Physiology, Proteins


Introduction

Proteins are biopolymeric structures composed of amino acids, of which there are 20 commons found in biological chemistry. Proteins serve as structural support, biochemical catalysts, hormones, enzymes, building blocks, and initiators of cellular death. Proteins can be further defined by their four structural levels: primary, secondary, tertiary, and quaternary.

The first level is the primary structure because it is the most basic level of protein structure. It is composed of the linear order of amino acid residues. All of the residues connect via peptide bonds. These linkages have designated carbon atom positions of alpha, beta, and gamma, which correspond to specific positions relative to the peptide linkage. This structure also has the name of the protein backbone.

The second level of protein structure is the secondary structure, and it consists of the various shapes form via hydrogen bonding. These shapes include alpha helix, beta-pleated sheet, and beta-turn. As previously stated, hydrogen bonds stabilize all of these shapes.

The third level of protein structure is the tertiary structure. It consists of the three-dimensional shape that will form when the polypeptide chain "backbone" interacts with an aqueous environment, which immediately begins to form when a newly synthesized polypeptide chain exits the terminal end of the ribosomal subunit complex. The polypeptide chain sequesters hydrophobic residues and exposes those that are hydrophilic; this is all to achieve thermodynamic stability. This thermodynamic stability is further driven by a variety of chemical interactions to include hydrogen bonds, Vanderwall forces, and ionic bonding (the term ionic bonding includes electrostatic interactions and salt bridges). The energy that these interactions can produce ranges from 0.1 to 3 kilocalories per mole. The fourth and final level of protein structure is called the quarternary structure. This level is when complexes form from multiple polypeptide chains called subunits. An example of this is hemoglobin and how its tetrameric structure forms when two alpha and two beta subunits are held together by chemical interactions. Therefore it is appropriate to say that quaternary structure is the three-dimensional arrangement of two or more polypeptides in a protein, each of which folds independently of the other. It is important to note that the term subunit is interchangeable with protomer.[1] An example of the clinical significance is in sickle cell anemia, whereby the hemoglobin protein made possesses amino acids that are insoluble in an aqueous environment, driving the defective hemoglobin to aggregate to hide newly formed hydrophobic residues and achieve thermodynamic favorability. These altered hemoglobin molecules then form polymers that manifest as long, inflexible rods. These macromolecules continue to elongate until they eventually precipitate and distort the red blood cell's plasma membrane into the classic sickle shape seen in a sickle cell crisis.

Issues of Concern

Denaturation

Mercaptoethanol is a chemical that can break up disulfide bonds. It "cuts" proteins to the right of the penultimate amino acid's carboxyl group. This cutting can only occur at disulfide bonds because these bonds can receive electrons from the alcohol groups on beta-mercaptoethanol, which is also why this substance is known as a reducing agent. The issue of concern manifests through hormonal denaturation. Hormones are well-known for being proteins with a lot of disulfide bonds. Therefore if placed in an aqueous environment rich in alcohol groups, hormones will denature and lose biological functionality. This condition appears to be why mothers who have alcohol use disorder and breastfeed can stop lactating (due to denatured prolactin), why alcoholics develop diabetes after a while (due to denatured insulin), and why teenagers who excessively consume alcohol stop growing (due to denatured growth hormone).[2]

Cellular

Transportation

Proteins, produced on ribosomes in the rough endoplasmic reticulum, are transferred to the smooth endoplasmic reticulum to be processed into vesicles for intracellular transport. Proteins are also responsible for targeting the vesicles through a series of interactions, which include receptor and substrate interactions. The Golgi apparatus is made up of the cis, medial, trans, and trans-Golgi network. James Rothman proposed in the 1980s that proteins processed by the Golgi apparatus are transported from one sac to the next in vesicles. This concept is important because it was not well understood how proteins could stay and act as Golgi specific enzymes, especially since virtually all Golgi enzymes are membrane proteins. This proposal led to three different theorized pathways by which proteins are processed and transported.[3]

The three pathways are:

