L12 Biochemistry of Myopathy Flashcards
Myopathy:
Muscular pain or dysfunction
There are 3 subtypes of skeletal muscle tissue:
Type I: Slow contraction
Type IIa: Medium contraction
Type III b: Fast contraction
Body types in general to proportion of the 3 skeletal muscle types:
Type I:
Type II:
Type III:
Ectomorph
Mesomorph
Endomorph
What are the major molecules for muscular force?
ATP/ ADP Actin Myosin Troponin Tropomyosin Ca++
Sarcolemma
Membrane fiber
Sarcoplasmic Reticulum
Stores Ca++ for flooding the myofibrils- a trabecula of vessels
Myofibrils
Strands of sarcomeres
Sarcoplasm
Cytoplasm of the giant fiber cells
Sarcomere
Muscular contraction unit- primarily actin, myosin, tropomyosin, troponin
Z line
Stiff protein that organizes and links sarcomeres
Actin/ Myosin/ Tropomyosin
Major proteins of sarcomere’s filament bundles- two types: thick and thin
Troponin
A protein attached to actin which regulates Ca++
Cross bridge and head
Part of myosin protein that does the movement work of muscle tissue; uses ATP
Simplified Process of Muscle Contraction
- The motor neuron sends a signal to the muscle fiber to contract.
- Calcium in the sarcoplasmic reticulum floods into the sarcoplasm
- Ca++ attaches to troponin, allowing myosin to attach to actin, myosin breaks the ATP bond, fuelling it’s movements
- Myosin, in attaching to actin, bends at the cross bridge, shoving actin, and contracting the sarcomere unit.
- Ca++ is withdrawn, ATP enters myosin head active site causing myosin to release from actin
- Repeat step 3-4-5 until the sarcomere can’t contract further
- The ____ neuron sends a signal to the muscle to contract.
motor; fiber
- ____ in the sarcoplasmic _____ floods into the sarcoplasm
Calcium; reticulum
- Ca++ attaches to _____ , allowing myosin to attach to _____, myosin breaks the ATP bond, fuelling it’s movements
troponin; actin
- ______, in attaching to actin, bends at the cross bridge, shoving actin, and contracting the _____ unit.
Myosine
sarcomere
- ______ is withdrawn, ATP enters myosin head active site causing myosin to release from ____
Ca++; actin
- Repeat step 3-4-5 until the ______ can’t contract further
sarcomere
____ calcium flux into the sarcoplasm will increase contraction
Increasing
_____ _____ of calcium out of the sarcoplasm allows ______ of the muscle by countermovement
Active transport
relaxation
The stagnation of flow in or out of the _______, whether of Ca++ or nutrients, can keep a muscle fiber contracted
sarcoplasm
The inability of to release usually does not affect an entire muscle, hence the formation of “______” in the muscle
knots
When in a state of excess or repletion, ___ ___ therapy is done using strong ____ needle technique
trigger point therapy
reducing
In treating exhausted muscles that are deficient and contracted, a ___ needling into the tissue stimulates the flow of Qi and Blood to the muscle; Distal ____ or application of tonifiing oil to the local tissue is used
gentle; tonification
If there is a problem with a biochemical pathway, a drug could possibly interfere or change that pathway to _____ it better or ___ it
operate; inhibit
The signature of the plant (color, taste, part used, character) radiates the medicinal action of the plant
Doctrine of Signatures
Supplements or ____ are a substances that are mostly naturally-derived
nutriceuticals
many drugs are derived from ___ and other simpler forms of life like ___ and its derivatives
bacteria; penicillin
Gan Cao
Glycyrrhizin- Liquorice Root
Used in Asia pharmaceutically as antiviral to hepatitis, herpes, HIV; Strong anti-inflammatory properties, protect liver from toxicity, mild laxative (aperient) ; in TCM a Qi Tonic
Glycyrrhizin (Gan Cao) - Liquorice Root
Glycyrrhizin has one notable side effect:
Causes a false condition to develop aldosteronism where potassium/sodium balance in bloodstream is changed, creating HBP. The glycyrrhizin molecule can mildy mimic aldosterone, a corticosteroid produced by the adrenal glands. Aldosterone gets KD to excrete more potassium K+ than normal. Imbalance btw K+/Na+ causes the BP to rise and stay elevated- NA+ in the blood brings in more water to the blood
NSAIDs:
Non- Steroidal Anti-inflammatory Drugs
What are the main uses of NSAIDs?
