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Biochem- Ethanol-> Regulation of Metabolism
Corso Lectures Part 1- Biochem Final
111
Biochemistry
Professional
12/10/2011

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Term
What characterizes an amphipathic molecule?
Definition
both hydrophobic and hydrophilic characteristics
Term
What causes portal hypertension in the cirrhotic liver and what is the result?
Definition
Decreased perfusion; esophageal varicies
Term
How many Kcal/gram of alcohol?
Definition
7 Kcal/gram
Term
What vitamins does alcohol consumption limit the absorption of?
Definition
Thiamine, B12, and folic acid
(among others)
Term
What is the function of Alcohol Dehydrogenase (ADH)?
Definition
To convert ethanol to Acetaldehyde
GAIN ONE NADH
Term
What is the function of Aldehyde Dehydrogenase (ALDH)?
Definition
To convert acetaldehyde to Acetate
GAIN ONE NADH
Term
What is the function of Acetyl CoA Synthetase (ACS)?
Definition
Convert acetate to Acetyl CoA
Term
Where does the action of ADH take place?
Definition
Cytosol
Term
Where does the action of ALDH take place?
Definition
Mitochondria
Term
What are the effects of the excess NADH produced in ethanol metabolism?
Definition
Increased lactate and ketone bodies;
decreased fatty acid oxidation and gluconeogenesis
Term
What is another role of ALDH?
Definition
To release the NO from nitroglycerin (relieve the pain of angina)
Term
What happens to Acetyl CoA that results from ethanol metabolism?
Definition
It is mostly oxidized via the citric acid cycle
Term
What is MEOS?
Definition
An alternative pathway for alcohol metabolism that usually only activates at high or constant ethanol levels; DOES NOT GENERATE NADH, but does generate reactive oxygen species
CONVERTS ETHANOL TO ACETALDEHYDE
Term
What is the important function part of the MEOS system?
Definition
Cytochrome P450 enzyme called CYP2E1
This uses NADPH and molecular oxygen to oxidize ethanol
Term
What else is metabolized by the CYP2E1?
Definition
Tylenol
Term
In chronic alcoholism, what is the sole mediator of increased alcohol metabolism?
Definition
The MEOS System
Term
What is the main consequence of inducing the MEOS system?
Definition
Increased amounts of Toxic ACETALDEHYDE
Term
What effect does alcoholism have on the metabolism of drugs that use the MEOS system for breakdown?
Definition
Higher dose of drugs for effectiveness
BUT
If ethanol is consumed while taking the drug, alcohol competes for the enzyme and a lower dose of the drug may be effective
Term
What effect does chronic alcoholism have on levels of MEOS?
Definition
INCREASE
Term
How many ATP are generated by the conversion of ethanol to acetaldehyde by ADH?
Definition
as many as 15 (because of Citric Acid Cycle)
Term
What are the 3 chemical structures responsible for the toxic effects of ethanol metabolism?
Definition
1) Increased NADH: NAD+ ratio
2) Acetaldehyde (toxic)
3) Increased free radical production
Term
What are the acute metabolic effects of alcohol on the liver?
Definition
Excess TGs, hyperlipidemia, fatty liver, increased ketone bodies because TCA cycle is inhibited, ketosis
Term
What are the effects of alcohol on blood sugar?
Definition
Fasting hypoglycemia
Hyperglycemia following a meal
Term
Why does alcohol metabolism cause an increase in TGs?
Definition
High NADH inhibits beta oxidation of fatty acids, so there are too many in the liver and they get converted to TGs
Term
Why does alcohol metabolism cause ketosis?
Definition
High NADH causes OAA to reduce to malate so that citrate cannot be made- as a result, Acetyl CoA cannot enter the TCA cycle, and excess AcetylCoA makes KETONE BODIES
Term
What are two effects of high levels of NADH from alcohol metabolism on blod sugar?
