Test 3 - Quan Flashcards
Most important functions of oxygen
Oxygen is essential for all aerobic organisms (oxidative phosphorylation)
Oxygen is ___ at body temperature
Inert
Define Oxidation
The loss of electrons which leads to an increase in the oxidation state
Define Reduction
The gain of electrons which leads to a decrease in the oxidation state
Where are the ROS?
What are the free radicals?
ROS are reactive oxygen species which are oxygen molecules that have one lone electron.
Free radical - A cluster of atoms one of which contains an unpaired electron in its outermost shell of electrons
How are ROS formed?
3 ways:
- Reaction of oxygen with decompatmentalized metal ions
- A side reaction of mitochrondrial electron transport
- Normal enzymatic reactions
Define oxidative stress
An imbalance between the production of free radicals and the ability of the body to counteract or detoxify their harmful effects through neutralization by antioxidants.
How do ROS damage cells?
The cell membrane is full of polyunsaturated fatty acids that readily react with ROS.
Hydroxyl radical reacts with all components of the DNA molecule (purines, pyrimidines, deoxyribose backbone)
Physiological functions of ROS
Help thyroid to make H2O2 to attach iodine atoms to thyroglobulin to make thyroxine
Macrophages and neutrophils must generate ROS to kill some types of bacteria
Defense mechanisms against ROS
- Antioxidant defense
2. Glutathione peroxidase
What are the 3 forms of antioxidant defense?
- Superoxide dismutase converts 2 superoxide anions into H2O2 and oxygen
- Catalase converts H2O2 to water and O2
- Small molecules are antioxidants - Vitamin A, C, E, Uric Acid
What does Glutathione Peroxidase do?
Reduces lipid peroxides through oxidizing glutathione
Important properties of the liver
Central role in metabolism, filtration of ingested materials, and excretory functions
Markers of liver disease
- Mild liver disease: Typically no outward symptoms. Detected only as biochemical changes
- Severe liver Disease: Yellow pigmentation, bruising readily, profuse bleeding, abdomen distended with fluid
- Can lead to Endocrine, CNS, skin, cardiovascular, and GI problems
Special features of liver anatomy
Structure facilitates exchange between hepatocytes and plasma.
Portal vein is found running through it
The liver plays a central role in ____ metabolism
Glucose
The liver maintains circulating ____ of glucose
Concentration
The liver is essential for glucose metabolism because:
- Kidneys do not store glycogen
- Muscles store glycogen (more than the liver) but do not have Glucose-6- phosphatase (enzyme that allows glucose to be released into the blood) so cannot directly contribute to glucose in the blood.
Liver plasma proteins (4)
- Albumin
- Coagulation factors
- Alpha and Beta plasma globulins
- Acute phase proteins
Acute phase proteins are __ ___ proteins that are released by ___ ___ or __ __ during the __ phase response.
C-reactive proteins that are released by damaged tissue or infective agents during the acute phase response
The ___ ___ is essential for the removal of nitrogen generated by the amino acid metabolism
Urea Cycle
What is heme?
Heme is the O2 binding moiety common to Mb and Hb.
What is the rate limiting step in heme synthesis?
Glycine and succinyl-coA condense to form 5-ALA. This reaction is synthesized by 5-ALA synthase in the mitochondria and is the rate limiting reaction
What controls the synthesis of heme?
Heme controls its own synthesis
What is bilirubin?
Bilirubin is the catabolis product of heme
What is jaundice?
Jaundice is when there is an excess of plasma bilirubin as there is an imbalance between its production and secretion.
What are the 3 main causes of jaundice?