anti-pyrrhetic (brings down fever)
Anodyne (pain relief)
Anti-inflammatory
NSAIDs inhibit the cyclooxygenase enzymes (COX) that make ____. When cyclooxygenase is inhibited, the lack of ___ keeps the body from creating an inflammatory response to pain, this is felt as relief
prostaglandin; prostaglandin
There are 2 classes of cyclooxygenase,I and II. NSAIDS generally inhibit both types. COX-II drugs are inhibited because they increase
heart attack risk
Common NSAIDS are:
Aspirin, Ibuprofin, Naproxen, Celecoxib
NSAIDS side effect:
When inhibits COX I and II in the ST, chief cells are signaled to keep making HCl, and the pH of ST is more acidic than normal homeostasis => stresses pancreas b/c it has to pump out more bicarbonate to neutralize acid => weakens intestines and create leaky gut syndrome where tight seals between intestinal cells are loosened and undigested food leak into interstitial space=> pt becomes malnourished, gains weight, chronic fatigue, qi xu and damp toxin accumulation
Statin drugs are designed to:
Lower Serum Cholesterol
Fear factor that high serum cholesterol leads to arterial plaque formation which leads to
heart attack and stroke
Stains lower cholesterol by:
Inhibiting the enzyme HMG-CoA reductase, which is the rate-limiting enzyme of the mevalonate pathway of cholesterol synthesis. Inhibition of this enzyme in the liver results in decreased cholesterol synthesis which causes increased synthesis of LDL receptors, resulting in an increased clearance of low- density lipoprotein (LDL) from the bloodstream. The first results can be seen after one week of use and the effect is maximal after four to six weeks.
Side Effects of Statins:
Muscle symptoms are a common side effect of statins; many
people experience aching in the shoulders, pain in the jaw, or muscle pain in the legs. The muscle pain is a symptom muscle breakdown that is occurring in the body due to the side effect of the statin drug. This sometimes leads to a serious myopathic condition called rhabdomyolysis, where skeletal muscle spontaneously breaks down without warning, and if not stopped, will overload the kidneys with breakdown toxins causing kidney failure and death. No mechanism has yet to be demonstrated. Statins inhibit cellular production of ubiquinone, a major molecule in the electron transport chain, used in making ATP. This molecule is particularly important in heart muscle, and may indicate why long-term statin users have a higher rate of heart attacks.
Other side effects include minor to major amnesia — 2% and peripheral neuropathy – 10%. They are also implicated in inducing Type II diabetes.
NAC, or N-acetylcysteine, is an acetylated (add 2 carbons) form of the amino acid cysteine. Western science knows it as a mucolytic, as it helps break up mucus and gets it to flow in the lungs and sinuses. Thus, it is used in cystic fibrosis to loosen the constant phlegm produced in that disease. But it is the mechanism of its action which is most interesting.
On its own, NAC is a useful antioxidant, because of the sulfhydryl group. It has poor absorption in the gut, so large doses are necessary in emergency situations — such as in acetominophen poisoning.
NAC promotes intracellular glutathione production. When
a cell is overwhelmed by oxidative stress, glutathione levels
are taxed, allowing an inflammatory state to get out of
control in the cell. NAC provides the rate-limiting amino acid
cysteine, one of the three amino precursors of glutathione.
Because the precursor cysteine is available, more glutathione can be manufactured, and this enables cells to function optimally. This is important in the lungs during a lung heat condition where phlegm and heat can create an environment perfect for pneumonia development.
NAC is also widely used for treatment of acetaminophen poisoning (paracetamol, or Tylenol). When degraded by hepatocytes, the acetaminophen metabolite is a liver toxin, and if not treated promptly, can severely damage the liver. NAC again promotes the synthesis of glutathione which eliminates the toxic metabolite from the hepatocytes. Other investigational uses of NAC all have to do with its ability to boost glutathione. These are some fields NAC therapy is being studied: nephrotoxicity, schizophrenia, bipolar disorder, obsessive-compulsive disorder, cocaine withdrawal, HIV/AIDS therapeutics and treatment of noise- induced hearing loss.
L-Carnitine is another essential molecule involved in energy generation at the level of the mitochondrion. Earlier, we mentioned that acetyl coenzyme A (ACA) is transported into the mitochondrion from the cytoplasm for use in the Krebs cycle. L-carnitine is the coenzyme that moves the acetyl group of ACA across the mitochondrial outer membrane, through the intermembrane space, and into the matrix of the mitochondrion. This is a slightly complex process with the carnitine recycled by the enzymes involved from carnitine to acyl-carnitine back to carnitine.
It is manufactured from lysine and methionine, and is found in many plant foods. It has antioxidant properties, and is especially protective of lipid bilayer membranes to retard lipid peroxidation.
