Introduction
All herpes viruses can develop a latent state within specific tissues, in which they rest until reactivation. Reactivation is triggered by menstruation, anxiety states, fever, sunlight exposure, or weakening of the immune system. Viruses cause cells to become multinucleated giant syncytial cells with intranuclear inclusion bodies, and cause local destruction when they migrate to the peripheral skin. Disease is resisted by cell-mediated immunity, but the virus remains latent in nerve cells throughout one's life.
Only alpha subfamily viruses (herpes simplex 1 and 2, and varicella zoster) cause cell damage to the skin.
Herpes simplex virus 1 & 2
Latent in nerve cell bodies. HSV-1 produces most cold sores and HSV-2 produces most genital herpes. Symptoms include watery blisters in the skin or mucous membranes of the mouth, lips or genitals. Herpes simplex can be spread through contact with saliva. HSV infection during pregnancy can result in transplacental viral transfer (by crossing the blood-placenta barrier).
Varicella zoster virus
Latent in nerve cell bodies. Causes varicella (chickenpox) AND herpes zoster (shingles). A breakout of shingles causes painful skin rashes.
Cytomegalovirus
Latent in salivary glands, and dendritic and myeloid cells. CMV infects both epithelial cells and various cells of the immune system. Infection is typically unnoticed in healthy people, but can be life-threatening for the immunocompromised. CMV causes four infectious states: (1) Asymptomatic (2) Congenital disease in infants by transmission from mother, causing mental retardation (3) Mononucleosis syndrome in young adults (4) Reactivation, causing retinitis (blindness), pneumonia or disseminated infection.
Epstein-Barr virus
Latent as multiple copies of circular DNA. Causes mononucleosis by infecting B cells, and is involved in certain cancers. EBV causes cells to "transform" and act as cancer cells, passing on copies of EBV DNA to their progeny. However, malignant cells are cleared by the immune system, with the resolution of mononucleosis illness.
Tuesday, June 10, 2014
Monday, June 9, 2014
Hepatitus Viruses
Introduction
There are five main hepatitis viruses (types A, B, C, D and E) that infect the liver. F and G are not considered to be dangerous. Only hepatitis B (and hepatitis F) viruses are DNA viruses; the remaining types are RNA viruses. All hepatitis viruses are parenteral transmission except for A and E, which are fecal-oral transmission.
Symptoms
Acute (lasting fewer than 6 months)
Initial non-specific flu-like symptoms. May include fatigue, fever, headache, muscle and joint aches, coughing, vomiting, and diarrhea. Many hepatocyte death results in the release of high levels of cell enzymes AST and ALT. Some pericanalicular (bile duct lining) cell death results in low levels of GGT and alkaline phosphatase. The presence of these enzymes in the blood is a sign of hepatitis.
As the liver swells, the bile duct becomes blocked, causing a backup of bilirubin to the blood. In 1-2 weeks, the buildup of bilirubin leads to jaundice due to the liver's failure to metabolize and excrete bilirubin.
Chronic
Often asymptomatic, with enlarged liver and mildly elevated liver enzyme levels in the blood. A first-time, acute hepatitis infection can become chronic if the virus is not cleared in 6 months.
HAV
Frequently affects young children. Transmitted by fecal-oral route from poor hand washing, or from ingesting contaminated water.
HBV
Virus lives in all fluids of an infected patient. Transmitted by blood and sexual contact. Only 10% develop chronic hepatitis.
HCV
Leading cause of chronic hepatitis in the United States. 85% develop chronic hepatitis from acute infections. Transmitted parenterally primarily via injections from drug use.
HDV
Replicates only with the help of HBV by using the envelope of HBV to cause infection. An HDV infection to a chronic HBV carrier results in severe acute hepatitis. As carriers can't make antibodies against HBV, they also become carriers of HDV.
HEV
Similar to HAV. Endemic to Asia, India, Africa, and Central America.
There are five main hepatitis viruses (types A, B, C, D and E) that infect the liver. F and G are not considered to be dangerous. Only hepatitis B (and hepatitis F) viruses are DNA viruses; the remaining types are RNA viruses. All hepatitis viruses are parenteral transmission except for A and E, which are fecal-oral transmission.
Symptoms
Acute (lasting fewer than 6 months)
Initial non-specific flu-like symptoms. May include fatigue, fever, headache, muscle and joint aches, coughing, vomiting, and diarrhea. Many hepatocyte death results in the release of high levels of cell enzymes AST and ALT. Some pericanalicular (bile duct lining) cell death results in low levels of GGT and alkaline phosphatase. The presence of these enzymes in the blood is a sign of hepatitis.
