carriers?

A

OAA, alpha GP, DHAP, NADH/NADPH

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3
Q

What does mitochondrial carrier 1 exchange?

A

phosphate for OH

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4
Q

What does mitochondrial carrier 2 exchange?

A

phosphate or malate or succinate for each other

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5
Q

What does mitochondrial carrier 3 exchange?

A

citrate, isocitrate, malate or PEP for each other

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6
Q

What does mitochondrial carrier 4 exchange?

A

alpha- KG for malate

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7
Q

What does mitochondrial carrier 5 exchange?

A

pyruvate for OH or ketone bodies

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8
Q

What does mitochondrial carrier 6 exchange?

A

glutamate for OH

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9
Q

What does mitochondrial carrier 7 exchange?

A

aspartate for glutamate

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10
Q

What does mitochondrial carrier 8 exchange?

A

ADP for ATP

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11
Q

How do mitochondrial carriers 1 and 8 work together?

A

8 transports ATP produced in oxidative phosphorylation out of the mito in exchange for cytosolic ADP (produced from ATP hydrolysis in to the cytosol) while carrier 1 brings ATP plus Pi back to the mito for ATP synthesis

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12
Q

Which carriers can malate be exchanged on?

A

2, 3, and 4

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13
Q

Compounds which cannot enter or leave the mito because they lack carriers have to be _______.

A

transported by substrate shuttle mechanisms.

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14
Q

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

A

reducing equivalents (hydrogen and electrons)

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15
Q

What are shuttles critical for?

A

transporting reducing equivalents from NADH or NADPH into or out of the mito
providing acetyl CoA for fatty acid or cholesterol synthesis
providing carbon intermediates for gluconeogenesis

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16
Q

What are the major shuttles for translocating the reducing equivalents of NADH into the mito?

A

alpha-glycerophosphate (alpha-GP or glycerol 3P)

malate-aspartate (MA) shuttle

17
Q

What is transamination?

A

the transfer of an alpha amino group of one amino acid to a keto acceptor to produce a new amino acid and a new keto acceptor (part of the MA)

18
Q

Describe the alpha glycerophosphate shuttle.

A

DHAP (product of glycolysis) reacts with NADH to produce alphaGP and NAD+ via cytosolic alphaGPDH
need to regenerate DHAP to continue with glycolysis –> alphaGP reacts with outer surface
of mitochondria membrane bound alphaGPDH which also initiates E-FAD –> E-FADH reaction in the membrane (which is regenerated via Q –> QH reaction) which can donate those reducing equivalents to the respiratory chain

19
Q

Describe the MA shuttle.

A

Glycolysis produces NADH which reacts with OAA to regenerate NAD+ and malate (via cytosolic malate dehydrogenase)
malate is transported into the mito viacarriers 2,3, or 4
malate in the mito produces NADH and OAA (via mitochondrial malate dehydrogenase)
OAA must be converted to aspartate to exit the mito via carrier 7 (which is done by converting it from glutamate via aspartate amino transferase with a secondary product of alpha-ketoglutarate)
alphaKG can exit via carrier 4 and, once outside, the reaction can be reversed to produce glutamate (which can reenter the mito via carrier 7) and OAA

20
Q

How can you differentiate between the two mitochondrial shuttle mechanisms?

A

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

21
Q

Describe the flow of the isocitrate shuttle.

A

reducing equivalents of NADPH are used to synthesize isocitrate from alphaKG (via mito NADPH-linked isocitrate dehydrogenase)
isocitrate leaves the mito on carrier 3
isocitrate reacts with cytosolic NADP-linked ICDH to produce NADPH plus CO2 and alphaKG
alphaKG enters mito on carrier 4

22
Q

Where does the PPP pathway occur?

A

the cytosol of liver, adipose, mammary glands, steroidogenic tissues (eg. adrenals), and RBCs
low activity in the brain, muscle, and heart

23
Q

What does the PPP pathway do?

A

uses 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 adn DNA synthesis and for NAD, FAD, CoASH)
reduction of oxidative stress

24
Q

Describe the oxidative steps of the PPP pathway.

A
  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)
25
Q

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

A

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

26
Q

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

A

phosphopentoisomerase
phosphopentoepimerase
transketolase (thiamine pyrophosphate cofactor)
transaldolase

27
Q

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

A

convert pentoses into compounds we can use metabolically

28
Q

What is the net result of the PPP pathway?

A

6 NADP+ +0.5G6P –> 3 CO2 + 6 NADPH

29
Q

What regulates the PPP pathway?

A

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

30
Q

____ is made in aerobic cells from ______. This means that RBCs are ______ because ______.

A

Hydrogen peroxide (H2O2)
mito or autooxidation of ferrous hemes like hemoglobin
always in oxidative stress
H2O2 is a powerful oxidant

31
Q

How do RBCs decompose H2O2?

A 
catalase (heme-containing enzyme that decomposes H2O2 to O2 + H2O)
glutathione peroxide (uses gluthione to catalyze H2O2 + 2 GSH --> 2 H2O + GSSG)
32
Q

How do RBCs regenerate GSH from GSSG?

A

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

33
Q

What is G6PDH deficiency?

A

most common inborn 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

MCG Exam 3 (21 decks)

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