test 2 study guide

Folate: deficiency markers

Folate deficiency can cause

high FIGLU

high homocysteine

low serum folate

low RBC folate

Vitamin B12: deficiency markers

B12 deficiency can cause

high homocysteine

high methylmalonic acid/methylmalonyl-CoA. High MMA is specific for B12 deficiency

Vitamin B6: deficiency markers

B6 deficiency can cause

low plasma PLP

high homocysteine.

PLP is the main active form of B6

Vitamin E: deficiency markers

Vitamin E deficiency can cause

abnormal RBC hemolysis

Vitamin K: deficiency markers

Vitamin K deficiency can cause

prolonged clotting time

bleeding

high prothrombin time

Folate: role in methionine cycle

Folate as 5-methyl THF gives a methyl group to B12, which helps convert homocysteine to methionine. This supports SAM production.

Vitamin B12: role in methionine cycle

B12 accepts a methyl group from 5-methyl THF and gives it to homocysteine, converting homocysteine into methionine.

SAM: importance

SAM is a major methyl donor used for DNA, RNA, protein, lipid, histone, gene expression, and myelin-related methylation reactions.

Methyl folate trap

The methyl folate trap happens in B12 deficiency. Without B12, 5-methyl THF cannot give away its methyl group, so folate gets trapped and cannot return to THF forms needed for DNA synthesis.

FPG / folylpolyglutamate synthetase

FPG adds glutamate residues to folate inside cells. This traps folate inside the cell as polyglutamate folate.

MTHFR / methylene THF reductase

MTHFR converts 5,10-methylene THF into 5-methyl THF, which is needed for the methionine cycle.

DHFR / dihydrofolate reductase

DHFR converts DHF into THF, the active folate form. It is needed to activate folate.

LRAT

LRAT is a vitamin A enzyme that converts retinol into retinyl esters for storage or transport.

Transducin

Transducin is a vision G-protein activated by rhodopsin after light hits the retina. It helps start the visual signal pathway.

Parathyroid hormone / PTH

PTH raises blood calcium by acting on bone and kidney and helping activate vitamin D. It is not an enzyme.

Folate: absorption requirements

Food folate is usually polyglutamate and must be converted to monoglutamate before absorption. This requires folate hydrolase/glutamate carboxypeptidase, a zinc-dependent enzyme.

Folate: what decreases absorption/status

Folate absorption/status can decrease with zinc deficiency, alcohol, malabsorption, certain drugs, cooking, heat, oxidation, UV light, and B12 deficiency.

Folate: PCFT transporter

PCFT is the main intestinal folate transporter. It moves folate from the GI lumen into the enterocyte and works best in acidic pH.

Folate: MRP3/MRP5 transporters

MRP3 and MRP5 move folate out of the enterocyte and into the blood.

Folate: RFC transporter

RFC moves folate from the blood into body cells. It works best in neutral pH.

Folate: folate receptors

Folate receptors bring folate into certain tissues by endocytosis, including brain-related transport.

Vitamin B6: absorption requirements

B6 must be dephosphorylated before absorption. Alkaline phosphatase removes phosphate groups, and this enzyme is zinc-dependent. B6 is absorbed mostly by passive diffusion in the jejunum.

Vitamin B6: deficiency risk factors

B6 deficiency risk increases with alcohol use, poor intake, older age, malabsorption, certain medications, zinc deficiency, and riboflavin deficiency.

Vitamin B6: deficiency symptoms

B6 deficiency can cause seborrheic dermatitis, glossitis, cheilosis, fatigue, depression, confusion, neuropathy, seizures, and microcytic anemia.

Vitamin B6: special treatment

If B6 deficiency is caused by a medication, treatment may require B6 supplementation, usually pyridoxine. Isoniazid therapy often needs B6 to prevent neuropathy.

Folate: body functions

Folate is used for one-carbon transfer, DNA synthesis, RNA synthesis, purine synthesis, thymidylate synthesis, methionine cycle, SAM production, methylation, gene expression, and red blood cell formation.

