Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Block 2 - Week 1 > One-Carbon Metabolism > Flashcards

One-Carbon Metabolism Flashcards

1
Q

What cycles/pathways does one-carbon metabolsim include?

A
  • Folate cycle
  • Methionine cycle
  • Transsulfuration pathway
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are 3 reactions THF (tetrahydrofolate) is needed for?

A
  • Synthesis of dTMP (which is essential for DNA synthesis)
  • Synthesis of purine nucleotides
  • Vitamin B12-dependent re-methylation of homocysteine to form methionine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q
  • What are sources of natural folates?
  • What are sources of synthetic folic acids?
A

Natural folates:

  • Nuts
  • Chickpeas
  • Leafy greens

Synthetic folic acids:

  • Added to many grain products to prevent NTDs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

THF is the ____ ____ form of folate and accepts one-carbon groups at positions ____, ____, or both, and transfers these groups to other compounds

A

THF is the active coenzyme form of folate and accepts one-carbon groups at positions N5, N10, or both, and transfers these groups to other compounds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Synthetic folic acids have a fully-oxidized pteridine ring and ____ glutamate residue

A

Synthetic folic acids have a fully-oxidized pteridine ring and single glutamate residue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Natural folates and those in humans contain a ____ ____ that aids in their cellular retention

A

Natural folates and those in humans contain a polyglutamate tail that aids in their cellular retention

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

The polyglutamate tail of natural folates must be removed by a ____ ____-____ ____ prior to intestinal absorption

A

The polyglutamate tail of natural folates must be removed by a jejunal brush-boarder peptidase prior to intestinal absorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q
  • What is the transporter involved in folate absorption?
  • What does a defeciency in this lead to?
A
  • Proton-coupled folate transporter (PCFT)
  • Failure to thrive and megablastic anemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q
  • What is the transporter involved in folate transport into the interstitial space?
  • Where is this transporter expressed?
A
  • Reduced folate carrier (RFC)
  • Ubiquitously expressed in cells/tissues (is the major folate transporter)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are 3 conditions that affect folate absoption?

A
  • Excessive alcohol intake
  • Crohn’s disease
  • Celiac disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What converts folate to dihydroflate (DHF) to tetrahydrofolate (THF)?

A

DHFR (dihydrofolate reductase)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q
  • What converts DHF to THF in the folate cycle?
  • What is required for this process?
A
  • DHFR (dihydrofolate reductase)
  • NADPH which gets converted to NADP+
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

THF reacts with ____ to form ____ which is essential in purine synthesis

The enzyme for this reaction is ____

A

THF reacts with formate to form N10-formyl-THF which is essential in purine synthesis

The enzyme for this reaction is formyl-THF synthase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are 2 sources of formate?

A
  • Catabolism of tryptophan
  • Metabolism of methanol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

____ is important in purine synthesis

____ is a required substrate in this process

A

N10-formyl-THF is important in purine synthesis

AICAR (S-aminoimidazole-4-carboxamide ribonucleotide) is a required substrate in this process

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

____ in urine is a diagnositc sign of folate deficiency if it occurs after a test dose of ingested histidine

A

FiGlu in urine is a diagnositc sign of folate deficiency if it occurs after a test dose of ingested histidine

(this is because low THF leads to the accumulation of FIGlu after histidine catabolism)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

N10-formyl-THF can be reduced to form ____

Catabolism of ____ also produces this

A

N10-formyl-THF can be reduced to form N5,N10-methenyl-THF

Catabolism of histidine also produces N5,N10-methenyl-THF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

N5,N10-methenyl-THF can be reduced to form ____

This reaction requires ____

A

N5,N10-methenyl-THF can be reduced to form N5,N10-methylene-THF

This reaction requires NADPH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Glycine can be reversibly converted Serine

In this reaction ____ is reversibly converted to ____

This requires vitamin ____ and enyzme ____

A

Glycine can be reversibly converted Serine

In this reaction N5,N10-methylene-THF is reversibly converted to THF

This requires vitamin B6 and enyzme SHMT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

dTMP is essential for ____

This is created in the folate cycle by the conversion of ____ to ____

A

dTMP is essential for DNA synthesis

This is created in the folate cycle by the conversion of N5,N10-methylene-THF to DHF

Note: this is why THF is absolutely required for DNA synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How does a folate deficiency impair cell division in rapidly growing cells?

