Biochemistry-II - Amino Acid Metabolism Carbon - Quick Guides | Biochemistry

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Study GuideBiochemistry-II–Amino Acid Metabolism:Carbon1.1-Carbon MetabolismIn our cells, many important reactions involve moving tiny chemical pieces called1-carbon units(like–CH₃,–CH₂–, or–CHO). These reactions are called1-carbon metabolism.To make them work, the body mainly depends on two helpers (cofactors):•Folic acid (folate)•Vitamin B₁₂Together, they help build DNA, RNA, amino acids, membrane lipids, and neurotransmitters. In otherwords, they support growth, repair, and normal cell function.Folic Acid: The Carrier of One-Carbon UnitsWhy folic acid is importantFolic acid helps the cellactivate, carry, and transfer single-carbon groups. These reactions areessential for:•Amino acid metabolism•DNA and RNA synthesis•Making membrane lipids•Producing neurotransmittersSome medicines even target folic acid metabolism to stop cancer cells or bacteria from growing.Structure of folic acidFolic acid is made ofthree parts:1.Pteridine ring (6-methylpterin)2.p-Aminobenzoic acid (PABA)3.Glutamic acid

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Study GuideTheglutamic acid partdoes not take part directly in reactions. Instead, cells often attach severalglutamates (3–8 of them) to folate. This forms a negatively charged “handle” that keeps folate insidethe cell and helps it bind to enzymes.Thepteridine and PABA partsare the ones that actually do the chemistry.Figure 1Activating folic acidBefore folic acid can work, it must bereduced twice by NADPHinside the cell.•The pyrazine ring of the pteridine portion gets reduced.•After two reductions, folic acid becomes:Tetrahydrofolate (THF)THF is theactive formthat accepts and carries 1-carbon units.

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Study GuideHow THF carries carbon unitsTetrahydrofolate usually accepts a carbon group fromserine(and sometimes from glycine).This produces the key compound:N⁵,N¹⁰-methylene-tetrahydrofolateThink of this as thecentral hubof 1-carbon metabolism.Figure 2

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Study GuideDifferent forms, different jobsN⁵,N¹⁰-methylene-THF can change into other forms depending on what the cell needs:•Methylene form→ used to makethymidine (dTMP)for DNA.•Methenyl / formyl form→ used inpurine synthesisfor DNA and RNA.•Methyl form→ used to makemethionine.So, folate doesn’t just carry carbon—it adjusts the form of carbon for different pathways.Folate Antagonists: Sulfa DrugsSome drugs stop bacteria by blocking folate metabolism.Example: SulfanilamideSulfanilamide looks very similar top-aminobenzoic acid (PABA).Because of this similarity:•Bacteria mistakenly use sulfanilamide.•They can’t make folic acid properly.•Their growth is stopped.These are calledsulfa drugsand were among the firstantimetabolitesused to treat infections.Humans are safe becausewe do not synthesize folic acid—we get it from food—so the drugmainly harms bacteria, not us.

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Study GuideFigure 3Vitamin B₁₂: A Critical PartnerVitamin B₁₂takes part in onlytwo reactions, but they areessential for life.People who cannot absorb B₁₂developpernicious anemia, which is treated today with B₁₂injections.Structure of vitamin B₁₂Vitamin B₁₂contains:•Acobalt (Co) ion•Bound inside a ring structure•The cobalt makes six bonds:oFour to the ring nitrogensoOne to a nitrogen of dimethylbenzamidineoOne to eithercyanide(vitamin form) oradenosine(active coenzyme)This cobalt is what allows B₁₂to carry and transfer methyl groups.Role in fatty acid metabolismVitamin B₁₂is needed for the enzyme:

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Study GuideMethylmalonyl-CoA mutaseThis enzyme is important when breaking down:•Odd-chain fatty acids•Branched-chain amino acidsOdd-chain fats producepropionyl-CoA, which becomesmethylmalonyl-CoA.With the help of B₁₂, methylmalonyl-CoA is converted into:Succinyl-CoASuccinyl-CoA enters theKrebs cycleto produce energy.Figure 4Role in methionine synthesisVitamin B₁₂also helps makemethionine.Steps:1.5-methyl-THFgives a methyl group to B₁₂.2.B₁₂holds the methyl group on cobalt.3.B₁₂transfers it tohomocysteine.4.Homocysteine becomesmethionine.Methionine is important for proteins and for donating methyl groups.

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Study GuideMethyltransferases and SAMMost methyl transfers use methionine through a special molecule:S-adenosylmethionine (SAM)SAM is made from:•Methionine•ATPAll three high-energy phosphate bonds of ATP are used.Why SAM works so wellMethyl transfer from SAM is very favorable because:•The positive charge on sulfur is relieved.•The bond to adenosine breaks easily.•The leftover product (S-adenosyl-homocysteine) is quickly removed.This is important because S-adenosyl-homocysteine canblock methyltransferasesif it builds up.

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