lipids + nucleotides

De novo biosynthesis

The synthesis of nucleotides "from scratch" using basic molecular precursors; conserved across all species because nucleotides are essential

Salvage pathway

A nucleotide synthesis pathway that recycles free bases from degradation or diet by attaching them to ribose; more energy-efficient than de novo synthesis

PRPP (phosphoribosyl pyrophosphate)

An activated ribose-5-phosphate molecule with a pyrophosphate leaving group used as a key substrate in nucleotide biosynthesis

Pyrophosphate

A high-energy leaving group derived from ATP that activates ribose-5-phosphate for nucleotide synthesis

Ribose-5-phosphate

A pentose sugar precursor used to form PRPP and ultimately nucleotides

Pyrimidine synthesis strategy

Pyrimidine bases are synthesized first and then attached to ribose (PRPP)

Purine synthesis strategy

Purine bases are synthesized directly on the ribose (PRPP) backbone

Ribonucleotide reductase

Enzyme that converts ribonucleotides into deoxyribonucleotides by removing an -OH group from the ribose

Carbamoyl phosphate

A key intermediate in pyrimidine synthesis that is also used in other metabolic pathways

Carbamoylaspartate

Product formed from carbamoyl phosphate in the committed step of pyrimidine synthesis

Committed step (pyrimidine synthesis)

The conversion of carbamoyl phosphate to carbamoylaspartate

Orotate

A cyclized intermediate that represents the completed pyrimidine base before attachment to ribose

Orotate + PRPP reaction

The step where the pyrimidine base attaches to the C1 of PRPP to form a nucleotide

Inosinate (IMP)

A purine intermediate that serves as the precursor for AMP and GMP synthesis

IMP conversion

The process by which inosinate is converted into either AMP or GMP depending on cellular needs

5-phosphoribosylamine

The first committed intermediate in purine synthesis formed from PRPP and glutamine

Committed step (purine synthesis)

The conversion of PRPP into 5-phosphoribosylamine

Glutamine (purine synthesis role)

Provides the nitrogen required to initiate purine ring formation on PRPP

Thymine synthesis overview

Conversion of dUMP to dTMP by adding a methyl group to uracil

dUMP

Deoxyuridine monophosphate; precursor molecule for thymine synthesis

dTMP

Deoxythymidine monophosphate; the thymine-containing nucleotide used in DNA

Thymidylate synthase

Enzyme that catalyzes conversion of dUMP to dTMP using a methyl donor

N⁵

N¹⁰-methylene tetrahydrofolate

1C donor

A molecule that donates a single carbon unit in biosynthetic reactions

Dihydrofolate reductase (DHFR)

Enzyme that regenerates tetrahydrofolate from dihydrofolate

Fluorouracil (5-FU)

A chemotherapy drug that inhibits thymidylate synthase by mimicking dUMP

Mechanism of fluorouracil toxicity

Forms a stable complex with thymidylate synthase

Side effects of fluorouracil

Hair loss and nausea due to targeting rapidly dividing cells

Folate deficiency consequence

Leads to uracil incorporation into DNA due to lack of thymine synthesis

Urate

Final product of purine degradation in humans that is excreted in urine

Gout

A condition caused by accumulation and crystallization of urate in joints

Xanthine

A purine degradation intermediate that may accumulate but is less likely to crystallize than urate

Purine-rich foods

Foods like red meat and tofu that can increase urate levels when consumed excessively

Triglyceride (triacylglycerol)

A storage lipid composed of glycerol and three fatty acids

Membrane lipids

Lipids with polar head groups that form biological membranes

Glycerol-3-phosphate

The common precursor molecule for both triglycerides and phospholipids

Acyl-transferases

Enzymes that attach fatty acid chains to glycerol-3-phosphate

Phosphatidate

A key intermediate formed after two fatty acids are added to glycerol-3-phosphate

Triglyceride synthesis

Involves dephosphorylation and acylation of phosphatidate to form triacylglycerol

Phosphatidate activation

Reaction of phosphatidate with CTP to form CDP-diacylglycerol

CDP-diacylglycerol

An activated intermediate that reacts with alcohols to form membrane phospholipids

Alcohol activation (lipid synthesis)

Activation of an alcohol using ATP and CTP to allow formation of phospholipids

Phosphatidylcholine

The most abundant phospholipid in mammalian membranes

Phosphatidylethanolamine conversion

A pathway that produces phosphatidylcholine when choline is deficient

Sphingolipids

Membrane lipids that use a ceramide backbone instead of glycerol

Ceramide

The structural backbone of sphingolipids and glycolipids

Gangliosides

Glycolipids containing sugar groups attached to ceramide

Tay-Sachs disease

A disorder caused by failure to degrade gangliosides

Acetyl-CoA (cholesterol synthesis)

The primary precursor molecule for cholesterol biosynthesis

Acetoacetyl-CoA

Formed from two acetyl-CoA molecules during early cholesterol synthesis

HMG-CoA

Intermediate formed from acetoacetyl-CoA and acetyl-CoA in cholesterol synthesis

HMG-CoA reductase

The rate-limiting and committed step enzyme converting HMG-CoA to mevalonate

Mevalonate

A committed intermediate in cholesterol synthesis that cannot revert back to acetyl-CoA

Squalene

A 30-carbon intermediate formed from multiple 5-carbon units during cholesterol synthesis

Cholesterol

A lipid molecule essential for membrane structure and precursor for steroid hormones and vitamins

Lipoproteins

Spherical particles that transport lipids and cholesterol in the bloodstream

Apolipoproteins

Protein components of lipoproteins that help bind and transport lipids

Chylomicrons

Largest and least dense lipoproteins that transport dietary fats

VLDL (very low-density lipoprotein)

Lipoprotein that transports triglycerides from liver to tissues

LDL (low-density lipoprotein)

“Bad cholesterol” that delivers cholesterol to tissues and contributes to plaque formation

LDL receptor

Cell surface receptor that allows uptake of LDL particles into cells

Foam cells

Lipid-loaded macrophages formed from oxidized LDL

Atherosclerosis

Disease characterized by plaque buildup in arteries due to lipid accumulation

HDL (high-density lipoprotein)

“Good cholesterol” that transports cholesterol back to the liver for disposal

Statins

Drugs that inhibit HMG-CoA reductase

Cholesterol regulation

Controlled by enzyme activity

Cholesterol as precursor

Required for synthesis of steroid hormones and certain vitamins

Trimethylamine-N-oxide (TMAO)

A metabolite associated with high choline intake and increased risk of atherosclerosis