Exam III final cut Flashcards
Oxygen is reactive/combustable in very
high temp
How are ROS formed?
• Oxygen reacting with a decompartmentalized metal ions, known as the Fenton or Haber-Weiss reaction
How do ROS damage cells?
Cell membrane contains a lot of polyunsaturated fats which are highly reduced = prone to oxidation by ROS.
OH radicals attack DNA and damage pyrimidines, purines, and deoxyribose backbone which is highly susceptible to oxidation
Physiological functions of ROS
Cells of the thyroid make H2O2 to attach iodine atoms to thyroglobulin = thyroxine
Macrophages and neutrophils must generate ROS in their granules to kill some types of bacteria during phagocytosis.
Defense mechanisms against ROS
There are 1. Preventative mechanisms 2. Repair mechanisms 3. Physical defenses. Antioxidant defense (enzymatic defense) Superoxide dismutase (enzyme) converts two superoxide anions into H2O2 and oxygen. Catalase (enzyme): converts H2O2 to water and O2. Small Molecules are antioxidants: Vitamin A,C,E, Uric Acid Glutathione peroxidase: reduces lipid peroxides through oxidizing glutathione. Glutathione is very important to ROS defense
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
Liver plasma proteins
Most plasma proteins synthesized by the liver and include albumin, acute phase proteins, coagulation factors, and alpha and beta plasma globulins
Acute phase protein
C-reactive proteins are seen (are released) due to damaged tissues and infections and are best index of acute phase protein response
Drug metabolism in the liver
Most drugs are metabolized in the liver through the addition of a polar head group to drug. This is done by P-450 cytochrome drug detoxification enzymes.
Acetaminophen toxicity
When acetaminophen is taken in therapeutic doses it is conjugated to glucuronic acid and excreted. 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. Acetaldehyde and acetate are toxic to the body.
Phases of insulin production after oral glucose
First phase is from glucose stimulation, then by amino acids through stimulation of the vagus nerve and hormones secreted by the gut
Function of epinephrine in energy metabolism
• Energy is provided from glucose, fatty acid, and protein catabolism. In times of stress, anti-insulin hormones are produced. Anti-insulin hormones include Epinephrine, cortisol and glucagon. These anti-insulin hormones, like epinephrine, can be used to decrease anabolism (glycogen synthesis), and increase catabolism (glycogenolysis, lipolysis, and proteolysis and increased insulin-dependent glu. Uptake) Glycogenolysis is the conversion of glycogen to glucose for energy use.
Ketoacidosis and type 1 diabetes
• Ketone bodies accumulate in plasma. Increasing blood H+ thus lower blood pH = diabetic ketoacidosis
A1C test
• Hemoglobin can be modified by binding to glucose (glycation). The degree of glycation is an indicator of glucose exposure over the RBC lifespan. Normal A1c is 4-6%. Thus testing A1c can indicate diabetes.
- Know about the similarities between developmental genes from different organisms.
Different organisms can have homologous genes that can function interchangeably. I.e. Example of a mouse that lacks Engrailed-1 gene won’t have a cerebellum but if you transplant that from a fruitfly then the mouse can still develop a cerebellum.
homeotic genes direct regions (segments) to
differentiate into their final forms.
genes can have complex expression patterns by having a series of
control regions directing transcription in different regions of the organism.
homeotic genes are arrayed on the chromosome in the same order as they are
expressed in developing embryos and in the same order in fruit flies and humans.
Interphase
o G1: Growth occurs, cellular contents except for chromosomes are duplicated
o S phase: chromosomes are duplicated
o G2: Growth, cell double checks that chromosomes have not been incorrectly duplicated
Protooncogenes
normal cellular genes that function in cell proliferation (dominant mutant) if 1 allele has mutation cell will be transformed
• Mutated protooncogene
• is an oncogene which is dominant
Tumor suppressor genes
: anti-proliferative genes (recessive) need to lose both allele to become bad
• G1 checks
• is the environment favorable?
• G2 checks
is the DNA replicated? And above questions
• Metaphase checks
are chromosomes attached to spindles
- Know the general pathway for growth factor signaling.
- Signal for proliferation and bind to specific cell receptors
- PDGF: growth factor and receptor oligomerization leading to receptor PTK activation→ Phosphosphorylation of PTK moiety and docking sites form recruiting signaling enzymes
• Cytokines
growth factor binds, oligomerization occurs, then JAKS is recruited and phosphorylates STATS which dimerize and migrate into nucleus to act as transcription factors
- Know the basic types of cancers found in humans
- Epithelial: carcinoma 90%
- Connective/Muscle tissue: Sarcoma
- Hematopoetic: Leukemia
• Dominant cancer
o Viral oncogene that is a mutated homolog of a normal gene
o Gene coming under control of constitutive promoter or enhancer that a virus introduces into the genome
o Insertion of retrovirus can activate protooncogene
o 85% arise from point mutations
• Recessive
o Tumor suppressor gene mutations- p53 lesion
o Retinoblastomas:
• Non-Hereditary- both copies defective in cancer cells
• Factors that PROMOTE the Bone Remodeling Cycle:
o Parathyroid hormone o Parathyroid hormone-related protein o Prostaglandin o Prolactin o IL-1, IL-6, and TNF o Corticosteroids o Vitamin D
• Factors that INHIBIT the Bone Remodeling Cycle:
o Calcium o Estrogens o Calcitonin o Tumor Growth Factor-β o IL-17
(d) How Do Osteoblast Regulate Osteoclasts?
• PTH binds to osteoblasts to stimulate osteoclast precursors to fuse and become osteoclasts
- Parathyroid Hormone Regulation of Calcium Levels
• PTH stimulates osteoclast-mediated bone resorption
(b) What Regulates PTH Production?
- decrease plasma calcium levels PTH production
* increase plasma calcium levels PTH production
PTH
increases blood calcium levels
What are the Consequences of Increased Vitamin D
Increases serum calcium, absorbs calcium from diet and increases storage of calcium in bone
Detection with Intact Parathyroid Hormone
production of too much PTH could be causing an influx of Ca2+ in the bloodstream leading to muscle cramps, abdominal pain and tingling in fingers and toes, usually indicative of hypercalcemia when accompanied by high calcium levels
Tumor Production of Parathyroid Hormone Related Protein
Has a sequence homology with parathyroid hormone but leads to:
• Hypophosphatemia: low levels of blood phosphate
• Phosphaturia
• Increased renal calcium resorption
• Osteoclast activation
- Hypocalcemia major causes
o Hypoparathyroid: postoperative, idiopathic, acquired hypomagnesemia, neck irradiation, anticonvulsant therapy
o Non-parathyroid: vit D deficiency, malabsorption, liver disease, renal disease, vit D resistance
o PTH resistance: pseudo-hypoparathydrodism, hypomagnesemia
• Chveostek’s Sign
twitching of facial muscles in response to tapping over area of facial nerve
• Trousseau’s Sign
carpopedal spasm caused by inflating the blood pressure cuff to a level above systolic pressure for 3 minutes
Intrinsic enzymatic activity receptors
• Ligand-triggered protein kinases
• Similar to tyrosine-linked receptors (form dimers upon ligand binding)
• Ligand/receptor complex directly acts as a tyrosine kinase (phosphorylates other kinases)
o Phosphorylation activates other protein kinases
• Arachidonic acid conversion to prostaglandins involves a cyclooxygenase isoforms
o COX-1 (constitutive) and COX-2 (response to inflammatory mediators)
o Stimulate inflammation, regulate blood flow to organs such as the kidney, control ion transport across membranes, modulate synaptic transmission, and induce sleep
