Alcohol Treatments
Pentoxifylline lowers blood viscosity and has been shown to decrease hypertension in this important system in the liver which can be affected by alcohol-induced hepatitis and cirrhosis.
What is the hepatic portal system? (Note: treatment with pentoxifylline only leads to modest benefits)
What is insulin?
Cholesterol synthesis, which occurs during the fed state in the cytosol, shares this substrate in common with ketone synthesis, which happens in the fasted state in the mitochondria.
What is HMG-CoA?
Build-up of acetaldehyde can be dangerous because it binds to molecules and forms acetaldehyde adducts. These are recognized as foreign by the body and cause cellular destruction by this cell type, leading to hepatic inflammation and tenderness upon palpation.
What are neutrophils?
Thiamine deficiency is mostly commonly seen in patients with alcoholism. Name two enzymes for which thiamine acts as a cofactor. (Half credit given if only one enzyme named)
What are PDH, aKG Dehydrogenase?
True or false: If a patient has cardiovascular disease, they should be given GLP-1 agonists or SGLT-2 inhibitors for their protective cardiovascular effects.
What is True?
Acetaldehyde is dangerous to cells and is therefore converted to acetate by ALDH in the mitochondria of hepatocytes. The acetate then goes to the bloodstream to be transported to other cells, where it is converted into this molecule to be used to generate energy.
What is acetyl-CoA? (through the enzyme acetyl-CoA synthetase)
A high mitochondrial NADH:NAD+ ratio resulting from excess alcohol consumption slows down PDH in hepatocytes; the cells compensate by doing this (in the cytosol) to allow glycolysis to continue.
What is convert pyruvate into lactate to regenerate NAD+ in the cytosol?
Acamprosate promotes alcohol abstinence in ethanol-dependent patients at the onset of treatment and/or after alcohol detoxification by acting on these neurotransmitter systems in the CNS.
What are glutamate and GABA neurotransmitter systems in the CNS? (also accept calcium channels)
True or false: GLUT2 is paired with glucokinase because they both have low Kms.
What is false? (The pairing is correct, the reasoning is not)
Excessive alcohol consumption leads to increased fatty acid production in the liver, which is then transported out of the liver via VLDLs. Name three proteins required in the synthesis of VLDLs (half credit given for two proteins named)
What are ApoB100, ApoE, ApoCII, and MTTP?
The metabolism of ethanol in the liver leads to the production of reactive oxygen species (ROS) which can damage cells. RBCs are especially susceptible, and therefore contain this antioxidant, a tripeptide which consumes NADPH, to scavenge ROS to protect cells.
What is glutathione?
Ethanol activates this type of receptors (which induces the release of endorphins) that naltrexone acts as an antagonist for.
What are opioid receptors?
Sulfonylureas come with a risk of hypoglycemia because it triggers insulin release by mimicking a rise in the body's blood glucose level without there actually being an increase. Sulfonylureas are able to trigger the insulin release through this mechanism.
What is blocking potassium channels to lead to beta-cell depolarization?
A high NADH: NAD+ ratio in the cytosol due to excess alcohol consumption in the fed state leads to inhibition of G3P dehydrogenase. This results in a clinical symptom also seen in diabetics.
What is hyperglycemia? (G3P dehydrogenase is responsible for the conversion of G3P to 1,3-bisphosphoglycerate; inhibition slows down glycolysis, which in turn leads to slowed clearance of blood glucose levels)
Excess alcohol consumption leads to excess cholesterols synthesis in the liver, which are then esterified to be stored within cells. True or false: This esterification is done by ACAT, not LCAT. (Bonus 200 points awarded if answer can be justified by explaining locations of both enzymes).
What is True? (LCAT is attached to HDLs and in circulation; they esterify cholesterol released by cells so the esterified cholesterol can be incorporated into the HDLs and transported back to the liver or to other lipoproteins)
Prednisolone is the first-line treatment for patients with a Maddrey Score of higher than this number, which indicates poor prognosis.
What is 32? Note: The score is calculated using Discriminant Function = 4.6 * (Pt's PT - Control PT) + TBili
This class of incretins acts by inhibiting the enzyme that degrades GLP-1.
What are DPP-4 inhibitors?
Patients with alcohol addiction may have poor diets, resulting in multiple vitamin deficiencies such as B9 (folate) and B12 (cobalamin). These two vitamins work closely with one another; what is one way to distinguish between a B9 deficiency versus a B12 deficiency?
What is build-up of methylmalonyl-CoA, or neurologic disease? (Note: methylmalonyl-CoA is involved in the b-oxidation of odd-chain FAs)
The high cytosolic NADH:NAD+ ratio generated by excessive alcohol consumption induces FA synthesis and inhibits FA oxidation. Malonyl-CoA, an intermediate in FA synthesis, inhibits FA oxidation through this mechanism.
What is binding to CPT1 to prevent the transport of fatty acyl-CoA into the mitochondrial matrix?