Definition
Inhibits gluconeogenesis (hypoglycemia during fasting)
Inhibits glycolysis
(hyperglycemia in fed state)
Term
What why does alcohol metabolism cause hyperuricemia?
Definition
Excess lactated inhibits uric acid excretion: patients with gout should avoid alcohol
Term
Why does alcohol metabolism cause fatty liver disease?
Definition
Ethanol oxidation replaces fat as a fuel so it accumulates in the liver
Term
Why does acetaldehyde cause free radical damage?
Definition
First, more free radicals are formed by acetaldehyde-adducts
Second, acetaldehyde binds glutathione and lowers its ability to protect against ROS
Term
What leads to decreased serum protein production in alcohol-induced hepatitis?
Definition
Tubulin modification by acetaldehyde- decreased albumin, transferrin, and clotting factors
Term
What is hepato-encephalopathy?
Definition
Liver cannot detoxify so that toxins affect the brain
Alcohol also decreases absorption of vitamins (thiamine) affecting glucose metabolism in the brain and heart
Term
What is Wernicke-Korsakoff Syndrome?
Definition
Altered mental status- the result of alcohol-induced decreased glucose metabolism in the brain (vitamin deficiency)
Term
What causes fibrosis in alcohol-induced liver disease and what initiates it?
Definition
Stimulation of mitogenic development of stellate cells into myofibroblasts;
Macrophages are activated by acetaldehyde-adducts and ROS
Term
What effect does excessive alcohol consumption have on Citric Acid Cycle activity?
Definition
DECREASES
Term
What causes impaired judgment and psychoses in a chronic alcoholic?
Definition
Thiamine Deficiency
Term
What is deficient if laboratory studies show a decrease in transketolase activity of RBCs?
Definition
Thiamine Deficiency
Term
What is "wet Beri Beri"?
Definition
Congestive heart failure due to thiamine deficiency- HIGH OUTPUT heart failure- wet= fluid retention
ADMINISTER THIAMINE
Term
What hormone stimulates fatty acid synthesis in the liver?
Definition
Insulin
Term
What hormone stimulates gluconeogenesis in the liver?
Definition
Glucagon
Term
What bond, found in cellulose, cannot be broken down by us humans?
Definition
Beta 1,4 glucose bond
Term
What bond is broken by amylase?
Definition
Alpha 1,4 glycosidic bonds
Term
Where are sucrase and maltase found?
Definition
On the surface of the intestinal lumen
Term
What sugars are absorbed without digestion?
Definition
Fructose, ribose, and glycerol
Term
What are the products of starch digestion by amylase in the mouth?
Definition
Maltose and limit dextrins
Term
What is a dextrin?
Definition
A shorter polysaccharide chain made by the breakdown of a larger molecule (STARCH)
Term
What are the two monosachharides of table sugar (sucrose)?
Definition
Glucose and Fructose
Term
In lactose intolerance, lactose cannot be broken down into what two sugars?
Definition
Glucose and Galactose
Term
Besides salivary amylase, where does the other amylase get secreted?
Definition
Pancreas- pancreatic amylase
Term
What type of bonds hold together the monosaccharides of amylose (starches)?
Definition
Glucose Alpha 1-4 Glucose- This bond is broken by amylase
Term
What bond holds together the monosaccharides of sucrose?
Definition
Glucose Alpha 1- Beta 2 Fructose
Term
What bond holds together the monosaccharides of lactose?
Definition
Galactose Beta 1-4 Glucose
Term
What is the action of the glucoamylase complex in the small intestine?
Definition
Cleavage of Alpha1-4 linkages
DEGRADES MALTOSE AND MALTOTRIOSE
Term
What is the action of the Sucrase-Isomaltase Complex?
Definition
Digestion of SUCROSE and maltose
Term
What is the function of trehalase, and where can you find the sugar that it acts on?
Definition
Cleaves Trehalose Glucose Alph1,1 Glucose
Mushrooms, honey, and shrimp
Term
What class of enzyme is lactase and what bond does it break?