As the liver swells, the bile duct becomes blocked, causing a backup of bilirubin to the blood. In 1-2 weeks, the buildup of bilirubin leads to jaundice due to the liver's failure to metabolize and excrete bilirubin.
Chronic
Often asymptomatic, with enlarged liver and mildly elevated liver enzyme levels in the blood. A first-time, acute hepatitis infection can become chronic if the virus is not cleared in 6 months.
HAV
Frequently affects young children. Transmitted by fecal-oral route from poor hand washing, or from ingesting contaminated water.
HBV
Virus lives in all fluids of an infected patient. Transmitted by blood and sexual contact. Only 10% develop chronic hepatitis.
HCV
Leading cause of chronic hepatitis in the United States. 85% develop chronic hepatitis from acute infections. Transmitted parenterally primarily via injections from drug use.
HDV
Replicates only with the help of HBV by using the envelope of HBV to cause infection. An HDV infection to a chronic HBV carrier results in severe acute hepatitis. As carriers can't make antibodies against HBV, they also become carriers of HDV.
HEV
Similar to HAV. Endemic to Asia, India, Africa, and Central America.
Thursday, June 5, 2014
Influenza Viruses (Orthomyxoviridae and Paramyxoviridae)
StructureViruses are spherical, containing negative stranded RNA; outer membrane contains hemagglutinin activity (HA) and neuraminidase activity (NA) glycoproteins that are anchored to the inner lipid bilayer by M-proteins.
Hemagglutinin
Attachment to host cell sialic acid receptors, which are found on the surface of red blood cells, and upper respiratory tract cells. HA is needed for absorption of the viral genome.
Neuraminidase
Cleaves neuraminic acid of the mucin upper respiratory barrier to expose sialic acid receptors; also cleaves sialic acid receptor to avoid attachment of budding viruses, which will escape to infect new cells.
In paramyxoviruses, HA and NA are part of the same glycoprotein spike. They also contain fusion protein (not found in orthomyxoviruses) that causes the infected cells to fuse into giant multinucleated cells.
Orthomyxoviridae
Orthomyxoviruses are influenza viruses, of which there are three types. Type A infects humans, other mammals, and birds, whereas type B and C infect only humans. Type A causes the most severe disease, with Type B and C in decreasing severity.
Paramyxoviridae (colds/flu in adults, pneumonia in children, measles, mumps)
Paramyxoviruses include parainfluenza viruses, respiratory syncytial virus (RSV), metapneumovirus, mumps virus, and measles virus.
Metapneumovirus causes upper and lower respiratory tract infections primarily in young children or elderly. Parainfluenza and RSV cause upper respiratory infections that have cold-like symptoms in adults, but produce influenza-like sickness from lower respiratory tract infections (bronchiolitis, viral pneumonia, croup) in children, elderly, and immunocompromised patients.
Sunday, March 23, 2014
Amino Acids
Functions
Amino acids have interconnections with other biochemical processes of the body. They can be used for energy (ketogenic), or be converted to glucose (glucogenic). Ketogenic amino acids can convert directly to acetyl CoA, while glucogenic amico acids can convert to intermediate molecules in the Krebs cycle, which can contribute to the synthesis of glucose.
Amino acids also contribute to the formation of nucleic acids, spingolipids, hormones, peptides, and other molecules.
Mnemonics
Essential 10
"Private Tim Hall" (Phe Val Thr Trp Ile Met His Arg Leu Lys).
Purely ketogenic
Only leucine and lysine are not glucogenic.
Both glucogenic and ketogenic
"Tip" ([Thr Tyr Trp] Ile Phe).
The remaining amino acids are purely glucogenic.
Excretion
Excess amino acids are not stored, so they are used as energy or converted into other molecules. In this conversion, the -NH2 groups are removed (by transamination), transported, and excreted as urea:
Amino acids have interconnections with other biochemical processes of the body. They can be used for energy (ketogenic), or be converted to glucose (glucogenic). Ketogenic amino acids can convert directly to acetyl CoA, while glucogenic amico acids can convert to intermediate molecules in the Krebs cycle, which can contribute to the synthesis of glucose.
Amino acids also contribute to the formation of nucleic acids, spingolipids, hormones, peptides, and other molecules.