- Prehepatic (increased production of bilirubin)
- Intrahepatic (impaired hepatic uptake, conjugation, or secretion of bilirubin)
- Posthepatic (obstruction to biliary drainage)
Explain drug metabolism in the liver
Most drugs are metabolized in the liver through the addition of a polar head group to said drug. This is done by P-450
Describe the active site of Cytochrome P-450
Active site contains a heme iron center that is important for the oxidation of organic substances
Acetaminophen toxicity
In excess, free radical-mediated peroxidation of liver membrane lipids occurs resulting in hepatocellular damage
Alcohol toxicity
Ethanol is oxidized in the liver, mainly by alcohol dehydrogenase, to form acetaldehyde, which is in turn oxidized by aldehyde dehydrogenase (ALDH) to acetate.
What are the 2 major energy sources in the body?
Glucose and fatty acids
Why is glucose so critical?
It fuels the brain and is the preferred energy source in muscle
What’s the long-term energy storage?
Glucose in the form of glycogen
Can you use amino acids as an energy source?
Yes. During fasting or metabolic stress. If excess are ingested, then your body converts them to carbs and stores them.
What is plasma glucose concentration a result of?
Intake, production, and tissue utilization
What cells secrete insulin? What cells secrete glucagon?
Beta cells - Insulin
Alpha cells - Glucagon
What is the source of glucose in a fed state? What is the source in a starving state?
Fed state - diet
Starving state - Glycogen
What are the phases of insulin production after oral glucose?
First phase is form glucose stimulation, then by amino acids through stimulation of the vagus nerve and hormones secreted by the gut
____ results in signaling cascade activating regulatory enzymes in key pathways like ___-__
Insulin
GLUT-4 (a glucose transporter)
What are the effects of insulin?
Promotes anabolism in the liver, adipose tissue, and muscle
What are the causes of type II diabetes?
- Receptor binding compromised
- Mutation in insulin receptor gene
- Anti-receptor autoantibodies
- Inadequate synthesis/secretion
- Inability of insulin to exert a normal effect
What is the function of glucagon?
- Mobilizes glucose
- Increases blood glucose
- Stimulates catabolism
- Suppresses anabolism
What is the function of epinephrine in energy metabolism?
Inhibits glycolysis and lipogenesis.
Stimulates gluconeogenesis.
Phosphorylation in catabolism
Phosphorylation by glucagon stimulation stimulates catabolic enzymes and inhibits anabolic ones
What are the causes of hypoglycemia?
- Exercise
- Fasting
- Excess endogenous and exogenous insulin
- Inhibition of glucose production
Ratios of insulin/glucagon
- After Eating
- During Fasting
- After eating for several hours insulin is high and glucagon is low
- During fasting glucagon is high and insulin is low
What are the 3 substrates for gluconeogenesis?
- Lactate
- Alanine
- Glycerol
What goes to the Cori Cycle?
Glucose released from the liver into the blood stream goes to the Cori Cycle in the muscles
What is the major energy substrate during prolonged starvation?
Free fatty acids
During stress, _anti-insulin hormones are secreted including:
- Epinephrine
- Glucagon
- Cortisol
What are the differences between type 1 and type 2 diabetes?
Type 1 - Is the destruction of beta-cells
Type 2 - Involves insulin resistance and impaired insulin secretion
Diabetics are prone to ____ and are dependent on ____
Ketoacidosis
Insulin
What is the role of obesity in diabetes?
Type 2 is the result of obesity. Weight loss with exercise can often reverse it.
Insulin lack and clinical symptoms
Insulin lack can lead to either increased gluconeogenesis/decreased glucose uptake or increased lipolysis. These have clinical symptoms such as Hyperglycemia, Acidosis, Dehydration, and Hypervantilation.
Diabetic vascular complications?
Hyperglycemia leads to atherosclerosis, microangiopathy, cataracts and eye nerve conduction defects
Explain the glucose tolerance test
Add glucose to the blood stream and monitor the glucose cellular consumption
Explain the A1C test
Hemoglobin can be modified by glycation. The more glucose in the blood leads to the more glycation on hemoglobin. The degree of glycation is an indicator of glucose exposure over the RBC lifespan
What are the treatments for diabetes?
- Diet
- Exercise
- Maintain blood glucose
- Insulin (Type I)