A
  • decreased dTMP from dUMP –> decrease DNA synthesis
  • decreased purine synthesis
  • decreased repair of damaged DNA
  • increased dUMP –> dU incorporated into DNA –> increased DNA fragmentation
22
Q

Causes of megaloblastic anemia

A

Folate and/or vitamin B12 deficiency

23
Q

Megaloblastic anemia

A
  • Condition in which the bone marrow produces unusually large structurally abnormal, immature RBCs (megaloblasts)
  • Results from defective DNA synthesis and unbalanced cell growth from B12 and/or folate deficiency
  • Immature RBCs have increasedd MCV > 100 fl
    • Spleen normally removes megaloblasts when they reach peripheral circulation
24
Q

Folate deficiency causes ____ neutrophils

A

Folate deficiency causes hypersegmented neutrophils

25
Q

Glossitis

A
  • Condition where the tongue is swollen/inflamed/glossy
  • Results from defective replacement of damaged papila
  • Can be caused by:
    • Folate or iron deficiency
    • Allergies
    • Infections
26
Q

Methotrexate is a ____ of ____

High doses of methotrexate inhibit rapid cell growth in certain cancers. Name 4 examples.

A

Methotrexate is a competitive inhibitor of DHFR

High doses of methotrexate inhibit rapid cell growth and can be used to treat certain cancers such as:

  • Acute lympoblastic leukemia
  • Breast Cancer
  • Osteosarcoma
  • Advanced Non-Hodgkin’s Lymphoma
27
Q

Leucovorin Rescue

A

N5-Formyl-THF (AKA leucovorin) is a natural storage form of folate used as an antidote to the harmful effects of methotrexate on healthy cells by bypassing the need for activation by DHFR

28
Q

Vitamin B12 connects ____ cycle to the ____ cycle

Within this connection N5-methyl-THF is converted to THF in the folate cycle, and ___ is converted to ____ in the methionine cycle

Note: This step is B12 dependent

A

Vitamin B12 connects folate cycle to the methionine cycle

Within this connection N5-methyl-THF is converted to THF in the folate cycle, and homocysteine is converted to methionine in the methionine cycle

Note: This step is B12 dependent

29
Q

Lower doses of methotrexate are used to reduce ____ and treat symptoms of ____

Methotrexate promotes the intracellular accumulation of purine biosynthetic intermediate ____ which leads to the production of ____ which has potent anti-inflammatory effects

A

Lower doses of methotrexate are used to reduce inflammation and treat symptoms of rheumatoid arthritis

Methotrexate promotes the intracellular accumulation of purine biosynthetic intermediate AICAR which leads to the production of adenosine which has potent anti-inflammatory effects

30
Q

The methionine cycle produces ____ which acts as a methyl group donor

4 examples of methlation reactions are:

A

The methionine cycle produces SAM (S-adenosylmethionine) which acts as a methyl group donor

4 examples of SAM methlation reactions are:

  • Hormone synthesis: Norepinpehrine –> Epinephrine
  • Phospholipid synthesis: PE –> PC
  • DNA methylation
  • Histone methylation
31
Q

After SAM donates a methyl group it becomes ____ which is then converted into ____

A

After SAM donates a methyl group it becomes SAH (S-adenosylhomocysteine) which is then converted into homocysteine

32
Q

Homocysteine can be remethylated to ____ in the ____

This reaction requires ____ which comes from ____

A

Homocysteine can be remethylated to methionine in the liver

This reaction requires betaine which comes from choline

33
Q

Homocysteine can be condensed with ____ to form ____ via the enzyme ____

____ can then be converted into cysteine and a-ketobutyrate. Cysteine inhibits ____. This feedback inhibition keeps methionine from being used for cysteine synthesis unless needed.

These reactions all require vitamin ____

A

Homocysteine can be condensed with serine to form cystathionine via the enzyme cystathionine B-synthase

cystathioine can then be converted into cysteine and a-ketobutyrate. Cysteine inhibits cystathionine B-synthase. This feedback inhibition keeps methionine from being used for cysteine synthesis unless needed.

These reactions all require vitamin B6

34
Q

____, the oxidized disulfide of homocysteine, is not efficiently reabsorbed by the kidneys, causing ____ when homocysteine metabolism is impaired

A

Homocystine, the oxidized disulfide of homocysteine, is not efficiently reabsorbed by the kidneys, causing homocystinuria when homocysteine metabolism is impaired

35
Q

Causes of homocystineuria (4 examples)

Treatment of most common cause (3 examples)

A
  • Vitamin B12 or folate deficiency
  • Methionine synthase deficiency
  • Severe vitamin B6 (pyridoxine) deficiency
  • Most commone cause: cystathionine B-synthase (CBS) deficiency) –> termed classic homocystinuria