Mnemonics
Essential 10
"Private Tim Hall" (Phe Val Thr Trp Ile Met His Arg Leu Lys).
Purely ketogenic
Only leucine and lysine are not glucogenic.
Both glucogenic and ketogenic
"Tip" ([Thr Tyr Trp] Ile Phe).
The remaining amino acids are purely glucogenic.
Excretion
Excess amino acids are not stored, so they are used as energy or converted into other molecules. In this conversion, the -NH2 groups are removed (by transamination), transported, and excreted as urea:
- By transamination, 2-ketoglutarate transfers its oxygen to the amino acid while removing and taking on the -NH2 group to form glutamate. (2-ketoglutarate is a Kreb's cycle intermediate, and a nitrogen transporter).
- Glutamate travels to the liver and releases ammonia (oxidative deamination) to the urea cycle. In the process, glutamate changes back to 2-ketoglutarate.
Saturday, March 22, 2014
Lipids
Fatty acid synthesis and oxidation
The synthesis and breakdown of fatty acid chains are due to repetitive cycles that add and remove two carbons each time. Synthesis occurs in the cytosol while oxidation occurs in the mitochondrion. In the breakdown cycle, energy molecules NADH, FADH2 and acetyl CoA are produced, which results in 17 ATPs for each two-carbon loss.
Hormonal controls
When blood sugar is low, epinephrine, norepinephrine and glucagon stimulate lipase in fat cells to break down triglycerides. The glycerol can then be used to produce more glucose.
In contrast, insulin promotes the transport of glucose into cells, where glucose is converted and stored as triglyceride. Insulin also inhibits lipid breakdown through several mechanisms and increases synthesis of glycogen, fatty acids, triglycerides and proteins.
Ketones
In states of starvation, fatty acid breakdown results in the four-carbon acetoacetyl CoA. Acetoacetyl CoA can break down further to acetyl CoA, be used for synthesis of cholesterol, or change to ketones. Ketones may be used for fuel by the brain as a last resort.
Lipids
Fatty acids are stored on the three-carbon glycerol, forming glycerides. Triglycerides are the main storage molecules, which can revert to fatty acids and glycerol - to be used for cellular energy (glycerol to glycerol 3-P to glyceraldehyde 3-P). Acetyl CoA from the energy pathways with glycerol can form triglycerides. Therefore, excess sugar from the diet goes into glycerol to fatty acids (via acetyl CoA) to triglycerides, which are stored in fat cells.
Phosphoglycerides
Glycerol can also form phosphoglycerides when attached to phosphate attached to serine, ethanolamine, choline or inositol. Compared to triglycerides, phosphoglycerides are esters of only two fatty acids, and are important membrane components.
Prostaglandins
Prostaglandins are fatty acids synthesized throughout the body, having hormone-like effects.
Sphingolipids
These molecules contain two fatty acids and a third group linked to the three-carbon serine. They are found in the nervous system.
Cholesterols
Cholesterol is ingested, but also synthesized from acetyl CoA, which transforms to isoprene. Isoprenes are the five-carbon building block forming isoprenoid molecules, or cholesterols. Cholesterol may then become bile acids and salts (mainly produced and exported by the liver), or form various steroid hormones.
The synthesis and breakdown of fatty acid chains are due to repetitive cycles that add and remove two carbons each time. Synthesis occurs in the cytosol while oxidation occurs in the mitochondrion. In the breakdown cycle, energy molecules NADH, FADH2 and acetyl CoA are produced, which results in 17 ATPs for each two-carbon loss.
Hormonal controls
When blood sugar is low, epinephrine, norepinephrine and glucagon stimulate lipase in fat cells to break down triglycerides. The glycerol can then be used to produce more glucose.
In contrast, insulin promotes the transport of glucose into cells, where glucose is converted and stored as triglyceride. Insulin also inhibits lipid breakdown through several mechanisms and increases synthesis of glycogen, fatty acids, triglycerides and proteins.
Ketones
In states of starvation, fatty acid breakdown results in the four-carbon acetoacetyl CoA. Acetoacetyl CoA can break down further to acetyl CoA, be used for synthesis of cholesterol, or change to ketones. Ketones may be used for fuel by the brain as a last resort.
Lipids
Fatty acids are stored on the three-carbon glycerol, forming glycerides. Triglycerides are the main storage molecules, which can revert to fatty acids and glycerol - to be used for cellular energy (glycerol to glycerol 3-P to glyceraldehyde 3-P). Acetyl CoA from the energy pathways with glycerol can form triglycerides. Therefore, excess sugar from the diet goes into glycerol to fatty acids (via acetyl CoA) to triglycerides, which are stored in fat cells.
