In biology, a macromolecule refers to any agglomerate or polymer made up of smaller building blocks, or monomers. Traditionally, the study of biological macromolecules was highly compartmentalized. While some scientists devote their entire careers to the study of specific proteins, carbohydrates, lipids or nucleic acids, the advent of the Human Genome Project and widely accessible online databases in the 1990s changed all of that. Today, the walls separating biochemistry, cell biology, genetics and even biophysics have largely crumbled. This article will provide a brief overview of each macromolecule and describe its major roles in cell biology and human physiology.
Proteins
In humans and other organisms, proteins are composed of 20 kinds of amino acids. Humans must obtain half of these amino acids from the diet, including phenylalanine, valine, threonine, tryptophan, isoleucine, methionone, histidine, arginine, leucine and lysine. The first letters of each of these so-called essential amino acids form the mnemonic “PVT TIM HALL.”
The sequence of amino acids specifies the primary structure of a certain polypeptide (or protein). Proteins range from about a dozen to several thousand amino acids in length. Because the number of potential amino acid combinations is determined by 20 to the power of n, the variety of proteins that can be produced is nearly limitless.
Proteins are the workhorse of structure and function in all known cells. This is also true on the tissue and organ levels. A few examples of structural proteins include actin microfilaments and microtubules at the cellular level; at the macroscopic level, myosin is a key component of muscle fibers, and collagen serves as the scaffold in skin, teeth and bones.
Examples of purely functional proteins include the enzymes that catalyze thousands of chemical reactions in our bodies; hemoglobin to transport oxygen in the bloodstream; neurotransmitters such as endorphins; protein hormones such as insulin; ion channel pumps to conduct nerve impulses; and immunoglobulins, a.k.a. antibodies, which are a major branch of the specific immune response.
Carbohydrates
More kinds of sugars exist than any other type of biological polymer. The two most common polysaccharide polymers are cellulose, long rigid strands of glucose more familiar to us as wood; and chitin, a polymer of N-acetylglucosamine found in the shells of crustaceans.
In humans, most carbohydrates are either metabolized for energy or converted to fat for long term energy storage. Some glucose is converted to starch, or glycogen, a branched polymer found in the liver and skeletal muscles. The body stores enough glycogen to meet its glucose needs for approximately 24 hours.
Some carbohydrates are attached to proteins. Scientists think this accomplishes two things. First, sugars may extend the life span of a given protein by blocking its degradation by protease enzymes. Second (and arguably more important), sugars act as intracellular address labels, directing the protein to its appropriate destination (e.g., the cell nucleus, mitochondria, plasma membrane or other organelle).
Because humans can synthesize glucose from amino acid precursors and, in turn, convert glucose into other sugars (fructose, mannose, ribose) there is no such thing as an “essential sugar” in human physiology.
Lipids
When the word “lipid” is mentioned, the first image that comes to mind is fat. Although this is true, lipids encompass a variety of other molecules, including steroid hormones and bile acids, both derived from cholesterol, as well as signaling molecules such as inositol triphosphate, prostaglandins, thromboxanes and leukotrienes.
From a macromolecular perspective, most lipids fall into three categories: triacylglycerols stored in adipocytes (fat cells); diacylglycerols found in all cell membranes; and sphingomyelin, an abundant component of the myelin sheath surrounding neuronal axons throughout the human nervous system. Adipose tissue serves as the main energy reservoir in periods of starvation. Gram for gram, fatty acids yield nearly three times as much energy in the form of ATP as do proteins or carbohydrates. As with amino acids, certain fatty acids (e.g., omega-3 fatty acids) are considered essential because humans must obtain them from their diet.
Nucleic Acids
DNA (deoxyribonucleic acid)
Nowadays it is common knowledge that genes are made of DNA. Surprisingly, it took biologists the first half of the 20th century to arrive at this conclusion. Until the 1920s, relatively little was known about the components of DNA or the central role DNA plays in determining hereditary traits. Building on the work of several scientists, especially the X-ray diffraction studies of Rosalind Franklin and chemical analyses of Erwin Chargaff, James Watson and Francis Crick proposed their double helical model of DNA in 1953.
In the Watson-Crick model, each strand of DNA is composed of a backbone formed of deoxyribose sugars linked together by phosphodiester bonds. A nitrogenous base is attached to each sugar–either a two-ringed purine, adenine (A) or guanine (G) or a single ringed pyrimidine-thymine (T) or cytosine (C). Each base pairs with a complementary base such that A pairs with T and G pairs with C. Two complementary DNA strands wrap around each other to form a structure called an anti-parallel double helix. The two DNA strands are held together by numerous hydrogen bonds that form between their respective base pairs.
A decade after Watson and Crick’s discovery, three teams of scientists cracked the genetic code. Essentially, they discovered that in almost all organisms, DNA is read as a non-overlapping triplet code, in which each unit of three bases corresponds to one amino acid. This unit (when transcribed into messenger RNA) is called a codon. Except for tryptophan and methionine, all other amino acids are specified by anywhere from two to six different codons. Three codons (UAG, UGA and UGG) do not code for any amino acid. Instead, they serve as stop signals that terminate protein translation.
RNA (ribonucleic acid)
RNA is similar to DNA in some respects. It is composed of a sugar-phosphate backbone and contains three of the same bases as DNA (adenine, guanine and cytosine). Instead of thymine, however, RNA contains uracil, which is chemically identical to thymine except that it lacks a methyl group. Another difference is that DNA remains confined to the nucleus (in eukaryotic cells) whereas RNA is transcribed in the nucleus then departs into the cytosol. Finally, in contrast to DNA, cells contain several distinct types of RNA, including messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), and, in eukaryotes, small nuclear RNA (snRNA).
As far as their roles go, mRNA carries the message encoded in DNA to the ribosome for translation into protein. Transfer RNA acts as a tow truck hauling each amino acid to the ribosome. Ribosomes themselves are large complexes of peptides and ribosomal RNA that assemble amino acids into new proteins. Finally, snRNA is confined to the nucleus and helps process mRNA into its mature form.
Many scientists are convinced that primitive cells used RNA as their genetic material before DNA became the dominant nucleic acid. Two main lines of evidence for this theory are the following: 1) Certain viruses including influenza and HIV contain genomes made entirely of RNA. Viruses may have originated as rogue genetic elements that broke away from their parent cells and somehow acquired the ability to infect other cells. 2) Unlike DNA, certain types of RNA have catalytic abilities. Small nuclear RNA splices mRNA by removing sequences called introns then rejoins the remaining exons before the mature mRNA is allowed to exit the nucleus. Ribosomal RNA catalyzes the formation of peptide bonds, performing the fundamental step of protein synthesis. Scientists sometimes call RNA-based catalysts “ribozymes” in contrast to enzymes, which are made of protein.
