Know the major vitamins and their basic deficiencies and overdoses
Vitamin is short for "vital amine"- they are vital because we can't synthesise them ourselves. Most vitamins are used in metabolic processes, but do not contribute energy (unlike carbs, fats and proteins).
As for the basic deficiencies and overdoses, I'm just going to link you straight to my lecturer's source: https://en.wikipedia.org/wiki/Vitamin
And yes, I just linked you to Wikipedia.
Know that vitamin B1, B2 and B3 are very important in basic cell function
Before going through B1, B2 and B3 specifically, I'm going to give a quick rundown of some of the more common B-vitamins and what they do.
- B1 (thiamine): Co-enzyme in catabolism of sugars and amino acids.
- B2 (riboflavin): Precursor of FAD and FMN.
- B3 (niacin): Precursor of NAD and NADP.
- B5 (pantothenic acid): Precursor of coenzyme A (CoASH).
- B6 (pyridoxine): Co-enzyme in many enzymatic reactions (such as transamination).
- B7 (biotin): Co-enzyme for carboxylase enzymes in fatty acid synthesis and gluconeogenesis.
- B9 (folic acid): I'll talk more about this one in the second half of this post.
- B12 (cobalamins): Co-enzymes involved in processes such as DNA synthesis, fatty acid metabolism and amino acid metabolism.
Now back to B1, B2 and B3! B1, B2 and B3 are precursors for three of the co-factors associated with pyruvate dehydrogenase. More specifically, B1 can become thiamin diphosphate, B2 can become FAD and B3 can become niacin. As B1, B2 and B3 are important, there are a range of symptoms associated with their deficiency:
- B1 deficiency: Beriberi, abnormal blood sugar, depression, fatigue, vomiting, GI disorders
- B2 deficiency: Light sensitivity, cracks/inflammation of the mouth, dizziness, insomnia
- B3 deficiency: Pellagra (dementia, death), nausea, vomiting, fatigue, dermatitis, loss of appetite, swollen red tongue. B3 deficiency may also increase the risk for some skin cancers.
Understand the forms of folate and its roles,
particularly 1-carbon metabolism and neural tube
development
Folate is also known as pteroyl-glutamate, as it consists of a folyl moiety with glutamate attached. We cannot synthesise it: it is formed in microbes from GTP. Folate can be found in many forms, such as folylpolyglutamates (a folyl moiety with 5-6 glutamates attached). Glutamate moieties can be added to folylpolyglutamates by folylpolyglutamate synthase (FPGS), and folate with only one glutamate can have that glutamate removed by glutamate carboxypeptidase 2 to form pteroate and glutamate. Folylpolyglutamates also serve as a storage form of folate in humans. (Google Chrome is giving me so many red squiggly lines right now...)
Folate is important in the transfer of methyl groups. To understand how that works, we need to meet SAM, or S-adenosyl-L-methionine. Remember how I said that methionine is a vital source of methyl groups? Well, S-adenosyl-L-methionine can donate its methyl group to something that needs it, resulting in S-adenosyl-L-homocysteine (SAH). This can be converted to L-homocysteine. In order to restore methionine and then S-adenosylmethionine, a methyl group must be returned. Methyl-H4 folate returns methyl groups to homocysteine to regenerate methionine, keeping the cycle going. Without this process, SAM would struggle to methylate all of the things that it normally does, including the DNA. (Yup, it methylates DNA, which affects gene transcription.)
Folate is also important in various stages of purine and pyrimidine synthesis. Methylene-H4 folate is a cofactor in both purine and pyrimidine synthesis, and 10-formyl H4 folate is important in purine synthesis. These pathways can be blocked by certain inhibitors such as 5-FU (5-fluorouracil) and MTX (methotrexate).
5-FU binds covalently to thymidylate synthase, blocking thymine production from dUMP. (This is one of the processes that methylene-H4 folate) is involved in.) Some dUMP can be shunted to dUTP, which can be used instead of dTTP, but can cause irreparable double-strand breaks.
