Biochemie P1 Flashcards

1
Q

Where does glycolysis take place?

A

Cytoplasm

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2
Q

Where does oxidation of pyruvate and subsequent ATP synthesis take place?

A

mitochondria

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3
Q

In anaerobic metabolism, why is pyruvate converted to lactate?

A
  1. Pulls the rxn forward (reduces the concentration of pyruvate)
  2. Regenerate NAD+ for more rounds of glycolysis (reoxidize NADH)
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4
Q

What are the most important users of ATP in the body?

A
  1. Ion pumps - Na+/K+ pump, SERCA pump (pumps Ca2+ into ER lumen), PMCA pump (pumps Ca2+ out of the cell)
  2. Contractile/motor proteins which drive muscle contraction
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5
Q

What occurs in the mitochondrial matrix?

A
  • PDH (pyruvate dehydrogenase)
  • CAC enzymes
    Most of the oxidative metabolism occurs within the matrix or within the inner leaflet of the inner mitochondrial membrane.
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6
Q

What occurs in the inner mitochondrial membrane?

A
  • ETC enzymes

- ATP synthase

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7
Q

How many mitochondria in RBCs?

A

none.

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8
Q

Where does heart obtain most of its pyruvate?

a. glycolysis
b. lactate dehydrogenase
c. pentose phosphate pathway
d. catabolism of pye

A

Lactate dehydrogenase - b/c in the heart, the H form of lactate dehydrogenase predominates. This favors conversion of lactate to pyruvate.

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9
Q

How does pyruvate move into the mitochondrial matrix?

A

through membrane transporters. Because remember that glycolysis occurs in the cytoplasm (glucose –> pyruvate), so we need to figure out a way for pyruvate to enter the mitochondrial matrix.

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10
Q

What is the PDH complex composed of?

A

3 distinct enzymes

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11
Q

What are the 5 bound co-factors of PDH complex?

A
  1. TPP
  2. Lipoic acid
  3. CoA
  4. FAD
  5. NAD+
    (TLC FN)
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12
Q

Which co-factor ultimately accepts the carbons of pyruvate?

A

CoA

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13
Q

What does the PDH reaction start with?

A

Pyruvate + CoA + NAD+

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14
Q

What are the products of the PDH reaction?

A

Acetyl CoA + NADH + H+ + CO2

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15
Q

NAD+ is used in ____ rxns generally (catabolic or anabolic)

A

Catabolic reactions, often used in OXIDATIVE reactions

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16
Q

What is the major consequence of aerobic glucose catabolism?

A

production of NADH and FADH2

17
Q

What is the cytosolic ratio of NAD+ to NADH?

A

1000:1 NAD+: NADH
This is because catabolism is an oxidizing process. We need to couple it to a reducing process (NAD+ to NADH) so we have a lot of NAD+. This drives oxidation of the substrate (pyruvate)

18
Q

What is the cytosolic ratio of NADPH: NADP+?

A

100:1 NADPH:NADP+
Because NADPH is used in anabolic reactions (building molecules) - we need to couple it to an oxidation of NADPH so therefore we have more NADPH (reduced form) so we can oxidize it.

19
Q

Lactate dehydrogenase is a mechanism for converting:

a) NADH –> NAD+
b) NAD+ –> NADH

A

NADH –> NAD+

20
Q

What are the 4 B vitamins that PDH requires to do its job?

A
  1. TPP (Vitamin B1/thiamine pyrophosphate): fx: acetyl carrier
  2. CoA (Vitamin B5/pantothenic acid) - fx: acetyl carrier
  3. FAD (Vitamin B2/riboflavin) - fx: electron carrier
  4. NAD+ (Vitamin B3/niacin) - fx: electron carrier
21
Q

What are the steps of the PDH reaction?

A
  1. Pyruvate loses CO2, and the acetyl group remains. Acetyl group passed to TPP.
  2. Acetyl group gets passed from TPP to lipoic acid
  3. Lipoic acid passes the acetyl group to CoA.
  4. At this point, lipoic acid is reduced, and needs to be reoxidized. So, FAD+ –> FADH2 (reduction).
  5. FADH2 needs to be oxidized to FAD. So, NAD+ –> NADH. NADH then goes to ETC –> ATP.
22
Q

What regulates PDH?

A

Indirect allosteric regulation. Directly regulated by phosphorylation.
- Substrates (pyruvate, NAD+) or signs of energy need (ADP) activate PDH. This happens by ADP, NAD+, activating a phosphatase, which activates PDH.

-Products (Acetyl CoA, NADH) or signs of energy abundance (ATP) inhibit PDH. This happens by ATP activating the kinase, which inhibits PDH.

23
Q

What are the 3 steps of ethanol metabolism, and where does it occur?

A

-Ethanol metabolism occurs in the liver.
Steps:
1) Ethanol gets oxidized to acetaldehyde. [occurs in CYTOPLASM]
2) Acetaldehyde gets oxidized to acetate [occurs in MATRIX]
3. Acetate coupled to CoA through thiokinase. Produces Acetyl CoA, which can feed into Citric Acid Cycle. [occurs in MATRIX]

24
Q

PDH is an ______ process.

a) oxidative
b) reductive

A

Oxidative process

25
Q

How many mitochondria do neurons have?

A

Lots, b/c the brain is a metabolically active organ and has a strong preference for glucose. Brain must be able to oxidatively catabolize glucose. Can’t survive on glycolysis alone.

26
Q

What happens (broadly) during CAC?

A
  • Break down of remaining carbons of Ac-CoA to CO2
  • Generate lots of reducing equivalents (NADH, FADH2)
  • Very little ATP (actual energy) generated by CAC
27
Q

Where does CAC take place?

A

Mitochondrial matrix

28
Q

Steps of CAC

A

1) Acetyl-CoA (2C) gets combined with Oxaloacetate (4C) to make citrate.
2) In 2 successive steps, 2 CO2 molecules are released.

29
Q

What “energy” is created in the CAC?

A

1 GTP is generated.

30
Q

What else does the CAC generate?

A

3 NADH
1 FADH2
(these are reducing equivalents which will be used in the ETC)

31
Q

What is the major regulatory step of the CAC? What inhibits/activates it?

A

IDH (isocitrate dehydrogenase)
- An irreversible step

Inhibited by: ATP, lower NAD+:NADH ratio
Activated by: ADP, higher NAD+:NADH ratio

32
Q

What is the significance of IDH inhibition?

A

Means that citrate can be used for fatty acid synthesis in times of high ATP.
- Citrate is the initial ingredient in fatty acid synthesis.

33
Q

CAC intermediates are used for many other things:

A

1) Oxaloacetate –> amino acids, purines, pyrimidines
2) Citrate –> fatty acids, sterols
3) Ketoglurate –> amino acids, purines
4) Succinyl CoA –> porphyrins

34
Q

What are the mechanisms to replace CAC intermediates?

A

The mechanisms are called anaplerotic reactions:

1) Pyruvate carboxylase: used to replenish oxaloacetate
2) Glutamine deamination: makes alpha-ketoglutarate

35
Q

To generate ATP from all non-glucose fuel sources (fatty acids, ketone bodies, amino acids), this requires:

A

oxygen!

36
Q

CAC releases: ____ CO2 molecules and generates ___ NADH and ____ per glucose

A

2 CO2 molecules
6 NADH
2 FADH2

37
Q

What allosterically stimulates IDH? What inhibits it?

A

Stimulated by ADP

Inhibited by ATP

38
Q

How many mitochondria does the heart have?

A

Lots