Definition
Beta Glycosidase; Galactose Beta1,4 Glucose bonds
Term
What ethnic minority has a genetic Trehalase deficiency?
Definition
Greenland Eskimos
Term
What did the Dalai Lama say to the hot dog vendor?
Definition
"Make me one with everything"
Term
What causes lactose intolerance?
Definition
Lactase deficiency from injury to intestinal mucosal cells; gastroenteritis; excess alcohol consumption
Term
What happens to lactose in the absence of lactase?
Definition
Bacterial fermentation= bloating, flatulence, diarrhea, H2 on the breath
Term
What two tissues increase GLUT4 expression on the cell surface in response to insulin?
Definition
Adipose and Muscle
Term
Where do we find GLUT1 receptors?
Definition
RBCs and most other cells
Term
What glucose transporter is insulin sensitive?
Definition
GLUT4- Muscle and Fat
Term
Where do we find GLUT2 receptors?
Definition
Intestine, Beta cells of the liver
Term
Where do we find GLUT3 receptors?
Definition
Brain
Term
Where do we find GLUT4 receptors?
Definition
Muscle and Fat
Term
Where do we find GLUT5 receptors?
Definition
Lumen side of intestine
Term
What type of receptor is the insulin receptor?
Definition
Tyrosine Kinase
Term
What enzyme is deficient in Von Gierkes disease and what is the effect of this deficiency?
Definition
Glucose 6- Phosphatase; glycogen stays trapped so: hypoglycemia, enlarged liver and kidney, acidosis, lipemia
Term
What enzyme is deficient in Andersen disease and what is the effect of this deficiency?
Definition
Branching Enzyme; cannot build large, densely branched glycogen so: glycogen looks like a foreign body and the liver reacts- hepatosplenomegaly- Usually Fatal
Term
What enzyme is deficient in McArdles disease and what is the effect of this deficiency?
Definition
Glycogen Phosphorylase in muscle; exercise induced muscular pain, cramps, weakness
Term
What enzyme is deficient in Hers disease and what is the effect of this deficiency?
Definition
Liver Glycogen Phosphatase; Hepatomegaly and hypoglycemia
Term
What enzyme is deficient in Coris disease and what is the effect of this deficiency?
Definition
Debranching enzyme; inability to pick apart glycogen so: milder hypoglycemia, hepatomegaly
Term
What enzyme sequesters glucose in the cell? (1. most tissues; 2. liver)
Definition
1) Hexokinase- non-insulin dependent
2) Glucokinase- Insulin activated
Term
What enzyme converts glucose-6-phosphate back to glucose?
Definition
Glucose-6-Phosphatase
Term
What type of bond is made by Branching Enzyme?
Definition
Alpha 1,6 glucosidic branching from earlier parts of the glycogen backbone
Term
What is the primer for glycogen synthesis?
Definition
Glycogenin
Term
What is the action of Uridyl Transferase (UDP-glucose Pyrophosphorylase)?
Definition
To convert Glucose 1 Phosphate to UDP-Glucose (Releases 2 phosphates)
Term
What is the action of Phosphoglucomutase?
Definition
To convert G-6-P to G-1-P
Term
What is the action of glycogen synthase?
Definition
To elongate glycogen by one sugar
Term
What disease is marked by a deficiency in branching enzyme?
Definition
Andersens' Disease- causes very long unbranched glucose chains that precipitate in the Liver causing HEPATOMEGALY
Term
What enzyme breaks down glycogen, and what activates it?
Definition
Glycogen Phosphorylase;
Glucagon- PKA
Epinephrine- via PKA, PKC, Ca++
Term
What is the product of glycogen breakdown?
Definition
Glucose-6-Phosphate
Term
What disease is marked by a deficiency of debranching enzyme?
Definition
Cori's Disease- Severe hypoglycemia and enlarged liver
Term
A defect in what liver enzyme causes the most severe hypoglycemia, and what is the name of the disease?