Phosphoglycerides
Glycerol can also form phosphoglycerides when attached to phosphate attached to serine, ethanolamine, choline or inositol. Compared to triglycerides, phosphoglycerides are esters of only two fatty acids, and are important membrane components.
Prostaglandins
Prostaglandins are fatty acids synthesized throughout the body, having hormone-like effects.
Sphingolipids
These molecules contain two fatty acids and a third group linked to the three-carbon serine. They are found in the nervous system.
Cholesterols
Cholesterol is ingested, but also synthesized from acetyl CoA, which transforms to isoprene. Isoprenes are the five-carbon building block forming isoprenoid molecules, or cholesterols. Cholesterol may then become bile acids and salts (mainly produced and exported by the liver), or form various steroid hormones.
 |
| Steroidogenesis by David Richfield and Mikael Häggström |
Friday, March 21, 2014
Carbohydrates
An energy source
The pentose phosphate pathway, or the hexose monophosphate (HMP) shunt, is a way to produce energy in the form of NADPH from the oxidation of six carbon sugars. It is an alternative to glycolysis, but its primary role is anabolic rather than catabolic: the transformation of sugars with the release of CO2 produces the five carbon ribose, which can be used for DNA and RNA synthesis. Also, if there is a need for NADH, FAD or CoA, ribose can be converted to glyceraldehyde 3-phosphate used in glycolysis.
The PPP is found throughout the body, in fat and liver cells, which use NADPH for fatty acid synthesis and (in liver) for cholesterol synthesis. Red blood cells lacking mitochondria use this pathway as an important source of energy.
Carbohydrate storage / Glycogen breakdown
Steps of glycogen formation:
Enzymes of glycogen breakdown:
Note that glycogen can only be broken down to glucose or glucose 1-P. Unlike glucose, glucose 1-P does not easily cross membranes, so it is preferred by cells in the muscle or liver.
The pentose phosphate pathway, or the hexose monophosphate (HMP) shunt, is a way to produce energy in the form of NADPH from the oxidation of six carbon sugars. It is an alternative to glycolysis, but its primary role is anabolic rather than catabolic: the transformation of sugars with the release of CO2 produces the five carbon ribose, which can be used for DNA and RNA synthesis. Also, if there is a need for NADH, FAD or CoA, ribose can be converted to glyceraldehyde 3-phosphate used in glycolysis.
The PPP is found throughout the body, in fat and liver cells, which use NADPH for fatty acid synthesis and (in liver) for cholesterol synthesis. Red blood cells lacking mitochondria use this pathway as an important source of energy.
Carbohydrate storage / Glycogen breakdown
Steps of glycogen formation:
- Glucose
- Glucose 6-P
- Glucose 1-P
- UDP-glucose (addition of ribose sugar UTP)
- Amylose (unbranched)
- Glycogen (branched)
Enzymes of glycogen breakdown:
- Phosphorylase breaks apart glucose units, but cannot break 1-6 branching. Glucose units are phosphorylated to become glucose 1-P.
- Debranching enzyme breaks down branched residue, producing more glucose 1-P.
- Salivary and pancreatic amylase can break down starch directly to maltose, which can then split to glucose by maltase.
- Lysosomal alpha-glucosidase, found throughout the body, converts glycogen directly to glucose.
Note that glycogen can only be broken down to glucose or glucose 1-P. Unlike glucose, glucose 1-P does not easily cross membranes, so it is preferred by cells in the muscle or liver.
Thursday, March 20, 2014
Cellular Energy
Energy molecules
ATP is the body's main energy molecule. Energy is stored in forms of glycogen or triglyceride, which can be broken down to regenerate ATP. Some high-energy molecules include:
A note about enzymatic biochemistry reactions
Enzymes and substrates of a reverse reaction are usually found in a different area of the body, so forward and reverse reactions do not compete. If a two-way reaction is found in the same area, then negative (or positive) feedback of enzymes prevent a "futile cycle" (competition within two-way reactions).
ATP production
Glycolysis occurs in all organ cells, producing two pyruvates per glucose. Pyruvate is converted to acetyl CoA, which can enter the Krebs cycle. Besides glycolysis, acetyl CoA can also be formed through fatty acid degradation or by transformation of certain amino acids.
