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Nutr 3330 > Midterm (Lec 5) > Flashcards

Midterm (Lec 5) Flashcards

1
Q

Folate

A

Initially discovered as a growth factor in green leafy vegetables ”foliage”

Folate forms in foods and body
Supplemental form in fortified foods and supplements is folic acid

Chemical name is pteroylglutamate/pteroylglutamic acid

Number of glutamates varies from 5-8 ; need it at 1 to absorb LOOK AT STRUCTURE

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2
Q

Folate absorption

A

Majority of food folates are polyglutamates

Must be cleaved to mono glutamate for absorption

Allows folate to be absorption

Many drugs compete with folate
- inhibit absorption
- compete for transport

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3
Q

Folate transport

A

Folate binding proteins (usually don’t need binding proteins for B vitamins)

Identified in plasma and other tissues

Bind folate with high affinity

Transports folate to liver and other cells

Cells store folate by adding back glutamates (can’t be stored without glutamate)

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4
Q

Folate Coenzyme

A

Needs to be converted to its coenzyme form o perform metabolic roles TETRAHYDROFOLATE

Activated by reduction (adding hydrogens) - added to positions 5,6,7,8

Folate -> dihydrofolate -> tetrahydrofolate (THF)

Dihydrofolate reductase is the enzyme

Niacin adds H to folate

THF
- fully reduced state
- must be in this form to carry carbon units and perform metabolic role
— ONE CARBON UNITS added to THF

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5
Q

Folate metabolic role: single carbon metabolism

A

Calling card of folate (THF)

Acceptor and donor of 1-carbon units

Important in:
- amino acid metabolism
- nucleotide metabolism

Ex: methyl group CH3
- transfer of methyl groups involved in many reactions
- folate central in methyl group transfer

-recall other carbon groups that are transferred by THF

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6
Q

Folate: amino acid metabolism

A

Methionine Synthesis
- involved homocysteine (hcy to met)
- Folate deficiency will build up homocysteine
- also needs B12

Histidine catabolism
- basis for a folate deficiency test: FIGLU LOAD TEST

interconversion of serine and glycine
- serine OH methyltransferase
- needs B6

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7
Q

Nucleotide metabolism

A

Synthesis of purines and pyrimidines
- heterocyclic nitrogenous compounds
- purine (adenine, guanine) and pyrimidine bases (uracil, thymine, cytosine)

Allow synthesis of nucleosides and nucleotides
- ex: ATP - a nucleotide synthesized from purine

DNA synthesis
- needed for DNA synthesis (key focus for folate)
- crucial for cell division and growth
- ex: folate acts as a coenzyme for enzyme involved in DNA synthesis:
——— thymidylate synthetase (key enzyme)

All involve transfer of one carbon units

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8
Q

Methotrexate

A

Chemotherapy drug
Inhibits DHFR - dihydrofolate reductase
- decreases THF therefore less DNA synthesis and less cancer cell replication

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9
Q

Folate food products

A

Dark green vegetables

Fortified products
- folic acid in white flour, pastas, corn meal

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10
Q

Folate deficiency

A

due to diet, drugs, or malabsorption

Same anemia as B12 deficiency
Weakness, depression
Increased homocysteine

NEURAL TUBE DEFECTS - birth defect

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11
Q

Folate can mask B12 deficiency

A

You will have macrocytic anemia with either b12 or folate deficiency

Supplements of either will correct the anemia BUT not other symptoms

Aka if you have inadequate B12 with adequate folate your will NOT see anemia
- fortified foods could be causing B12 deficiency by masking symptoms

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12
Q

Diagnosing folate deficiency with FIGLU

A

Also called histidine load test

Method to diagnose folate deficiency

  • give excess histidine
  • 24 hour urine collection/blood sample
  • measure FIGLU in urine OR blood
  • if high = folate deficiency
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13
Q

Dietary folate equivalents

A

Folate: in food
Folic acid: in fortified foods and supplements

Bioavailability ranking
1. Supplemental folic acid on an empty stomach
2. Fortified foods
3. Foodfolate (lowest since it’s bound to other food components)

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14
Q

Folate and NTDS

A

Folic acid supplementation reduces risk of neural tube defects

Event occurs when tube is closing (21-28 days post conception)

Women should always be supplementing with folate but our flour is fortified (could contribute to masked B12 deficiency?)

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15
Q

Folate can decrease cancer risk

A

Folate plays a key role in proper DNA and RNA synthesis as well as genetic stability

Folate intake related to decreased cancer risk (colorectal most evident)

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16
Q

Folate can increase cancer risk

A

Folate can also facilitate multiplication of cancer and pre cancerous cells (high proliferation rate)

Cancer cells need folate to maintain thymidine synthesis at a pace needed to maintain high DNA synthesis

CORE ISSUES:
- timing of exposure (better in beginning of life vs later bc you could have pre cancerous cells already)
- level of exposure (too much or too little)
- form of exposure (folate vs folic acid)

17
Q

Homocysteine

A

Intermediate of methionine metabolism

Not present in the diet + not incorporated into protein

Associated with CVD

Possible role in dementia and Alzheimer’s

18
Q

Homocysteine fates

A

3 fates
- remethylation to methionine (needsfolate, B12, choline)
- transulfuration to cysteine (needs B6)
- release into circulation

Example of inter relationships among nutrients to optimize human health

19
Q

Choline

A

Nutritional importance discovered when animals fed choline free diet developed fatty liver disease which resolved when fed choline

TPN without choline induces symptoms: fatty liver and liver damage, resolved when choline added

20
Q

Choline structure

A

Simple structure

Serves as methyl group donor - can be synthesized from methionine

Choline then synthesized to:
- phosphatidylcholine
- acetylcholine
- betaine

RECOGNIZE STRUCTURE

21
Q

Choline metabolic role

A

Precursor for phosphatydilcholine
- phospholipid
- essential part of all cell membranes
- membrane structure and fluidity
- lipid transport (lipoproteins) : packages them up (we would have lipid build up and fatty liver without this)
- CHOLINE OCCURS AS PHOSPHATYDILCHOLINE / LECITHIN IN FOOD

Precursor for acetylcholine
- neurotransmitter
- muscle control, memory

Precursor for betaine
- transmethylation reactions
- single carbon metabolism
- needed to convert homocysteine to methionine (+ b12 and folate)

22
Q

Choline deficiency

A

Can be synthesized in our body and widely present in foods

Deficiency signs:
- elevated liver enzymes (sign of liver dysfunction)
- fatty liver

23
Q

Choline and cognitive function

A

Correlated since choline is a precursor for acetylcholine

Early life choline can diminish severity of memory deficits in later life
- role for Alzheimer’s? (Patients have a low conversion of choline to acetylcholine in the brain) only moderate improvements have been seen with lecithin

24
Q

Choline and cancer

A

Choline deficiency associated with increased liver cancer and increased sensitivity to liver carcinogens in rats (no human data)

Relation to fatty liver damage from choline deficiency

25
Q

Choline and CVD prevention

A

Choline as a precursor to betaine

Involved in reducing homocysteine in the blood

Works with folate and B12

26
Q

Too much choline

A

TMAO: Trimethylamine N-oxide

TMAO is a metabolite of choline that is produced from intestinal bacteria

TMAO has been associated with INCREASED risk of heat disease

TMAO is Ana drive area of research in relation to other areas of health as well

Nutr 3330 (21 decks)

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