Diseases, Drugs, Targets so far Flashcards

Question

What is type 1 diabetes?

Answer 1

Pancreatic beta cells, which produce insulin, are destroyed by the immune system. Without insulin the body loses its ability to fluctuate metabolic activity in response to meals. Beyond being unable to break down glucose, cells involved with high levels of activity (muscle cells) are limited in their ability to pull glucose from the body. GLUT 4, the glucose transport muscle cells use, can be positively regulated by insulin to accept more glucose

Answer 2

Leigh disease is a metabolic disease where the patient's pyruvate dehydrogenase complex enzyme is hindered. This means the body cannot readily take pyruvate and turn it into acetyl CoA for use in the TCA cycle. Instead, pyruvate is shunted into lactate. Lactate is acidic, so this can harm the body. In addition, lacking access to the TCA cycle means the body is constantly deficient of energy. Common symptoms include acidosis (tissue damage), muscle weakness, damage to the brain stem and other "lower order" parts of the brain (cerebellum, basal ganglia)

Answer 3

The body would lose access to ATP, and a lot of key reactions wouldn't be able to take place. Muscle/motor impairment, decreased cell viability, tissue death. Rotenone (fish poison) and amytal (barbiturate sedative) block NADH --> NAD+ oxidation, which cuts out tons of energy from the body. Antimycin A blocks electron flow through cytochrome b-c1 (complex 3) (an electron transport component), which means we lose all but complex 1's H+ output. Cyanide, azide, and carbon monoxide block electron flow through cytochrome C oxidase (complex 4), losing 4H+. Oligomycin stops ATP synthase from working. This is probably the worst, because there's absolutely no way to get around ATP synthase. No ATP synthase = no energy. DNP stops proton gradient

Answer 4

ATP synthase would only be able to use the natural H+ gradient between the intermembrane space (higher initially) and the inner membrane matrix (lower initially). DNP is a known herbicide that acts as a hydrogen ion transport facilitator across the membrane. So it takes the H+ along the concentration gradient, except no ATP is produced. Electron transport chain can work great, but DNP counteracts and ATP synthase doesn't get any H+ to work with.

Answer 5

The mitochondria is the source of basically everything to do with energy production in the cell. If you inhibit some enzyme in the TCA cycle you lose energy. If you inhibit some part of the electron transport chain you lose energy. If you inhibit ATP synthase you can't produce any energy (lethal). In all of these, nervous system damage and muscle weakness are common. Mitochondrial diseases can only be inherited from the mother, because the mitochondrial genome comes straight from her. It may be a small mutation for her but would be amplified in her offspring. Mitochondria produce their own ribosomes, tRNA, complex 1,3 & 4, and atp synthase.

Answer 6

Acyl triglyceride lipase is used to degrade triacylglycerides into glycerol and three fatty acids through addition of water. Without ATGL function you're not able to expose fatty acids. You can't degrade triacylglycerides for energy, so you'll be deficient in energy. You'll also have huge reservoirs of fat. A genetic condition that causes this is called Chanon-Dorfman Syndrome. It leads to muscle weakness, an enlarged liver, and overheating (a lot of energy wasted as heat instead of ATP?)

Answer 7

In type 1 diabetes you're unable to make insulin. What happens? Your body can't digest glucose, so you're low on energy. Glucose is a key reactant for the formation of oxaloacetate. Without OAA you're unable to go through TCA or create aspartate for the Urea cycle, or unable to help with fatty acid synthesis (OAA is used to transport acetyl CoA out of the mitochondria for use by the body). The energy deficit induces the production of ketone bodies as energy storage units. Ketone bodies are acidic, so having high concentrations of ketone bodies in the body leads to tissue damage and enzyme dysfunction. Most notable in the nervous system.

Answer 8

Fatty acids are common precursors for signaling molecules. Tumor cells need a lot of signaling molecules to interact with the environment and acquire more resources from the ECM. Fatty acid synthesis is boosted in cancer. Acetyl CoA carboxylase and beta-ketoacyl ACP synthase enzymes are both overactive. Acetyl CoA carboxylase facilitates the committed step in fatty acid synthesis (malonyl coa from acetyl coa). Beta-ketoacyl ACP synthase catalyzes the elongation of fatty acids (malonyl coa attacks acetyl coa, acetyl coa is added to malonyl coa). Tumor therapies that target these enzymes can lead to apoptosis (cancer cells are often overdependent on their mutations)

Answer 9

Without glycogen you'd have decreased energy storage capacity, but more importantly (since glycogen doesn't account for much of our total energy needs/storage) you lose rapid energy sources (glycogen breakdown is much faster than fatty acid breakdown or ketone body use). What if you can make glycogen but can't use it? You'd have huge buildup of glycogen in the liver and the muscles. If you couldn't move the glycogen to the muscles your liver would get stuffed. Tired, hyperglycemia (because you can't do stuff with the glucose so it just sits in the blood). This is called Von Gerke disease. It's a defect in glucose 6 phosphatase, which is used to turn g6p (from gluconeogenesis and glycogen breakdown) into glucose. You also have glycogen storage disease type III (defect in branching enzyme) means you aren't able to breakdown glycogen as quickly, so you're often tired.