Folate: why it is essential

Folate is essential because humans cannot fully make it. We lack the enzyme needed to connect pteridine and PABA, so folate must come from the diet.

Vitamin B12: absorption steps

B12 is released from food by HCl and pepsin, binds R protein in the stomach, R protein is broken down in the duodenum, B12 binds intrinsic factor, the B12-IF complex binds cubam receptors in the ileum, enters enterocytes, then B12 leaves bound to transcobalamin II.

Vitamin B12: R protein / haptocorrin

R protein, also called haptocorrin, protects B12 in the stomach.

Vitamin B12: intrinsic factor

Intrinsic factor is made by stomach parietal cells and is required for B12 absorption in the ileum.

Vitamin B12: cubam receptor

The cubam receptor is on the ileum brush border and takes up the B12-intrinsic factor complex into enterocytes.

Vitamin B12: transcobalamin II

Transcobalamin II carries absorbed B12 in the blood to body tissues.

Vitamin B12: haptocorrin in blood

Haptocorrin carries most circulating B12 and acts like a storage/transport pool.

Retinol: CRBPII

CRBPII binds retinol and retinal inside enterocytes and helps direct vitamin A metabolism.

Retinol: RBP

RBP, or retinol-binding protein, carries retinol from the liver through the blood to tissues.

Retinol: TTR

TTR, or transthyretin, stabilizes the RBP-retinol complex in blood and helps prevent kidney loss.

Retinol: STRA6

STRA6 is a receptor that helps target tissues take up retinol from RBP.

Carotenoids: SR-B1

SR-B1 helps carotenoids move from the GI lumen into enterocytes.

Vitamin E: SR-B1, CD36, NPC1L1

SR-B1, CD36, and NPC1L1 may help vitamin E enter enterocytes from the GI lumen.

Vitamin K: SR-B1, CD36, NPC1L1

SR-B1, CD36, and NPC1L1 may help vitamin K enter enterocytes from the GI lumen.

Vitamin E: alpha-TTP

Alpha-tocopherol transfer protein helps the liver put alpha-tocopherol into VLDL and protects it from oxidation.

Vitamin E: ABCA1

ABCA1 helps release VLDL carrying alpha-tocopherol from the liver into the blood and helps vitamin E move out of cells.

Schiff base

A Schiff base has a C=N double bond. In B6 reactions, PLP forms a Schiff base with an amino acid during transamination.

Folate: active form

The active form of folate is THF and THF derivatives.

Vitamin B12: active forms

The active forms of B12 are methylcobalamin and adenosylcobalamin.

Vitamin B6: active forms

The active forms of B6 are PLP and PMP.

Vitamin A: active forms

The important active forms of vitamin A are retinal and retinoic acid. Retinol is important for transport, and retinyl esters are important for storage.

Vitamin E: active form

The biologically active form of vitamin E is alpha-tocopherol.

Vitamin K: active form

The active form of vitamin K is the reduced vitamin K form used in gamma-carboxylation.

Folate: main functions

Folate is needed for DNA/RNA synthesis, purines, thymidylate, methionine cycle, SAM production, methylation, gene expression, and RBC formation.

Vitamin B12: main functions

B12 is needed for methionine synthase, methylmalonyl-CoA mutase, SAM production, DNA synthesis, RBC formation, and nerve/myelin function.

Vitamin B6: main functions

B6 is needed for transamination, decarboxylation, heme synthesis, glycogen breakdown, neurotransmitter synthesis, homocysteine metabolism, and immune function.

Vitamin A: main functions

Vitamin A is needed for vision, gene expression, cell differentiation, immune function, reproduction, and bone development.

Vitamin E: main functions

Vitamin E is a lipid antioxidant that protects cell membranes, especially in RBCs, brain, lungs, and other tissues vulnerable to oxidative damage.

Vitamin K: main functions

Vitamin K is needed for gamma-carboxylation of clotting factors, osteocalcin for bone, and matrix Gla protein to help prevent blood vessel calcification.

