Introduction to Genetics and Lipid Metabolism
Lipid Anabolism
Lipid anabolism involves three main processes: the synthesis of fatty acids, glycerol, and triacylglycerols.
Fatty Acid Synthesis
Fatty acid synthesis occurs in the cytosol from acetyl-CoA. This process is connected to carbohydrate catabolism, β-oxidation, and amino acid catabolism. Acetyl-CoA serves as the initiator. The first step involves transferring acetyl-CoA to a 3-carbon activator, malonyl-CoA. The addition of a malonyl-CoA molecule results in a 4-carbon chain and releases CO2. Subsequently, two hydrogenation reactions occur, consuming NADPH. This process is catalyzed by a complex of enzymes called fatty acid synthetase (FAS). The repeated addition of malonyl-CoA molecules allows for the addition of two carbons in each step. The growing fatty acid chain remains attached to the FAS complex. The biosynthesis of fatty acids differs from β-oxidation in that it occurs in the cytosol, not the mitochondria. Additionally, the growing fatty acid chain remains attached to the FAS complex and not to CoA. The NADPH used in fatty acid synthesis comes from the pentose phosphate pathway and NADH or FADH2.
Glycerol Synthesis
Glycerol has three carbons that can bind to fatty acids. To do this, it must be in the form of glycerol-3-phosphate. This is obtained from dihydroxyacetone-3-phosphate, which is formed during glycolysis, or from glycerol released during fat hydrolysis.
Triglyceride Synthesis
Triglyceride synthesis requires glycerol-3-phosphate and fatty acyl-CoA. The fatty acyl-CoA is obtained from synthesized fatty acids and coenzyme A. Fatty acid molecules form ester bonds with glycerol, first forming monoacylglycerols, then diacylglycerols, and finally triacylglycerols. This process occurs in all cells, especially in liver and adipose tissue cells, where triglycerides serve as energy storage.
Amino Acid Anabolism
Humans have 10 amino acids that we cannot synthesize ourselves (essential amino acids) and 10 that we can (non-essential amino acids). Each species has a different set of essential amino acids. Microorganisms can synthesize all amino acids, while others have lost the ability to synthesize some during evolution. Amino acid synthesis starts with a 3- or 5-carbon organic acid. An amino group is then added, which can be obtained from other amino acids (transamination) or from a free ammonium ion released from an amino acid that has lost its amino group (deamination). Some bacteria and cyanobacteria can also use N2 as a source to synthesize amino groups. The synthesis of the essential amino acid α-ketoglutaric acid, a component of the Krebs cycle, involves combining it with NH4+ to form glutamic acid. This amino acid is essential because it donates its amino group to other molecules during biosynthesis. The biosynthesis of other essential amino acids also depends on this process.
Mendelian Genetics
Mendel studied traits that are inherited and those that are not (acquired traits). Acquired traits are influenced by environmental factors and can be modified throughout life. Mendel introduced the concepts of phenotype (the observable characteristics of an organism, which depend on the genotype and environment) and genotype (the set of genes inherited from parents).
Gene: A segment of DNA that contains the information to determine a biological trait. It is also called a hereditary factor. In viruses, genes can be DNA or RNA segments.
Allele: The different variations that a gene can have.
Mendel’s Laws
1st Law: Law of Uniformity of F1 Hybrids: When crossing purebred plants with smooth seeds and purebred plants with wrinkled seeds, the first filial generation (F1) was uniform, with all plants having smooth seeds.
2nd Law: Law of Segregation of Characters: When crossing F1 plants, the second generation (F2) had both smooth and wrinkled seeds in a 3:1 ratio. Mendel deduced that the factor controlling this trait was doubled, with one inherited from each parent. F1 plants had two different factors, but only one was expressed (dominant). Recessive factors are only expressed in the absence of the dominant factor. When F1 plants are crossed, each parent produces gametes with either the dominant (L) or recessive (l) factor. The resulting combinations are LL, Ll, and ll. The 2nd law explains the segregation of characters during inheritance.
3rd Law: Law of Independent Assortment of Characters: Mendel studied the inheritance of two characters: seed shape and color. He chose two purebred plants, one with smooth yellow seeds and one with wrinkled green seeds. The F1 generation was uniform, with smooth yellow seeds, indicating that yellow was dominant. When crossing F1 plants, the F2 generation had 315 smooth yellow seeds, 108 smooth green seeds, 101 wrinkled yellow seeds, and 32 wrinkled green seeds. Mendel deduced that the factors determining each character were inherited independently of each other. This is the 3rd law, the law of independent assortment of characters.
Sex-Linked Inheritance
During meiosis, homologous chromosomes (carrying the same genes) pair up. These areas are called homologous segments. The rest of the chromosomes carry their own genes (differential segments). The X and Y chromosomes have differential segments. In males, if the X chromosome carries a recessive allele, the male is hemizygous. All genes located on the differential segments of the X and Y chromosomes are sex-linked. Examples of X-linked recessive traits include hemophilia, color blindness, and night blindness. Ichthyosis is linked to the differential segment of the Y chromosome.