  • Secretory
  • Lysosomal
  • Regulated

Secretory Transport

Constitutive secretion is a continuous pathway that takes place in all cells. It is thought to be how cells produce new plasma membranes. It's also how exocytosis occurs. Vesicles in the cytosol fuse with the plasma membrane. Fluid membranes facilitate membrane fusion because of the principle that "like dissolves like." This theory asserts that a signal and a complement receptor (which is on the Golgi) are necessary for sorting in the Golgi. This theory derives from the well-established concept that a signal and its complement receptor are fundamental components of all intracellular vesicular sorting. [4]

Lysosomal Transport

Defined as the constitutive lysosomal pathway, this theory asserts that transport vesicles containing lysosomal enzymes form a lysosome when intracellular vesicles fuse vesicles formed from the plasma membrane during endocytosis. The lysosome is the site within a cell where macromolecules degrade into their respective monomers. (e.g., proteins, polysaccharides, polynucleotides, and lipids. These are the basic building blocks: amino acids, monosaccharides, nucleotides. There is no single building block for lipids, but fatty acids come closest. The cell reuses building blocks to make new macromolecules.[5] 

Regulated Transport

This regulated secretory pathway only takes place in cells specialized for secretion. (e.g., B lymphocytes secrete antibodies). Vesicle containing specialized proteins for secretion bud off of the trans-Golgi network region of the Golgi apparatus. The secretory vesicle then remains in the cytosol. The ligand binds to a ligand-binding site on the extracellular matrix facing transmembrane receptor protein. After binding to a ligand (e.g., neurotransmitter or hormone), this causes the receptor to undergo a conformational change, thus activating the signal transduction pathway. The signal transduction pathway could cause an increase in intracellular calcium levels. The extracellular concentration of calcium is 1x10(^-3). Intracellular calcium concentration is 1x10(^-7). Calcium influx activates the cell once intracellular concentration reaches 5x10^(-6)M. The cytosolic secretory vesicles then move to the plasma membrane for exocytosis.[6]

Peptide Bonds

Peptide bonds form when the carboxyl group of the amino acid on the left attacks the amino group of the amino acid on the right. The amino terminal is always to the left. The carboxy-terminal is always to the right. The polarity of each amino acid is due to its R-group. A peptide bond has three features: plantar, restricted mobility, and trans configuration. Restriction enzymes are often utilized in laboratory procedures to sequence-specific proteins. The history of protein sequencing is beyond the scope of this article.[7]

Disulfide Bonds

These are also known as disulfide bridges; these bonds form by nearby cysteine residues within the protein. The cysteine residue has a non-polar R group, more specifically, a sulfhydryl group. This bond is approximately 60 kilocalories per mole of energy. These strong covalent bonds result from chemical interaction associated with proteins that fold in the rough endoplasmic reticulum - this is because reducing agents break disulfide bonds, and the relatively high concentration of reducing agents in the cytosol break sulfur-sulfur bonds as soon as the bonds form. The main reducing agent in the cytosol is a tripeptide called glutathione. The classic Anfinsen's experiment is the basis of this understanding. The experiment utilized ribonuclease, a functional representation of a mature structure with numerous disulfide bonds. The experiment treated ribonuclease with reducing agents that denature the protein, specifically urea, which breaks all weak chemical bonds in the protein. Beta-mercaptoethanol was another reducing agent utilized. The result was a protein with no biological activity because it no longer had an active site. It is said to be a denatured form of the ribonuclease protein. The protein was then placed in water with the denaturing agent and a dialysis tubing. They replaced the external dialysis medium several times to remove as many denaturing molecules as possible. After dialysis, they found that the ribonuclease renatured into 100% functional status, which led to the conclusion that the primary structure determines the tertiary structure.[7] 

Biochemical Reactions 

The most important proteins in the body are those that help with reactions. These are called enzymes, and their main job is to help the body generate energy. Reactions are always possible but not always favorable. Approximately 90% of the reactions that occur in the body would not operate at the appropriate speed required for life. Enzymes, therefore, act as "catalysts." Approximately 80% of reactions in the body would not occur if not for an enzyme being present to catalyze the reaction. Enzymes make reactions more probable by making them easier to occur. They bring substrates together in space and time. Enzymes lower the free energy of activation, which translates to less energy needed for a reaction to occur. Enzymes also stabilize the high energy substrate intermediate within a reaction and are not consumed in the reaction. An enzyme can be classified as globular if it's a highly folded polypeptide that often exhibits a spherical shape and is stabilized by weak chemical interactions.[8]

Sources

Protein is a vital part of the human diet and is present in various foods, like eggs, meats, dairy, seafood legumes, nuts, and seeds. Irrespective of the source of the protein consumed, it gets broken down in reformed into new proteins in our bodies. These proteins do everything from fighting infections to helping cells divide. The L-isomer of each amino acid is usually the more biologically relevant form as compared to the D isomer.