Definition
Glucose-6-Phosphatase- Von Gierke's Disease
Term
GLUT4 expression is turned on by activation of which PK complex?
Definition
PKB, activated by PIP3
Term
What is considered a normal blood glucose level?
Definition
80-100 mg/dL
Term
What effect does insulin have on blood glucose?
Definition
Insulin lowers blood glucose
Term
What second messenger is activated after insulin binds to its receptor, and which protein kinase does it activate?
Definition
PIPs; Protein Kinase B
Term
What second messenger is activated after glucagon binds to its receptor, and which protein kinase does it activate?
Definition
cAMP; Protein Kinase A
Term
What is the main driving condition for the breakdown of fat and protein?
Definition
LACK OF INSULIN
Term
Where in the pancreas is glucagon produced, and why is it secreted?
Definition
Alpha Cells in response to low glucose
Term
Where in the pancreas is insulin produced, and why is it secreted?
Definition
Beta Cells in response to high glucose
Term
What effect does epinephrine have on Triglycerides?
Definition
Epinephrine causes breakdown
Term
What is the major consequence of excess glucose acting on proteins?
Definition
Non-enzymatic glycosolation (as in HbA1C)
Term
How does type I diabetes cause a hyper-osmotic coma?
Definition
Pulling water from the cells, especially brain cells
Term
Where is pre-pro-insulin synthesized and cleaved?
Definition
rER
Term
Where is pro-insulin sorted and packaged, and what ion is it packaged with?
Definition
Golgi apparatus, packaged in storage vesicles with Zn
Term
What is cleaved from pro-insulin to activate it, and what is the usefulness of the cleaved part?
Definition
C- peptide (or C-protein)
Can be used as a measure of how much insulin is available, secreted, since it hangs around in spite of the liver using insulin very quickly
Term
What is the effect of ATP on K channels in the pancreatic Islet cells?
Definition
ATP inhibits K+ channels causing DEPOLARIZATION and vesicle release
Term
What is the action of sulfonylurea drugs?
Definition
They trigger INSULIN RELEASE by inhibiting K-ATP channels of Beta cells- basically, they do the same thing as ATP- Ca channels open, the membrane depolarizes, and insulin granules are released
Term
What is the cause of Type I DM?
Definition
Autoimmune destruction of Beta cells
Term
What is the cause of Type II DM?
Definition
Insulin resistance in skeletal muscle and liver
Term
What is MODY?
Definition
Maturity Onset Diabetes of the Young
-DECREASED GLUCOKINASE ACTIVITY which sequesters glucose in the cell
-this means you need MORE GLUCOSE TO GET A REGULAR AMOUNT OF ATP
-INSULIN IS ONLY RELEASED AT HIGH GLUCOSE LEVELS
Term
What two main factors suppress the synthesis of Glucagon?
Definition
Insulin and Glucose
Term
What effect does cortisol have on glucagon release?
Definition
Increase
Term
What effect do high concentrations of amino acids have on glucagon release?
Definition
High concentrations of amino acids (as after a high protein meal) INCREASE glucagon release even if insulin is also high- this increases the conversion of amino acids to glucose
Term
What effect does caffeine have on PKA?
Definition
Caffeine inhibits phosphodiesterase, which breaks down cAMP- as a result, cAMP stays around and accumulates, constantly activating PKA
Term
What is the effect of PKB on glucose transporter GLUT4?
Definition
PKB stimulates the movement of GLUT4 from the internal membrane vesicles to the plasma membrane
INCREASING THE UPTAKE OF GLUCOSE
Term
What organ has the highest glucose demand in the basal state?
Definition
THE BRAIN
Term
Why doesn't glucagon release alter muscle metabolism?
Definition
Muscles lack the glucagon receptor
Term
What is the effect on the liver of a high intake of caffeine?
Definition
Prolonged response to glucagon via prolonged activation of PKA (no breakdown of cAMP)
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