Glycolysis (cytosol)
Produces 2 pyruvate, net 2 ATP and 2 NADH per glucose.
Anaerobic glycolysis (cytosol)
The Krebs cycle needs O2 to run, otherwise anaerobic glycolysis will occur. It is like glycolysis with an extra step: cycle the 2 NADH to replenish 2 NAD+ via transformation of 2 pyruvate to 2 lactate. Net 2 ATP.
Pyruvate decarboxylation (mitochondria)
Produces 2 acetyl CoA and 2 NADH per glucose.
Krebs cycle and Oxidative phosphorylation (mitochondria)
Including pyruvate decarboxylation, the Krebs cycle produces 1 ATP, 1 GTP, 8 NADH, and 2 FADH2 per glucose. In the electron transport chain, phosphorylation (ATP production) is coupled with oxidation (requiring O2 at the end).
Based on newer sources, 2.5 ATP are generated per NADH in the mitochondria. 1.5 ATP are generated per NADH in the cytosol, and per FADH2. This is a total of 30-32 ATP per glucose in aerobic respiration.
Note that the presence of ADP stimulates oxidation, and the lack of ADP (and abundance of ATP) slows the rate of oxidation.
Connections to other processes
Glyceraldehyde 3-P (halves of glucose) can be directed back towards gluconeogenesis, or towards acetyl CoA and the Krebs cycle. Amino acids can be transformed into acetyl CoA or other molecules in the Krebs cycle, and vice versa. Acetyl CoA is also used to generate lipids (lipogenesis). Succinyl CoA can be used to produce heme molecules, while other molecules from the Krebs cycle can be used to make purines and pyrimidines for DNA synthesis.
ATP is the body's main energy molecule. Energy is stored in forms of glycogen or triglyceride, which can be broken down to regenerate ATP. Some high-energy molecules include:
- ATP, UTP, GTP: donators of phosphoryl group.
- NADH, FADH2: donators of electrons or hydrogen.
- Biotin: donator of carboxyl group.
- Acetyl CoA: donator of acyl group.
- Others: THF-C, Thpp, S-Adenosylmethionine, UDP-Glucose.
A note about enzymatic biochemistry reactions
Enzymes and substrates of a reverse reaction are usually found in a different area of the body, so forward and reverse reactions do not compete. If a two-way reaction is found in the same area, then negative (or positive) feedback of enzymes prevent a "futile cycle" (competition within two-way reactions).
ATP production
Glycolysis occurs in all organ cells, producing two pyruvates per glucose. Pyruvate is converted to acetyl CoA, which can enter the Krebs cycle. Besides glycolysis, acetyl CoA can also be formed through fatty acid degradation or by transformation of certain amino acids.
Glycolysis (cytosol)
Produces 2 pyruvate, net 2 ATP and 2 NADH per glucose.
Anaerobic glycolysis (cytosol)
The Krebs cycle needs O2 to run, otherwise anaerobic glycolysis will occur. It is like glycolysis with an extra step: cycle the 2 NADH to replenish 2 NAD+ via transformation of 2 pyruvate to 2 lactate. Net 2 ATP.
Pyruvate decarboxylation (mitochondria)
Produces 2 acetyl CoA and 2 NADH per glucose.
Krebs cycle and Oxidative phosphorylation (mitochondria)
Including pyruvate decarboxylation, the Krebs cycle produces 1 ATP, 1 GTP, 8 NADH, and 2 FADH2 per glucose. In the electron transport chain, phosphorylation (ATP production) is coupled with oxidation (requiring O2 at the end).
Based on newer sources, 2.5 ATP are generated per NADH in the mitochondria. 1.5 ATP are generated per NADH in the cytosol, and per FADH2. This is a total of 30-32 ATP per glucose in aerobic respiration.
Note that the presence of ADP stimulates oxidation, and the lack of ADP (and abundance of ATP) slows the rate of oxidation.
 |
| Cell Respiration by RegisFrey |
Connections to other processes
Glyceraldehyde 3-P (halves of glucose) can be directed back towards gluconeogenesis, or towards acetyl CoA and the Krebs cycle. Amino acids can be transformed into acetyl CoA or other molecules in the Krebs cycle, and vice versa. Acetyl CoA is also used to generate lipids (lipogenesis). Succinyl CoA can be used to produce heme molecules, while other molecules from the Krebs cycle can be used to make purines and pyrimidines for DNA synthesis.
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