Classification of Amino Acids

While there are hundreds of amino acids in nature, humans use only 20 of them. One way to further classify them is by defining which ones healthy bodies can and cannot make. 

The three classes of proteins are:

  • Non-Essential
  • Conditionally Essential
  • Essential

Non-Essential Amino Acids

There are five amino acids termed non-essential because they can be obtained from foods and also generated within the body.

The non-essential amino acids are:

  • Alanine
  • Asparagine
  • Aspartic acid 
  • Glutamic acid 
  • Serine 

Conditionally-Essential Amino Acids

There are six amino acids termed conditionally-essential because healthy bodies can generate them under normal physiologic conditions. They become essential under certain conditions lIke starvation or inborn errors of metabolism. 

The conditionally essential amino acids are:

  • Arginine
  • Cysteine 
  • Glutamine
  • Glycine
  • Proline
  • Tyrosine

Essential Amino Acids

There are nine amino acids termed essential because they cannot be generated within the body. Dietary protein, therefore, provides these amino acids, which are needed to make certain hormones and other important molecules.

The essential amino acids are:

  • Histidine
  • Isoleucine
  • Leucine
  • Lysine
  • Methionine
  • Phenylalanine
  • Threonine
  • Tryptophan
  • Valine

Development

The four levels of protein structure are: 

  • Primary Structure
  • Secondary Structure
  • Tertiary Structure
  • Quaternary Structure

Primary Structure

Foundationally, a protein is a chain of amino acids bound one to another via peptide bonds. Similar to a string of beads, these strings can twist and fold into a final protein shape. When someone eats protein, it will break down into its amino acids. These amino acids are composed of a central carbon atom bonded to an "amino" or nitrogen-containing group and a carboxylic "acid" group, hence the name "amino acid." The carbon also has a single hydrogen atom and a side chain, or "R-group," which is unique to each amino acid. The exception to this is Proline, which is a ring structure.

Secondary Structure

The secondary structure is the protein structure level at which two common confirmations occur, alpha-helix and beta-pleated sheets. Biologically, this level can further subdivide into three common structures. The third is a combination of alpha-helices and beta-plated sheets, which can form some enzymes.

The first is alpha-helices, which can be present in proteins such as hemoglobin and intermediate filaments. Alpha helixes are amino acids in a coiled or spiral confirmation, allowing hydrogen bonding to form between nitrogen and hydrogen, otherwise known as nitrate groups of one amino acid with the carboxyl group of another amino acid four residues earlier. Some amino acids are more prone to form alpha helixes. Some examples being methionine, glutamine, cysteine, histidine, and lysine.

The second is beta-pleated sheets, which appear in fatty acid transport proteins and antibodies. Beta pleated sheets are amino acids in a series of adjacent rows, allowing for lateral hydrogen bonds to form between the amino acid group with the carboxyl group of another amino acid. When there is a kink in the pattern, it indicates that there is a proline amino acid located at that position. Some amino acids are more prone to form beta-pleated sheets. Some examples being isoleucine, tyrosine, tryptophan, and valine.

Furthermore, there are two biological characteristics of secondary structure—those that are functional and those that are acute phase reactants.

The bone marrow and liver make those classified as functional. The bone marrow produces immunoglobulins. In the liver, albumin, fibrinogen, and alpha-1-antitrypsin are all produced. The liver produces approximately 90% of the proteins that serve as the osmotic gradient within the serum. An osmotic gradient is needed to pull fluid in and out of the capillaries.

The acute phase reactants are those proteins made during inflammation. They are non-specific and used to monitor whether inflammation is occurring in the body. Examples include transferrin and ceruloplasmin.[9]

Tertiary Structure

The most critical factor that contributes to the tertiary structure is its hydrophobic and hydrophilic interactions. The hydrophobic fat-soluble amino acids within a protein will fold towards the protein's "inside" and away from contact with water. In contrast, hydrophilic water-soluble amino acid residues will fold towards a protein's "outside," towards contact with water. Also, tertiary is the level at which covalent bonds form. All of these characteristics contribute to the three-dimensional shape that ultimately forms.[10]

Quaternary Structure

Quaternary structure is the level at which two or more proteins interact with each other and is termed cooperativity.

When cooperativity is applied to the composition of enzymes, it classifies as an allosteric enzyme. And allosteric enzymes are usually rate-limiting enzymes. They are the proteins that control a specific step within a pathway. The rate-limiting enzyme is therefore involved in the step that is termed the" rate-limiting step." If the rate-limiting enzyme becomes slower, then the downstream or subsequent steps also slow down. The vice versa is also true. If the rate-limiting enzyme becomes more efficient, it will increase its speed of a reaction because the downstream steps ultimately occur sooner. So by definition, the rate-limiting enzyme should be the slowest catalyst within the reaction. It also bears mention that most genetic conditions that are clinically significant affect the rate-limiting enzyme of a biochemical reaction. 

The kinetic curve of an enzyme will be shaped in a specific way if the protein is allosteric. The most likely confirmation is sigmoidal, which is significant in first-order elimination. While the pharmacokinetic aspects are beyond the scope of this article, one must appreciate that first-order elimination is associated with substrate concentration and Vmax. When proteins have multiple active sites, their Vmax increases. Proteins are said to be saturated when a substrate occupies all active sites. Clinically this is how protein channels and transporters affect glomerular filtration rate.[11]

Organ Systems Involved

Diet

In general, animal-based protein foods such as eggs, dairy, meat, and seafood provide all nine of the essential amino acids in adequate amounts. Soy-based foods are unique because they are tasteless and provide all nine essential amino in sufficient quantities. Most other plant foods, including whole grains, nuts, legumes, and seeds, possess high levels of some amino acids and low amounts of others. It would be wrong to assume that animal-based foods provide more protein than plant-based ones. A cup of tofu contains the same number of grams of protein as 3 ounces of steak, chicken, or fish. A half-cup of lentils has more grams of protein than an egg. Not all plant foods are low in the same amino acids, so eating a variety of plant-based foods can provide all nine of the essentials. For example, pairing protein sources, like rice and beans or hummus and pita bread or oatmeal topped with almond butter. However, in terms of volume, it may be necessary to eat more plant-based foods to get a similar amount of protein and amino acid profile provided by animal-based proteins.[12]

Digestion

When the food reaches the stomach, hydrochloric acid denatures the protein, unfolding it and making the amino acid chain more accessible to enzymatic action. Then, pepsin, a protein produced by gastric chief cells, cleaves any available protein into smaller oligopeptide chains, which then move on into the duodenum. The second set of digestive enzymes, made by the pancreas, further cleave oligopeptides into tripeptides, dipeptides, and individual amino acids. These products can all be taken up by intestinal cells where dipeptides and tripeptides convert into amino acids. Some amino acids are part of the process of synthesizing intestinal enzymes and new cells. Most enter the bloodstream and are transported to other parts of the body.

Gross Anatomical Manifestation

Hair is a protein that contains a lot of twists and turns. Therefore it is not surprising that hair contains many disulfide bonds Heat denatures proteins; this is why individuals may steam their hair to "relax" and straighten very curly hair. Organ systems in the body possessing beta-pleated sheets require flat tissues such as flat bones and skin.[13]

Function

Proteins serve crucial roles in human biochemistry. The major role is to provide the body's building blocks. They are the precursors of several biologically relevant molecules. Therefore either the excess or deficiency of protein can lead to disease result in nervous system defects, metabolic problems, organ failure, and even death.

Biochemical Functions

Enzymes proteins accelerate a reaction as a catalyst. Catalyzed reactions are one million or more times faster. Enzymes usually have the suffix "-ase" in their name. Exceptions are enzymes discovered before the start of the naming scheme. Each enzyme is regulated by competitive and noncompetitive inhibitors and/or by allosteric molecules. Enzymes can catalyze pathways to produce or break down biological molecules. Changes to enzymes can lead to disease or treatment. Specific amino acids form an enzyme's substrate-binding site. A substrate-binding site is the "active site." This serves in chemical reactions. Substrates can be hydrophobic, hydrophilic, charged, uncharged, neutral, or a combination. Mutations that change amino acids in the active site change the enzyme's activity. A substrate will join an enzyme that is lined with compatible amino acids. If these amino acids change, a substrate may not be able to join, therefore rendering an enzyme non-functional. How a substrate interacts with an active site signifies the "affinity" of that enzyme. Greater affinity means fewer substrate is needed to achieve a reaction. A mutation that changes the active site can raise or lowers the affinity.[14]

Structural Functions

Proteins serve as the structural elements of cells and tissues—the proteins actin and tubulin form actin filaments and microtubules. In muscle, actin provides the "scaffolding" against which myosin can produce muscle contraction.[15]

Kinetic Functions

Motor proteins transport molecules inside a cell, provide movement of certain parts of individual cells involved in specialized function, generate larger-scale movements of fluids and semisolids such as the circulation of blood and movement of food through the digestive tract, and finally provide movement of the human body through their roles in skeletal muscles. Myosin is a protein with a hydrophobic tail, a head group that can attach and detach from actin filaments, and a "hinge" section, which moves the head group back and forth, resulting in movement.[16] 

Channels

Channels are essential for the transportation of nutrients into and out of cells and for nerve signals and the selective filtration of molecules in the kidneys. This is exemplified in how the mammalian cell has an intracellular potassium concentration of approximately 140 millimoles per cell and sodium of 5 to 15 millimoles. The extracellular environment has a potassium concentration of 5 moles and a sodium concentration of 145 millimoles. potassium specific channels are responsible for regulating these concentrations in their respective compartments.[17]

Mechanism

Translation

Protein synthesis is initiated by GTP, which causes ribosomal units to assemble and begin the elongation process, which turns the primary transcript into the amino acid sequence forming the fundamental structure of a protein. Eukaryotic ribosomal subunits are the 40s and 60s, whereas prokaryotic ribosomal subunits are 30s and 50s. The eukaryotic ribosomal subunit is the 80s. The prokaryotic ribosomal subunit is the 70s. The s does not represent the size of the subunits, so, therefore, one must not assume that the total for a subunit complex is the sum of the two individual subunits. The ”s” represents the sedimentation coefficient at which each protein exhibits when subjected to centrifugation. The process of elongation is how the primary structure of a protein is made, which is also known as translocation. A tRNA binds to a specific position termed the site. The TRNA then translocates to the pea site, where it delivers the amino acid to the end of a growing polypeptide chain. Finally, the tRNA moves to the e-site, where it will exit. 

Related Testing

Protein Sequencing

There are several laboratory methods used to determine the characteristics of a protein. These are tests that determine the type, amount, and charge of the amino acids in a protein.

Acid Hydrolysis

  • Used to determine the types of amino acids in a protein.
  • This method can not determine the sequence.
  • Acid hydrolysis is performed by dipping a protein into acid, which denatures the protein.[18]

Gel Electrophoresis 

  • Uses agarose gel to separate proteins primarily by size.
  • It can also separate them by charge if electrodes are added. 
  • Smaller proteins migrate further. 
  • Larger proteins stay closer to the start site.
  • It does not sequence proteins. 
  • There is an electrophoretic pattern for any polypeptide; therefore, gel electrophoresis can be used to detect it.[19]

Ninhydrin Reaction

  • It is a chemical reaction that reacts with an amino acid on the amino-terminal (left). 
  • Reacts with all amino acids creating a purple color. 
  • The proline reaction creates a yellow color. 
  • Used to count the number of prolines in a specific protein.[20]

Edman's Degradation

  • Uses a reagent called phenylisothiocyanate. 
  • Reacts with any amino acid starting on the amino-terminal.
  • Amino acids are identified using thin-layer chromatography or high-performance liquid chromatography.
  • The procedure is accurate only up to 30 amino acids.[21]

