Exam Flashcards
What are the so-called brain-gut peptides?
a. ) Peptides originally discovered in gastrointestinal tract and later found in the brain
b. ) In brain they function as neurotransmitters and neuroimediators.
Describe the renin-angiotensin system; which steps can be inhibited by drugs?
a. ) When renin is released into the blood, it acts upon a circulating substrate, angiotensinogen, that undergoes proteolytic cleavage to form the decapeptide angiotensin I. Surface of pulnorary and renal endothelium (lungs, liver) has an enzyme, angiotensin converting enzyme (ACE), that cleaves off two amino acids to form the octapeptide, angiotensin II (AII), which functions via 4 GPCR receptors AT1, AT2, AT3, AT4. It increases blood pressure by stimulatin Gq protein in vascular smooth muscle cells (which in turn activates contraction by an IP3-dependant mechanism)
b. ) Cleaving off two amino acids from AI (ACE inhibitors), binding of angiotensin to receptors (inhibitors of angiotensin receptors (ARBs)), binding of neurotransmitter to beta adrenergic receptors, movement of Ca2+ through calcium channels (calcium channel blockers), diuretics (natriuresis)
Draw schematically plasma membrane and name its main components.
Lipids (glycerophospolipids, sphingolipids, cholesterol), proteins (enzymes, receptors, ion channels, transporters, hormones) and oligosacharides
What are inborn metabolic diseases, what is causing them. Name at least one and describe its impact on organism?
a.) Are rare genetic or inherited disorders resulting from an enzyme defect in biochemical and metabolic pathways (affecting proteins, fats, carbohydrates metabolism or impaired organelle function). The disorders are usually caused by defects in specific proteins (enzymes) that help break down (metabolize) parts of food.
b.) Disorder of phenylalanine metabolism, disorder of methionine and cysteine metabolism, disorders of tyrosine metabolism, glutaric aciduria, deficiency in tryptophan metabolism, MSUD (maple syrup urine disease)
• MSUD
o ketoacidurie – Leu, Ille, Val and their toxic by-products accumulate in blood and urine. The patients excrete branched chain alfa keto acids, corresponding hydroxy acids and other side products which have characteristic odor as maple syrup - mental retardation, short life span
• Albinism (disorders of tyrosine metabolism)
o lack of tyrosine (enzyme involved in the production of melanin) - lack of melanin - sensitivity to sun, increasing incidence of skin cancer, photophobia
• Phenylketonuria (disorder of phenylalanine metabolism)
o excretion of phenylketon, phenylacetic acid in the urine
o mice-like smell of urine
o if not treated – mental retardation
What are acute phase proteins?
A class of proteins whose plasma concentrations increase (positive APP or AP reactants) or decrease (negative APP or AP reactants) in response to: infection, inflammation, trauma, burns, etc.
• Increase of: C-reactive protein, procalcitonin, caeruloplasmin, etc.
• Decrease of: albumin, prealbumin, transferrin
What do you know about lactate dehydrogenase?
a.) It catalises the conversion of pyruvate to lactate
b.) It’s activity is measured by monitoring absorbance at λ = 340 nm (NADH) or other when using coupled color reaction
c.) Total LD activity has poor specificity
d.) LD isoenzymes are mostly found in heart, RBC, kidney, brain, liver, skeletal muscle
e.) LD isoenzyme electrophoresis (normal serum): LD-2 > LD-1 > LD-3 > LD-4 > LD-5
f.) It is an enzyme marker used in differential diagnosis of myocardial infarction
• five isoenzymes, composed of combinations of H (heart) and M (muscle) subunits
Which are the main aminotransferases used in diagnosis and what is their meaning in the diagnostic tests?
a.) Alanine aminotransferase
• now it is part of diagnostic liver function tests, to determine liver health
• it is raised in blood in acute liver damage
b.) Aspartate aminotransferase
• it is commonly measure clinically as a part of diagnostic liver function test (more important than AST)
• identify liver disease, especially cirrhosis and hepatitis caused by alcohol, drugs or viruses
• help to check for liver damage
• find out whether jaundice was cause by a blood disorder or liver disease
• follow the effects of cholesterol-lowering medicines and other medicines that can damage the liver
Describe standard thyroid function test.