Folate deficiency vs B12 deficiency

Both can cause megaloblastic macrocytic anemia and high homocysteine. B12 deficiency also causes high methylmalonic acid and neurological damage.

Folate: deficiency connection to B12

B12 deficiency can cause a functional folate deficiency because folate gets trapped as 5-methyl THF in the methyl folate trap.

Vitamin B6: deficiency connection to riboflavin/zinc

Riboflavin is needed to help convert B6 to PLP, and zinc is needed for B6 absorption through alkaline phosphatase.

Vitamin A: deficiency connection to zinc/protein/iron

Zinc helps vitamin A transport and retinol-to-retinal conversion, protein helps carry vitamin A in blood, and iron is needed for beta-carotene conversion.

Vitamin E and vitamin K interaction

High vitamin E can interfere with vitamin K metabolism and may increase bleeding risk.

Vitamin A and vitamin K interaction

Excess vitamin A may interfere with vitamin K absorption.

Alcohol: effect on folate

Alcohol can decrease folate absorption, worsen folate status, and increase risk of folate deficiency.

Alcohol: effect on B6

Alcohol interferes with B6 conversion to PLP and increases PLP breakdown through acetaldehyde.

Alcohol: effect on fat-soluble vitamins

Alcohol-related liver or GI damage can reduce absorption, storage, and metabolism of fat-soluble vitamins.

Folate: food sources

Folate is found in leafy greens, lentils, legumes, citrus, asparagus, kidney beans, broccoli, avocado, liver, and fortified grains.

Vitamin B12: food sources

B12 is naturally found in animal foods such as meat, fish, poultry, eggs, milk, and dairy. Some plant foods are fortified.

Vitamin B6: food sources

B6 is found in fish, beef, pork, chicken, organ meats, potatoes, starchy vegetables, fortified cereals, and non-citrus fruit.

Vitamin A: food sources

Preformed vitamin A is found in liver, dairy, eggs, fatty fish, and fortified foods. Provitamin A carotenoids are found in carrots, sweet potatoes, spinach, kale, pumpkin, and other orange/green vegetables.

Vitamin E: food sources

Vitamin E is found in plant oils, wheat germ, nuts, seeds, margarine, mayonnaise, some fruits and vegetables, and small amounts in meat/fish.

Vitamin K: food sources

Vitamin K1 is found in leafy greens, broccoli, cabbage, lettuce, kale, and plant oils. Vitamin K2 is found in fermented foods and some animal foods.

Fat-soluble vitamins: general absorption

Fat-soluble vitamins need dietary fat, bile, pancreatic enzymes, mixed micelles, healthy enterocytes, chylomicrons, lymph transport, and then blood transport to tissues/liver.

Vitamin A: fat-soluble absorption

Vitamin A needs fat, bile, enzymes, micelles, enterocyte uptake, re-esterification, and chylomicron packaging.

Vitamin E: fat-soluble absorption

Vitamin E needs bile salts and micelles, then enters enterocytes and is packaged into chylomicrons.

Vitamin K: fat-soluble absorption

Vitamin K absorption improves with dietary fat, bile salts, and pancreatic enzymes, then it is packaged into chylomicrons.

Vitamin A: retinoic acid gene expression

Retinoic acid enters the nucleus and binds nuclear receptors. All-trans retinoic acid binds RAR, 9-cis retinoic acid binds RXR, and these receptor complexes bind DNA to change transcription.

Vitamin A: ISX gene

High vitamin A increases retinoic acid, which increases ISX expression. ISX lowers SR-B1 and BCO1, reducing carotenoid absorption and conversion to retinal.

Vitamin A: night blindness

Vitamin A deficiency causes night blindness because vitamin A is needed to make 11-cis-retinal, which combines with opsin to form rhodopsin in rod cells.

Vitamin A: visual cycle

Light changes 11-cis-retinal to all-trans-retinal in rhodopsin, activating transducin and starting the visual signal. The eye must regenerate 11-cis-retinal to keep seeing in dim light.