Treatment of CBS deficiency:

  • Vitamin B6 (pyridoxine) supplements to increase resdiual enzyme activity in patients with B6 responsive variants
  • Reduce dietary methionine + give supplemental cysteine
  • Supplementation with betaine to increase utilization of hepatic pathway for homocysteine metabolism
36
Q

Clinical characteristics of classic homocystinuria

A
37
Q

Mutations in ____ can result in cystathioninuria which is pathologically benign and can be treated with ____ supplements

A

Mutations in cystathionase can result in cystathioninuria which is pathologically benign and can be treated with B6 supplements

38
Q

Folate deficiency in early pregnancy results in ____

A

Folate deficiency in early pregnancy results in neural tube closure defects

39
Q

Increased risk of NTDs was first observed in women with a temperature sensitive varient of ____

In these women there was a decrease of ____ and an increase of ____

A

Increased risk of NTDs was first observed in women with a temperature sensitive varient of methyl-THF reductase

In these women there was a decrease of N5-methyl-THF and an increase of homocysteine

40
Q

It is recommended to pregnant women to consider taking ____ supplements to decrease the risk of ____

A

It is recommended to pregnant women to consider taking folic acid supplements to decrease the risk of NTDs

41
Q

Neural tube closure occurs ~____ days post-conception

A

Neural tube closure occurs ~23 days post-conception

42
Q

The most common severe congenital NTDs associated with folate deficiency in early pregnancy are ____ and ____

A

The most common severe congenital NTDs associated with folate deficiency in early pregnancy are spina bifida and anencephaly

43
Q

In addition to decreased DNA synthesis, folate deficiency may also alter what?

A
  • Decreased levels of neurotransmitters
  • Decreased hypomethylation of DNA which leads to increased expression of certain micro RNAs
44
Q

What are the irreversible reactions in the folate cycle?

(have a general idea)

A

Irreversible reactions are shown by the red arrows in the picture

Have a general idea of what they are

45
Q

Vitamin B12 is only produced by ____

Major dietary sources of B12 include (3 examples)

____ and ____ are at risk for B12 deficiency

A

Vitamin B12 is only produced by bacteria

Major dietary sources of B12 include:

  • Meat
  • Eggs
  • Dairy products

Vegetarians/vegans and some elderly patients are at risk for B12 deficiency

46
Q

Enough B12 is stored in the ____ to last ____ years

A

Enough B12 is stored in the liver to last 3-5 years years

47
Q

Vitamin B12 and the methyl trap hypothesis

A
  • The methlene-THF reductase reaction is irreversible
  • A vitamin B12 deficiency creates a functional (or secondary) folate deficiency by trapping folate as N5-methyl-THF
    • Results in megaloblastic anemia
48
Q

Intestinal absorption of vitamin B12

A
  1. Pepsin digests any bound dietary protein (vitamin B12 can be free or protein bound)
  2. R-binders (transcobalamin I) bind free B12
  3. R-binders are destroyed by pancreatic proteases
  4. Intrinsic factor-B12 complex attaches to specific receptors (without intrinsic factor B12 is exreted in stool)
  5. Complex is internalized, carried in blood by transcobalamin II to liver and other tissues
49
Q

Vitamin B12 deficiency may also cause ____

5 examples

A

Vitamin B12 deficiency may also cause irreversible neurological symptoms, including:

  • Symmetric numbness/tingling of feet
  • Diminishing vibratory and position sense
  • Progression to a spastic gait disturbance
  • Auditory and visual hallucinations (megaloblastic madness)
50
Q

Severe vitamin B12 deficiency results in the accumultion of ____ causing ____

A

Severe vitamin B12 deficiency results in the accumultion of L-methylmalonyl CoA causing methylmalonic acidemia

Note: If L-methylmalonyl CoA is used in place of Malonyl-CoA in FA synthesis –> results in formation of methyl branched FAs which when incorporated into myelin sheath –> causes destablization and neuron loss –> results in neurological symptoms

51
Q

Why is it important to assess vitamin B12 levels in patients with megaloblastic anemia and not simply treat with suupplemntal folate?

A

Because if the megaloblastic anemia is due to a vitamin B12 deficiency, this could lead to permanent neurological symptoms!

52
Q

Potential dangers of excess folate

A
  • Could hide a vitamin B12 deficiency by correcting the anemia caused by the B12 deficiency but won’t prevent the permanent neurological damage
  • High doses of folic acid may accelerate the progression of preneoplastic lesions, increasing the risk of colorectal and possibly other cancers in specific individuals

Block 2 - Week 1 (9 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions