Quan Study Guide Flashcards
What are the most important functions of oxygen?
essential for all aerobic organisms (oxidative phosphorylation
What happens to oxygen at high temps? body temp?
High = highly combustible Body = inert
What is oxidation?
loss of electrons leading to an increase in oxidation state
What is reduction?
gain of electrons leading to a decrease in oxidation state
What are ROS?
reactive oxygen species which are oxygen molecules (sometimes connected to other atoms) that have one lone e-
(partially reduced reactive forms of oxygen)
What are free radicals?
cluster of atoms, one of which contains unpaired electron in outermost shell of electrons
- quickly react with other molecules to obtain a stable configuration
What occurs in the reduction of O2?
1st reduction results in superoxide (O2 with free radical)
2nd reduction results in hydrogenate peroxide
Others include hydroxyl radical (OH), hypochlorite ion and hydroperoxyl radical
How are ROS formed?
- reaction of O2 with decompartmentalized metal ions (Fenton or haber-weiss reaction)
- As a side reaction of mitochondrial electron transport
- Normal enzymatic reactions
When does oxidative stress occur?
when rate of ROS generation exceeds the ability to neutralize them
How do ROS damage cells?
lipid peroxidation
- causes damage to main cellular components
- cell membrane one of most sensitive sites to ROS damage
- cysteine and methionine susceptible to oxidation by ROS
What are the physiological functions of ROS?
- Cells of thyroid must make H2O2 to attach iodine atoms to thyroglobulin to make thyroxine
- macrophages and neutrophils must generate ROS to kill some types of bacteria
What are some defense mechanisms against ROS?
- preventative mechanisms
- repair mechanisms
- physical defenses
- enzymatic
- superioxide dismutase converts 2 superoxide anions to hydrogen peroxide and O2
- catalase converts hydrogen peroxide to water and oxygen - antioxidant
Where are ROS most prevalent?
in blood and tissues as hydrogen peroxide
What types of molecules are antioxidants?
Vitamins A, C and E and uric acid
What does glutathione peroxidase do?
reduces lipid peroxides through oxidizing glutathione
- very important in ROS defense
What are some important properties of the liver?
central role of metabolism, filtration of ingested materials and excretory functions
What are some markers of mild liver disease?
typically no outward symptoms. Detected only as biochemical changes
What are some markers of severe liver disease?
yellow pigmentation, bruising readily, profuse bleeding, abdomen distended with fluid
What problems can liver disease lead to?
endocrine, CNS, skin, cardiovascular and GI problems
What are some special features of the liver?
- structure facilitates exchange between hepatocytes and plasma
- portal vein is found running through it
What plays a central role in glucose metabolism?
liver
How does the liver play a role in glucose metabolism?
Maintains circulating concentration of glucose
Why is the liver essential for glucose metabolism?
- kidneys do not store glycogen
- muscles store glycogen (more than the liver) but do not have glucose-6-phosphatase which allows glucose to be release into blood.
What are the liver plasma proteins?
albumin, coagulation factors, alpha and beta plasma globulins, acute phase proteins
What do acute phase proteins do?
C-reative proteins (proteins that measure general levels of inflammation in the blood) are released by damaged tissue or infective agents during actor phase response
Why is the urea cycle important?
removal of nitrogen generated by amino acid metabolism
What does catabolism of amino acids generate?
ammonia and ammonium ions (toxic to CNS)
How is ammonia detoxified?
on site by admiration of glutamate to glutamine
What happens to remaining nitrogen?
enters the portal vein as ammonia or alanine so the liver can convert the ammonia/ammonium to urea for excretion
What is heme?
O2 binding moiety common to Mb and Hb
Where does heme synthesis occur?
1st in the mitochondria, then the cytoplasm then back to the mitochondria
What is the rate limiting step during heme synthesis?
glycine and succinyl-coA condense to form 5-ALA. This reaction is synthesized by 5-ALA synthase in the mitochondria
T/F Heme controls its own synthesis
T; hemne inhibits 5-ALA synthase
What is bilirubin?
product of heme catabolism excreted in bile and urine
What is jaundice?
when there is excess of plasma bilirubin as there is an imbalance between its production and secretion
What are the three main causes of jaundice?
Prehaptic: increased production of bilirubin as a result of hemolysis
Intrahepatic: impaired hepatic uptake, conjugation or secretion of bilirubin
Posthepatic: obstruction to biliary drainage (in complete obstruction urobilinogen and urobilin are absent from urine)
Is bilirubin soluble?
No, requires carrier protein; biliverdin is
Where are drugs metabolized?
- most in the liver
How are drugs metabolized?
Phase I = addition of polar group mediated by cytochrome P-450
Phase II = conjugation mediated by cytoplasmic emzymes (sulfation, acetylation, methylation)
What role does cytochrome P-450 play in drug metabolism?
active site contains a heme iron center that is important for oxidation of organic substances
What happens when acetaminophen is taken in therapeutic doses?
it is conjugated to glucouronic acid and excreted
What happens when acetaminophen is taken in excess?
produces free radical (causes toxicity), hepatotoxic in excess
What is the most common cause of liver disease?
excess intake of alcohol
Why is glucose critical?
fuels the brain and is preferred energy source in muscle
What is the long-term energy storage of glucose?
glycogen
Can AA be used as an energy source?
Yes, during fasting or metabolic stress. If excess are ingested in diet they are converted to carbs and stored
What is plasma glucose concentration the result of?
intake, production and tissue utilization
What types of cells produce insulin and glucagon?
insulin is secreted by beta cells and glucagon is secreted by alpha cells (both from pancreatic cells)
What is the source of glucose in FED and starving states?
In fed state it is from the diet but in starved states it is from glycogen
What are the phases of insulin production after oral glucose?
1st phase is from glucose stimulation, them by AA through stimulation of the vagus nerve and hormones secreted by the gut
What are some effects of insulin?
promotes anabolism in the liver, adipose tissue and muscle
What are the causes of type 2 diabetes?
insulin resistance and impaired insulin secretion
What role does GLUT4 play with insulin in the cell?
insulin dependent glucose entry into the cell is mediated by glucose transporters (GLUT4)
- controls glucose uptake in skeletal muscle and adipocytes
Where doe most GLUT4 molecules reside?
intracellularly
Why does insulin double rescruitment of the transporter to the cell membrane in humans?
- muscular contraction increases expression of GLUT4 independently of insulin
- fatty acids decrease expression of GLUT4 in muscle
What are the effects of insulin
promotes anabolism in the liver, adipose tissue and muscle
What are main contributors of type 2 diabetes?
inadequate synthesis, secretion, most commonly unable to exert normal effect
What results from defects in insulin signaling?
receptor binding could be compromised, mutation in the insulin receptor gene or anti-receptor autoantibodies could be in effect
What is the function of glucagon?
mobilizes glucose, increases blood glucose, stimulates catabolism, surpasses anabolsim
What are the function of epinephrine in energy metabolism?
Secreted by adrenal gland, inhibits glycolysis, lipogenesis, stimulates gluconeogenesis
What occurs during phosphorylation in catabolism?
glucagon stimulates activation of Fru-2,6-Bisphosphate causing decrease if Fru-2,6-BP which has a reciprocal inhibitory effect on mainline PFK1 inhibiting glycolysis
What does glucagon action result in?
stimulation of gluconeogenesis and inhibition of glycolysis
What does phosphorylation typically stimulate?
enzymes in catabolic pathways and inhibits anabolic ones
What are causes of hypoglycemia?
exercise, fasting, excess endogenous and exogenous insulin, inhibition of glucose production
What controls the Feed-fast cycle?
changes in plasma ratios of insulin and glucagon (ratios of insulin/glucagon)
What are the significant ratios of insulin/glucagon?
after eating for several hours = insulin high/glucagon low
During fasting = glucagon his/insulin low
Starvation = low insulin and high glucagon
What are the substrates for gluconeogenesis?
lactate, alanine, glycerol
What is the cori cycle?
allows recycling of glucose back to lactate
What is the major energy substrate during prolonged starvation?
free fatty acids
during starvation gluconeogenesis occurs in kidney and liver
What anti-insulin hormones are secreted during stress metabolism?
epinephrine, glucagon, cortisol
What is the response during stress?
decreased anabolism and increased catabolism
What are the outcomes of the stress response?
induces insulin resistance, cortisol decreases GLU4
expression and induces expression of G6P
Glucose independent glu uptake increase
What are the differences between type 1 and 2 diabetes?
type 1 is the destruction of beta cells while type 2 involves insulin resistance and impaired insulin secretion
T/F Type one diabetes in not an inherited disease
F
Who is prone to ketoacidosis and dependent on insulin?
diabetics
What role does ketoacidosis play in type 1 diabetes?
ketone bodies accumulate in plasma increasing blood H+ and lowering blood pH = diabetic ketoacidosis
- major complication of poorly controlled diabetes
Which type of diabetes is the result of obesity?
Type 2 but weight loss with exercise can often reverse it
Which type of diabetes is macroangiopathy more prevalent in?
2
What are the clinical symptoms of lack of insulin?
increased lipolysis -> increased ketogenesis -> acidosis -> compensatory hyperventilation
Increased gluconeogenesis -> hyperglycemia -> glycosuria + acidosis -> osmotic diuresis -> dehydration
What are the vascular complications with diabetes?
Hyperglycemia leads to atherosclerosis, microangiopathy, cataracts and eye nerve conduction defects
What is the glucose tolerance test?
add glucose to blood stream and monitor glucose cellular consumption
What is the A1C test?
hemoglobin can be modified by glycation, more glucose in blood leads to more glycation on hemoglobin. Degree of glycation is an indicator of glucose exposure over RBC lifespan
What are treatments for diabetes?
type 1 = diet, exercise, maintain blood glucose, use of insulin
type 2 = treat with oral hypoglycemic drugs(sulfonylureas and thiazolidineadiones)