Vitamin A: liver metabolism pathway

Vitamin A enters enterocytes, retinol binds CRBPII, LRAT makes retinyl esters, retinyl esters enter chylomicrons, chylomicrons go to the liver, and the liver stores vitamin A mainly as retinyl esters.

Vitamin A: liver release pathway

When needed, the liver releases retinol bound to RBP. In blood, RBP-retinol binds TTR, and tissues take up retinol using receptors like STRA6.

Vitamin A: what happens when levels are high

High vitamin A increases ISX, lowers SR-B1 and BCO1, reduces carotenoid absorption/conversion, and excess preformed vitamin A can become toxic because it is stored.

Carotenoids: functions

Carotenoids can act as antioxidants, quench singlet oxygen, protect membranes, and some can be converted into vitamin A.

Carotenoids: provitamin A examples

Beta-carotene, alpha-carotene, and beta-cryptoxanthin can be converted into vitamin A.

Carotenoids: non-provitamin A examples

Lutein, zeaxanthin, and lycopene do not mainly act as vitamin A precursors; they mainly have antioxidant/protective roles.

Vitamin K: forms

Vitamin K1 is phylloquinone from plants. Vitamin K2 is menaquinones from bacteria, fermented foods, and some animal foods. Menadione is synthetic and can be harmful in humans.

Vitamin K: plant foods

Vitamin K1 is found in leafy greens such as spinach, kale, broccoli, cabbage, lettuce, and plant oils like soybean, canola, and olive oil.

Vitamin K: animal/fermented foods

Vitamin K2 forms are found in fermented foods like natto and in smaller amounts in salmon, milk, eggs, beef, chicken, and cheese.

Vitamin K: deficiency risk factors

Vitamin K deficiency risk increases in newborns, chronic antibiotic use, fat malabsorption, liver disease, gallbladder/bile problems, pancreatic disease, warfarin use, and older age.

Vitamin K: newborn deficiency risk

Newborns are at risk because little vitamin K crosses the placenta, breast milk is low in vitamin K, and their gut bacteria are not established yet.

Vitamin K: blood clotting function

Vitamin K activates clotting proteins by gamma-carboxylating glutamic acid residues, allowing clotting factors to bind calcium and work properly.

Vitamin K: clotting factors

The 4 main vitamin K-dependent clotting factors are II, VII, IX, and X.

Vitamin K: warfarin

Warfarin blocks vitamin K recycling, so reduced vitamin K cannot be regenerated and clotting factors cannot be properly activated.

Folate: deficiency disease

Folate deficiency causes megaloblastic macrocytic anemia, high homocysteine, FIGLU buildup, fatigue, glossitis, and neural tube defect risk in pregnancy.

Vitamin B12: deficiency disease

B12 deficiency causes megaloblastic macrocytic anemia, high homocysteine, high methylmalonic acid, neuropathy, demyelination, memory issues, and abnormal gait.

Vitamin B6: deficiency disease

B6 deficiency causes dermatitis, glossitis, cheilosis, neuropathy, seizures, depression/confusion, and microcytic anemia.

Vitamin A: deficiency disease

Vitamin A deficiency causes night blindness, xerophthalmia, Bitot spots, dry skin, poor growth, infection risk, and blindness in severe cases.

Vitamin E: deficiency disease

Vitamin E deficiency causes hemolytic anemia, ataxia, peripheral neuropathy, muscle weakness, and poor membrane protection.

Vitamin K: deficiency disease

Vitamin K deficiency causes poor clotting, easy bleeding, hemorrhage, intracranial bleeding in infants, and increased bone/fracture risk.

Folate: who is at risk

People at risk for folate deficiency include pregnant people, lactating people, people with alcohol use, malabsorption, low intake, or certain medications.

Vitamin B12: who is at risk

People at risk for B12 deficiency include vegans, older adults, people with low stomach acid, pernicious anemia, gastric bypass, ileal disease, metformin use, and PPI/H2 blocker use.