PRIN401 WEEK 7 BETA

yes, ethanol can be oxidized to aceteldehyde. the acetylaldehyde is then oxidized to acetate and the acetate is converted to acetyl CoA.

hepatocytes can burn the acetyl  CoA to make ATP (used as a fuel) or use it as a substrate to build fatty acids and/or ketones

OCT 16. METABOLISM II. DR. WARREN WILLIAMS

the accumulation of acetaldehyde, acetyl CoA, NADH in the liver

alcohol dehydrogenase

it can also be oxidized to acetaldehyde by a hepatic "microsomal mixed function oxidase", which uses cytochrome P450.

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ethanol can compete for this enzyme and slow the rate at which some drugs are metabolized

acetaldehyde is toxic and can cause the systemic effects

2 factors contribute to this:

1)

beta oxidation of FA is slowed by high NADH/NAD+ ratio, XS FA are converted to TAGs

2)

the liver's ability to export lipids is reduced by alcohol, consequently TAG is stored, leading to a fatty liver.

lactic acidosis + inhibits gluconeogenesis

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high NADH/NAD+ ratio promotes conversion of pyruvate to lactate --> lactic acidosis

also...

it can greatly decrease the hepatocyte's ability to use lactate as a substrate for gluconeogenesis

marasmus is starvation as a result of lack of fuel, aka calorie deficiency

kwashiorkor is starvation due to protein deficiency in the diet, typically found in areas where people have very limited food variety, often eating mostly a single carbohydrate such as maize or rice.

(from `METABOLISM II` p.4)

glycolysis and lactic acid fermentation 

(since RBCs only use anaerobic mechanisms)

(from `METABOLISM II` p.1)

one

(from `METABOLISM II` p5 )

fat, protein

ketones

protein

(from `METABOLISM II` p.5)

it can promote hypoglycemia

under the following conditions:

malnourished (some alcoholics) -- low glycogen stores

children -- low glycogen stores

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no recent dietary intake

alcohol will inhibit gluconeogenesis (ethanol does not inhibit glycogenolysis, so it tends to produce hypoglycemia only in people who have poor glycogen stores)

ethanol is catabolized, producing lots of NADH, which slows CAC.

buildup of acetyl CoA, which make fatty acids, which are stored in liver

+ if hypoglycemic, then increase in lipolysis and FA are taken up by fatty liver

it will inhibit aldehyde dehydrogenase.

with this drug, they are unable to metabolize the acetylaldehyde fast enough and it will accumulate.

the accumulation will cause nausea, vasodilation, etc and deter them from using alcohol

It can be inhibited by HMG CoA reductase inhibitors (aka statins). 

This is because HMG CoA reductase leads to synthesis of cholesterol. 

(from "PHARMACOLOGY OF EICOSANOIDS p.2) 

Drugs that treat Alzheimer's disease are usually Acetylcholinesterase inhibitors. Since Acetylcholine becomes depleted in Alzheimer's , Acetylcholinesterase inhibitors will prevent the breakdown of acetylcholine, thereby increasing acetylcholine levels .

Drugs that treat Parkinson's disease are usually Monoamine Oxidase (MAO) inhibitors. Since Dopamine becomes depleted inParkinson's, MAO inhibitors will prevent the breakdown of dopamine, thereby increasing dopamine levels. 

(from "PHARMACOLOGY OF EICOSANOIDS p.2) 

autocoids

arachidonic

(from "PHARMACOLOGY OF EICOSANOIDS p.3) 

The Arachidonic Acid cascade has 2 fundamental pathways : 

• Lipoxygenase (LO) pathway --> produces Leukotrienes 
• CycloOXygenase (COX) pathway --> produces Prostaglandins (PG), Thromboxane A2 (TxA2), and Prostacyclin (PGI2)

(from "PHARMACOLOGY OF EICOSANOIDS p.3) 

ASA: ASpirin

Ibuprofen: Advil 

Acetaminophen: Tylenol 

ASA and Ibuprofen are NSAIDs. 