Answer 10

Alcohol digestion requires NAD+ (reduces it to NADH). This changed ratio (NADH/NAD+) decreases fatty acid oxidation (fatty acid oxidation wants to generate energy, but alcohol digestion creates NADH so you don't need to breakdown fatty acids). It also uses up NADPH, which is needed for fatty acid synthesis and amino acid synthesis. Fatty acids accumulate in the liver. Acetyl CoA is shifted towards ketone body production (because NADH presence inactivates pyruvate dehydrogenase complex for TCA). This causes ketoacidosis. High levels of NADH also push equilibrium of pyruvate --> lactate towards lactate (to regenerate NAD+). This causes lactic acidosis (also bad, can cause gout)

Answer 11

Alcohol digestion ramps up presence of NADH. Any pathway that uses or is regulated by NAD+ or NADH will be affected.

Answer 12

Homocystinuria means you have less cysteine than you should. Caused by a defect in cystathionine synthase (takes homocysteine + serine --> cystathionine). You're not able to clear homocysteine and methionine (steps in production of cysteine. methionine turns into homocysteine. homocysteine reacts with serine to become cystathionine. cystathionine gives off an ammonia group to become cysteine), so the concentrations of homocysteine and methionine are abnormally high. Homocysteine is toxic to the body. Leads to intellectual disability, eye trouble, thrombi (blood clots).

Answer 13

Having too much homocysteine (caused by multiple mutations in the homocysteine --> methionine pathway. could be defective FH4, lack of vitamin B12, or defective cystathionine synthase (other direction, turning homocysteine into cystathionine)) leads to cardiovascular and central nervous system damage/disease. Fatal to fetus. Pregnant women take folate supplements to make sure this isn't an issue.

Answer 14

Tyrosine, Acetoacetate, and fumarate are all byproducts of phenylalanine degradation. Disruption in this pathway can decrease the body's ability to make any of these products. Tyrosinemia 1 is caused by a defect in furarylacetoacetate hydrolase which is one of the enzymes taking you from homogentisate to acetoacetate and fumarate. This leads to liver failure, death, and "cabbage-smelling' breath. Tyrosinemia 2 is a defect in tyrosine aminotransferase (takes you from tyrosine to p-hydroxyphenylpyruvate). Leads to eye, skin, and brain troubles. Alkaptonuria - defect in homogentisate oxidase. Homogentisate accumulates, causes joint pain and dark pee. Phenylketonuria - defect in phenylalanine hydroxylase. Phenylalanine concentrations are too high. Tyrosine is an important precursor, and can't be made since phenylalanine hydroxylase is the first step in the process. This leads to severe mental disability unless put on a low phenylalanine diet with tyrosine supplements. Brain damage could be caused by lack of dopamine (formed out of tyrosine)

Answer 15

Branched chain dehydrogenase enzyme (for breakdown of valine, isoleucine, and leucine) is defunct. alpha-ketoacids are formed but can't be broken down. Urine smells like maple syrup. If you don't have a low valine/isoleucine/leucine diet you'll have serious mental and physical disability.

Answer 16

A lack of melanin (formed from tyrosine) due to defunct tyrosinase enzyme. Your skin is white, your eyes are red because the blood vessels are visible. The eye is super sensitive to light because nothing is blocking the rays.

Answer 17

``` Having too much ammonia in your system (which is toxic). Some disorders that cause hypoerammonemia can be countered by supplementing the diet with urea cycle intermediates. Others (defects in early steps of the urea cycle) can't be fixed, but only managed by finding alternative ways to get rid of ammonia. Arginosuccinase is the enzyme that takes you from arginosuccinate to arginine (lose fumarate). If this enzyme is defunct you can add arginine and limit other protein intake. Arginine loses its nitrogens as urea, is used up as ornithine to bind to free ammonia groups, and then is discarded as arginosuccinate. Ornithine transcarbamoylase (takes you from ornithine + carbamoyl phosphate --> citrulline) deficiency prevents ammonia from entering the urea cycle. Carbamoyl phosphate synthetase (takes you from co2 + nh4 --> carbamoyl phosphate) deficiency prevents ammonia from entering urea cycle as well. These have to be solved by finding other ways to get rid of ammonia. One way is to use benzoate and phenylacetate (these remove glycine and glutamine from the system. glycine and glutamine have nh4 groups so removing them decreases nh4+ concentration in the body. ```

Diseases, Drugs, Targets so far Flashcards

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