Restriction Peptidases

  • Determines a sequence by cutting apart a protein into sets of amino acids.
  • The peptidases are restricted in what they can recognize and cut.
  • Reverse engineering is then used to figure out how they must have been connected.[22]
  • Used to sequence proteins.
  • Have to derive the sequence.
  • Must first know what amino acids the enzymes recognize.
  • Trypsin cuts to the right of LYS and ARG.
  • Chymotrypsin cuts to the right of the aromatic amino acids, PHE, TRP.
  • Elastase cuts to the right of GLY, ALA, SER, the three smallest amino acids.
  • Cyanogen bromide cuts to the right of MET.
  • Aminopeptidase cuts to the right of any amino acid on the amino-terminal.
  • Mercaptoethanol breaks up disulfide bonds.
  • Carboxypeptidase cuts to the left of any amino acid on the carboxyl-terminal.

Pathophysiology

A dysfunctional protein can lead to a variety of medical conditions and, often, death. Dysfunctional proteins can lead to childhood obesity, breakdown of the retina leading to blindness, hearing loss, and type 2 diabetes.

Take, for example, the protein cilia and how its dysfunction manifests.

  • Inadequate cilia in flagella lead to sperm dysmotility.
  • Defective cilia in the respiratory tract lead to chronic lung infections.
  • Eustachian tube cilia dysfunction causes chronic ear infections and hearing loss.
  • Dysfunctional cilia in Fallopian tubes cause infertility.

Infectious

Many infective agents work by mimicking human accessory proteins and binding to elongation factors. Although the bacteria inhibit proteins, viruses actually "hijack" and use the host's protein synthesis machinery for reproduction and further infection. Infectious, misfolded proteins called "prions," short for "proteinaceous and infectious virions," infect as a normally folded protein then replicate and misfold into β-sheets called an "amyloid fold." These aggregate into amyloid plaques and create "holes" in tissue creating a "spongiform" appearance. Prions affect nervous tissue leading to harmful and deadly neurological symptoms.[23]

Cartilaginous

Mutations that alter collagen's structure promote frequent fractures, easy bruising, weak joints, and hearing loss due to abnormal inner ear bones.[24] 

Enzymatic

A genetic disease can cause a deficiency of the enzyme required to convert amino acids into neurotransmitters and skin pigment. The disease does not result from the decrease in amino acid levels, rather from the high concentration of amino acids. This promotes activity in a minor enzymatic pathway producing toxic products. The presence of these products is screened for in the blood as part of standard neonatal testing.  Patients usually express traits of albinism, white-blond hair, pale blue eyes, and an odor from the toxic products in their sweat, urine, skin, and hair. Treatment of this disease is with a diet low in specific amino acids.[25]

Muscular

Diseases in skeletal muscle proteins may cause a rapid breakdown, therefore resulting in the inability to walk.[26]

Osmotic

Misfolded proteins can cause numerous, clinically significant diseases. Most notably is cystic fibrosis, an autosomal recessive disorder due to a defect in the chloride channel CFTR protein, which regulates water, chloride movement, and mucus production. Normally this protein is a channel for chloride to move out of cells to balance the tonicity of salt and water. Sodium is an ion that moves in a counter-current fashion to balance the osmolality between compartments. This is important in glandular tissues that secrete large concentrations of sodium chloride. Mucus plugs, recurrent infections, infertility, and gastrointestinal dysfunction are common manifestations.[27]

Multifactorial

Acute phase reactants caused mostly by IL-6 made by macrophages and also T-helper cells. Too many acute-phase proteins can be deposited anywhere in the body. The non-specific deposition is called amyloidosis. Deposition into the vasculature alters their integrity. Compliance with blood vessel walls will decrease, leading to less distensibility; this makes the blood vessel more likely to rupture if the pressure goes up—a massive intracerebral hemorrhage in a young person with no prior history of hypertension or trauma. Diagnostic confirmation is via congo red stain, which shows a characteristic apple-green birefringence.[28]

Beta-amyloid or tau protein is present in both age-related and Down syndrome-related Alzheimer disease (beta-lipoprotein E4 is more specific for Alzheimer's disease). In the general population, this protein gets oxidized, causing Alzheimer disease. Neurofibrillary tangles are the manifestation of the tau protein undergoing oxidation and aggregating. In Down syndrome, the body is not able to cleave the beta-lipoprotein from the amyloid precursor protein. The result is the build-up of beta lipoprotein, which causes early-onset Alzheimer disease.