The T4 test and the TSH test are the two most common thyroid function tests. They’re usually ordered together.
• The T4 test
o total T4 - which measures the entire amount of thyroxine in the blood, including the amount attached to blood proteins that help transport the hormone through the bloodstream
o free T4 - which measures only the thyroxine that’s not attached to proteins (this is the portion of T4 in the blood that’s available to affect the functioning of many types of body cells)
• The TSH test measures the level of thyroid-stimulating hormone in your blood.
Name hormones derived from amino acids, their function and mechanism of action.
a.) Thyroxine and Triiodothyronine
• Both T4 and T3 regulate the metabolism and affect the growth and rate of function of many other systems in the body
• The thyroid hormones function via a well-studied set of nuclear receptors, termed the thyroid hormone receptors. When triiodothyronine (T3), which is the active form of thyroxine (T4), binds a receptor, it induces a conformational change in the receptor, displacing the corepressor from the complex. This leads to recruitment of coactivator proteins and RNA polymerase, activating transcription of the gene.
b.) Catecholamins
• They cause general physiological changes that prepare the body for physical activity (the fight-or-flight response). Some typical effects are increases in heart rate, blood pressure, blood glucose levels, and a general reaction of the sympathetic nervous system.
• In the blood, catecholamines target alpha and beta-adrenergic receptors, a family of g protein coupled receptors (GPCRs). The adrenergic receptors utilize either cAMP or phosphoinositol second messenger systems to activate ion channels that ultimately mediate the body’s sympathetic response.
Inhibitors of fatty acid reabsorption, bile acid binding resins, statins, plant sterols – what do they do and how? Describe for at least two molecules/molecule types
a. ) Lipofermata: inhibits the transport through a non-competitive process in blocking the transport of long and very long chain fatty acids ?
b. ) Orlistat: prevents the absorption of fats by inhibiting pancreatic lipase, which can break down triglycerides in the intestine to decrease the caloric intake
c. ) C75: acts on KR, ACP and TE domains of FAS as a competitive irreversible inhibitor
d. ) Orlistat (inhibitor of fatty acid absorption): prevents the intestinal absorption of about 30% of fat from the diet. It is a gastric and pancreatic lipase inhibitor; inhibits both gastric and pancreatic lipases, the key enzymes that break down triacylglycerols in the small intestine.
e. ) Atorvastatin (statin): effective in lowering LDL cholesterol. It is a competitive inhibitor of HMG-CoA reductase. Inhibition of the enzyme decreases de novo cholesterol synthesis.
f. ) Bile acid binding resins: bile acid sequestrants exchange anions such as chloride ions for bile acids. By doing so, they bind bile acids and increase the excretion of bile acids. This reduces the amount of bile acids returning to the liver and forces the liver to produce more bile acids to replace the bile acids lost sequester them from the enterohepatic circulation. Because the body uses cholesterol to make bile acids, this reduces the level of LDL cholesterol circulating in the blood.[
Name at least 3 steroid hormones and their function in the organism.
a. ) Estrogens: They promote development of female sex characteristics and skeletal growth.
b. ) Cortisol: Aids in metabolism regulation by stimulating the production of glucose from non-carbohydrate sources in the liver. Cortisol is also an important anti-inflammatory substance and helps the body deal with stress.
c. ) Testosterone: It is responsible for the development of male reproductive organs and male secondary sex characteristics.
Name consequences of high and low cholesterol levels.
a. ) Elevated levels of cholesterol in the blood lead to atherosclerosis which may increase the risk of heart attack, stroke, and peripheral vascular disease
b. ) Low levels of cholesterol are termed hypocholesterolemia. Researchers suggest that because cholesterol is involved in making hormones and vitamin D, low levels may affect the health of your brain; may trigger hormonal imbalances.
Which enzyme is the key enzyme in biosynthesis of cholesterol and how can we inhibit it?
a. ) 3-hydroxy-methylglutaryl-CoA reductase (HMG-CoA reductase)
b. ) Statins - HMG-CoA reductase inhibitors
What are statins and what is mechanism of their action.
a. ) Statins are HMG-CoA reductase inhibitors
b. ) Statins act by competitively inhibiting HMG-CoA reductase, the rate-limiting enzyme. Because statins are similar in structure to HMG-CoA on a molecular level, they will fit into the enzyme’s active site and compete with the native substrate (HMG-CoA). This competition reduces the rate by which HMG-CoA reductase is able to produce mevalonate.