Following the thymidylate synthase process, methylene-H4 folate is converted to H2 folate, which is then converted into H4 folate. This latter step (H2 folate to H4 folate) can be blocked by MTX. Low doses of this drug can actually be helpful in treating autoimmune diseases.
Folate is also known as pteroyl-glutamate, as it consists of a folyl moiety with glutamate attached. We cannot synthesise it: it is formed in microbes from GTP. Folate can be found in many forms, such as folylpolyglutamates (a folyl moiety with 5-6 glutamates attached). Glutamate moieties can be added to folylpolyglutamates by folylpolyglutamate synthase (FPGS), and folate with only one glutamate can have that glutamate removed by glutamate carboxypeptidase 2 to form pteroate and glutamate. Folylpolyglutamates also serve as a storage form of folate in humans. (Google Chrome is giving me so many red squiggly lines right now...)
Folate is important in the transfer of methyl groups. To understand how that works, we need to meet SAM, or S-adenosyl-L-methionine. Remember how I said that methionine is a vital source of methyl groups? Well, S-adenosyl-L-methionine can donate its methyl group to something that needs it, resulting in S-adenosyl-L-homocysteine (SAH). This can be converted to L-homocysteine. In order to restore methionine and then S-adenosylmethionine, a methyl group must be returned. Methyl-H4 folate returns methyl groups to homocysteine to regenerate methionine, keeping the cycle going. Without this process, SAM would struggle to methylate all of the things that it normally does, including the DNA. (Yup, it methylates DNA, which affects gene transcription.)
Folate is also important in various stages of purine and pyrimidine synthesis. Methylene-H4 folate is a cofactor in both purine and pyrimidine synthesis, and 10-formyl H4 folate is important in purine synthesis. These pathways can be blocked by certain inhibitors such as 5-FU (5-fluorouracil) and MTX (methotrexate).
5-FU binds covalently to thymidylate synthase, blocking thymine production from dUMP. (This is one of the processes that methylene-H4 folate) is involved in.) Some dUMP can be shunted to dUTP, which can be used instead of dTTP, but can cause irreparable double-strand breaks.
Following the thymidylate synthase process, methylene-H4 folate is converted to H2 folate, which is then converted into H4 folate. This latter step (H2 folate to H4 folate) can be blocked by MTX. Low doses of this drug can actually be helpful in treating autoimmune diseases.
Know the daily requirements for folate and disorders
related to under supply
The daily requirements for folate are as follows:
The daily requirements for folate are as follows:
- Children: 150-200 μg/day
- Teenagers: 300-400 μg/day
- Adults: 400 μg/day
- Pregnancy: 600 μg/day
- Lactation: 500 μg/day
Folate can be found in foods such as yeast spreads (vegemite!), fortified cereals and some beans. Flour is often fortified with folate, making folate deficiency rare in the Western diet, unless you're an alcoholic (alcoholism can cause malabsorption). If folate is deficient, its derivatives (methionine, nucleotides etc.) can be deficient too, and homocysteine can build up.
Perhaps the most well-known effect of folate deficiency is spina bifida, which is when the neural tube fails to close. I've blogged more about it here. Later in life, folate deficiency can cause megaloblastic anaemia, in which early erythroblasts do not divide, resulting in a deficiency of red blood cells. Hyperhomocysteinemia as a result of folate deficiency may also increase the risk of cardiovascular disease.
Perhaps the most well-known effect of folate deficiency is spina bifida, which is when the neural tube fails to close. I've blogged more about it here. Later in life, folate deficiency can cause megaloblastic anaemia, in which early erythroblasts do not divide, resulting in a deficiency of red blood cells. Hyperhomocysteinemia as a result of folate deficiency may also increase the risk of cardiovascular disease.
Why smoking is a problem
Aside from the obvious lung problems, smoking can also lower the levels of many vitamins. These include β-carotene (a precursor to vitamin A) and vitamins B6, B9, B12, C, D and E. As B9 is folic acid, and deficiencies of folic acid can lead to neural tube defects, smoking can also lead to neural tube defects. In fact, even exposing non-smoking pregnant women to secondhand smoke can increase the rates of neural tube defects.
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