Clinical Significance

Signs and Symptoms

  • Malnutrition
    • Dementia
    • Pellagra (The 3 Ds)
      • Depression
      • Dermatitis
      • Diarrhea
    • Mental changes
    • Anorexia
    • Weight loss
    • Glossitis 
  • Encephalopathy
    • Confusion
    • Coma
    • Asterixis
    • Fetor hepaticus [29]
  • Enteropathy
    • Intestinal dysfunction
    • History of organ transplantation
    • Vascular congestion
    • Pitting edema
    • Ascites
    • Alpha 1 anti-trypsin deficiency
    • Recent Tm99 scintigraphy 

Pharmacotherapy

  • Cephalosporins can bind to the penicillin-binding proteins, thereby inhibiting bacterial cell wall synthesis.
  • Macrolides and Lincosamide both bind to the 50s ribosomal subunit, which inhibits bacterial protein synthesis
  • Aminoglycosides and Tetracyclines both bind to the 30s ribosomal subunit, which blocks aminoacyl-tRNA from binding, thus inhibiting bacterial protein synthesis. [30]

Laboratory Medicine

  • Plasma and serum protein concentration is approximately 7.0 g/dl/L
  • CSF protein concentration is approximately 0.48 g/dl/L
  • Urine protein concentration is approximately 1.5 g/day
  • Serum protein concentration is approximately 140 mEq/L
  • Approximately 50% of serum protein is albumin.
    • Hypoalbuminemia is approximately < 2.5 g/dl.
  • Approximately 48% of serum protein is globulin.[31] The composition is as follows:
    • Alpha 1: approximately 5.7%
    • Alpha 2: approximately 9.4%
    • Beta: approximately 11.6%
    • Gamma: approximately 17%

Erythrocyte Sedimentation Rate & C Reactive Protein

If there are too many proteins in the plasma, it can be reflected in laboratory studies by an elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). ESR is a blood test that determines the rate of red blood cell sediment during centrifugation in one hour. CRP is an opsonin that binds to the surface of dead cells to activate the complement system. An elevation in CRP indicates nonspecific inflammation. An elevated ESR does not specify which proteins have increased. Other factors that affect ESR are microcytic anemia, sickle cell anemia, and polycythemia. The value in ESR comes from its ability to show whether an inflammatory or non-inflammatory process.

Envision that there is a vial of a patient's plasma. Shake it up and turn it upside-down. Count how long it takes for one RBC to float down to the bottom. Once it hits the bottom, the clock stops. If it hits the bottom quickly, then the sedimentation rate is low.

If proteins are in the way, the erythrocytes will bounce around until they reach the bottom; this will cause a high sedimentation rate. Anemia will cause a false high sedimentation rate because there are so few cells in the vial; by chance alone, it will take a long time for one to finally float to the bottom.

A falsely low sedimentation rate can occur if the vial is already full of erythrocytes. Therefore it is not necessary to run a rate on a polycythemic patient since the cell count will confound the result. Sickled red blood cell shape allows for the cells to arrive at the bottom of the vial quicker, making the sedimentation rate falsely low.[32]

Preventive Health

Diabetes

High protein diets can promote weight loss via increased insulin sensitivity, increased oxidation of fatty acids, increase, and appetite suppression increased satiety. However, caution is necessary for people with diabetes who have gout because protein can elevate niacin levels, which may exacerbate gout related symptoms.

Screening

Certain protein combinations can be useful in health screenings. For example, certain combinations of proteins have a sensitivity for detecting cancer higher than testing for one particular protein alone.[33]


Article Details

Article Author

Andrew LaPelusa

Article Editor:

Ravi Kaushik

Updated:

11/21/2021 11:02:18 PM

PubMed Link:

Physiology, Proteins

References

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