(from "PHARMACOLOGY OF EICOSANOIDS p.4) 

antiplatelet

irreversible

(The irreversible inhibition makes ASA a more effective antiplatelet agent than reversible COX inhibitors. 

(from "PHARMACOLOGY OF EICOSANOIDS p.6) 

Epinephrine is produced by cells of the adrenal medulla, and it is a derivative of  tyrosine. It acts on the liver , adipose tissue, and skeletal muscle. It is released when blood glucose levels are low. 

from "ENDOCRINE REGULATION OF METABOLISM p.7" 

• increases glycogenolysis
• increases gluconeogensis
• increases lipolysis
• increases glucagon secretion 
• decreases insulin secretion 

from "ENDOCRINE REGULATION OF METABOLISM p.7" 

Cortisol has Catabolic effects, is produced in the adenal Cortex, and is a derivative of Cholesterol 

It is released during a prolonged fast. 

• increases glucose production 
• increases lipolysis
• decreases glucose utilization

from "ENDOCRINE REGULATION OF METABOLISM p.7-8" 

Growth hormone is produced and secreted from somatotropes (type of cell) of the anterior pituitary. It is released during a prolonged fast. 

• increases glucose production
• increases protein synthesis (growth) 
• decreases glucose utilization (to save glucose for the brain) 

from "ENDOCRINE REGULATION OF METABOLISM p.8" 

stored: ATP + creatine phosphate

carbohydrate

fat

protein

blood lactate

• diabetic retinopathy
• peripheral neuropathy
• kidney failure
• heart disease

from "ENDOCRINE REGULATION OF METABOLISM p.8" 

from pyruvate to acetyl CoA

that turns from aerobic to anaerobic (the krebs cycle and beta oxidation is aerobic)

1. absolute insulin deficiency causes the body to rely on alternative energy sources eg. gluconeogenesis from fats

2. increased lipolysis causes high free Fatty acids, which causes high conc. of ketone bodies

3. the result is ketoacidosis and hyperosmolarity (dehydration ) 

4. These could result in LOC (Loss Of Consciousness) and Death 

from "ENDOCRINE REGULATION OF METABOLISM p.9" 

you will use ATP and creatine-phosphate

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creatone-PO₃² + ADP + H⁺ <--> ATP + creatine

Fat cells are endocrine cells. Fat cells produce and secrete leptin, which signal the hypothalamus (brain part) to decrease food intake and increase energy expenditure. 

from "ENDOCRINE REGULATION OF METABOLISM p.10" 

(this is the last card for this lecture)

(ANSWER)

in the hepatocyte:

glycogenolysis and gluconeogenesis create glucose, which is transported into the blood

in the adicocyte:

TAGs will be broken down and glycerol will go to the liver and FA go to blood stream

in skeletal muscles:

glucose is broken down into pyruvate, which is then broken down into lactate (exported into blood), and then transformed into acetyl-coA

2 pyruvate molecules are made, and 2 ATP molecules are made

harder to get O2 to ETC

and

pyruvate will start to accumulate in the muscles, which turns into lactate in the muscles

1) creatine phosphate reaction

2) glucose --> lactate reaction (anaerobic)

3) fatty acids (at rest: mostly fatty acids; moderate activit: fat + glucose)

first way: as described in the diagram, insulin receptors are activated by insulin binding, the AMPK pathway is activated, thus resulting in visicles with GLUT4 transporters inserted into the sarcolemma

second way: Exercise can trigger insertion of GLUT4 into the sarcolemma independent of AMPK and insulin. It is important to know that this is how skeletal muscles continue to import glucose despite depressed insulin levels during exercise

* sarcolemma is the name of the cell membrane of a muscle cell

from "EXERCISE METABOLISM p. 6" 

(this is the last flash card for this lecture)

morphological (small to big)

histochemical (oxidative to glycolytic)

functional (slow to fast)