What is cholesterol, what are its functions, describe methods of its determination.
a.) Cholesterol is a sterol
b.) Main component of cell membranes (it regulates membrane fluidity), precursor of bile acids, major precursor for the synthesis of vitamin D, involved in metabolism of the other fat-soluble vitamins, precursor of steroid hormones, important part of neurons in myelin (it helps to conduct nerve impulses), participate in the formation of lipid rafts in the plasma membrane, etc.
c.) Methods:
• Triacylglycerol (TAG) determination
• Total cholesterol determination
o 1/3 cholesterol free in plasma, 2/3 in the form of esters
o It is either chemical or enzymatic
a. Chemical - cheaper, less precise less specific, less exact
i. reaction with sulfuric acid and acetyl anhydride – green product
b. Enzymatic - more expensive, more specific, more accurate
i. hydrolysis using cholesterase
ii. oxidation to get cholest-4-en-3-on and hydrogen peroxide by cholesteroloxidase
iii. determination of hydrogen peroxide using indicator or coupled reaction (catalase and aldehyd dehydrogenase)
• HDL-cholesterol determination
o HDL is measured directly in serum
• LDL-cholesterol determination
o LDL-cholesterol is calculated from measured values of total cholesterol, triglycerides and HDLcholesterol
Describe the role of bile acids and their metabolism.
a.) They are critical for digestion and absorption of fats and fat-soluble vitamins in the small intestine. Many waste products, including bilirubin, are eliminated from the body by secretion into bile and feces.
b.) The excretion and reabsorption of bile acids form the basis of the enterohepatic circulation which is essential for the digestion and absorption of dietary fats (and plenty of other molecules.
They are synthesized by oxidation of cholesterol and are then conjugated with glycine, taurine, glucuronic acid, or sulfate for secretion into bile. Bile salts form mixed micelles with phospholipids and cholesterol and stored in the gallbladder, secreted into the intestinal tract to facilitate digestion and absorption of nutrients. Most bile acids are reabsorbed in the ileum and are transported back to the liver via portal blood circulation to inhibit bile acid synthesis.
What is bile? Describe its turnover.
a.) A mixture of conjugated and non-conjugated bile acids along with cholesterol itself which is excreted from the liver
b.) Bile acids are conjugated with glycine, taurine, glucuronic acid, or sulfate for secretion into bile. Bile salts form mixed micelles with phospholipids and cholesterol and stored in the gallbladder, secreted into the intestinal tract to facilitate digestion and absorption of nutrients.
Initially, hepatocytes secrete bile into canaliculi, from which it flows into bile ducts. This hepatic bile contains bile acids, cholesterol, phospholipids, bilirubin, and other organic xeno substances. As bile flows through the bile ducts in the second stage, it is modified by addition of a watery, bicarbonate-rich secretion from ductal epithelial cells.
In species with a gallbladder, bile is stored in the gallbladder. The gallbladder concentrates bile during the fasting state. Typically, bile is concentrated fivefold in the gall bladder by absorption of H2O and electrolytes across the gallbladder mucosa. Bile is ultimately secreted into the intestine during a meal, where it aids in the digestion and absorption of dietary lipids.
What is bilirubin? What means high bilirubin in plasma?
a. ) Is an orange-yellow substance made during the normal breakdown of red blood cells waste product.
b. ) It’s a sign that either your red blood cells are breaking down at an unusual rate or that your liver isn’t breaking down waste properly and clearing the bilirubin from your blood.
Describe endocrine and exocrine function of pancreas.
a. ) Endocrine: it functions mostly to regulate blood sugar levels, secreting the hormones insulin, glucagon, somatostatin, and pancreatic polypeptide.
b. ) Exocrine: as a part of the digestive system; secreting pancreatic juice. This juice contains bicarbonate, which neutralizes acid entering the duodenum from the stomach; and digestive enzymes, which break down carbohydrates, proteins, and fats in food entering the duodenum from the stomach.
What is cholestasis?
Is a reduction or stoppage of bile flow caused by disorders of the liver, bile duct, or pancreas.
Describe the hypothalamo-pituitary-adrenal axis – name examples of the produced and regulated hormones.
a. ) Produced: corticotropin-releasing factor (CRF), cortisol
b. ) Regulated: adrenocorticotropic hormone (ACTH), glucocorticoid
Explain the terms: endocrine, paracrine, autocrine, neurocrine.
a. ) Endocrine: pertaining to hormones and the glands that make and secrete them into the bloodstream through which they travel to affect distant organs. (a cell targets a distant cell through the bloodstream)
b. ) Paracrine: relating to the release of locally acting substances from endocrine cells. (a cell targets a nearby cell)
c. ) Autocrine: of or relating to self-stimulation through cellular production of a factor and a specific receptor for it. (a cell targets itself)
d. ) Neurocrine: neuron secretes signal molecule. Signal molecule acts as a neurotransmitter (NT), which acts on receptors on neighbor (gland, another neuron or muscle). Acts locally.
Which hormones modulate calcium homeostasis? How the level of calcium is being determined?
a. ) Parathyroid hormone (PTH), calcitonin
b. ) A blood sample is taken. There are two tests to measure blood calcium. The total calcium test measures both the free and bound forms. The ionized calcium test measures only the free, metabolically active form. If a urine collection is required, a 24-hour urine sample or a timed collection of a shorter duration is obtained.
Order lipoproteins (lipid particles) according to density and content of cholesterol.
a. ) Density: HDL > LDL > IDL > VLDL > chylomicrons
b. ) Content of cholesterol: LDL (CEs) > IDL (TGs) > VLDL (TGs) > HDL (CEs) > chylomicrons (TGs)
Name the main lipoproteins (lipid particles) which occur in blood and describe them.
They all enable fats and cholesterol to move within the water-based solution of the bloodstream
a. ) HDL (high-density lipoprotein): HDL is the smallest of the lipoprotein particles. It is the densest because it contains the highest proportion of protein to lipids. HDL transports cholesterol mostly to the liver or steroidogenic organs such as adrenals, ovary, and testes by both direct and indirect pathways.
b. ) LDL (low-density lipoprotein): it delivers fat molecules to cells. LDL particles are formed as VLDL lose triglyceride and they become smaller and denser. LDL can be grouped based on its size: large low density LDL particles are described as pattern A, and small high density LDL particles are pattern B. It can contribute to atherosclerosis if it is oxidized within the walls of arteries.
c. ) IDL (intermediate-density): are formed from the degradation of very low-density lipoproteins as well as high-density lipoproteins. Each native IDL particle consists of protein that encircles various lipids, enabling these lipids to travel in the aqueous blood environment as part of the fat transport system within the body. Their size is, in general, 25 to 35 nm in diameter, and they contain primarily a range of triacylglycerols and cholesterol esters.
d. ) VLDL (very low density): VLDL particles have a diameter of 30–80 nm. It is assembled in the liver. VLDL is converted in the bloodstream to LDL and IDL. It transports endogenous products.
e. ) Chylomicrons: due to their density relative to lipoproteins, they are also commonly known as ultra low-density lipoproteins (ULDL). They transport exogenous (dietary) products from the intestines to other locations in the body.
What is the role of liver in the lipid metabolism?
a. ) The liver is extremely active in oxidizing triglycerides to produce energy. The liver breaks down many more fatty acids that the hepatocytes need, and exports large quantities of acetoacetate into blood where it can be picked up and readily metabolized by other tissues
b. ) Synthesis of lipoproteins
c. ) Converting excess carbohydrates and proteins into fatty acids (if overproduction of acetyl-CoA) and triglyceride
d. ) Synthesis of cholesterol and phospholipids. Some of this is packaged with lipoproteins and made available to the rest of the body. The remainder is excreted in bile as cholesterol or after conversion to bile acids.
Explain principles of determination of lipoprotein
Lipoprotein distribution (electrophoresis) • Serum lipoproteins were separated by electrophoresis on nondenaturing polyacrylamide gradient gels according apoprotein determination (most often apoA-I and apo-B) • Immunoblot analysis of the apolipoprotein composition of the particles separated by polyacrylamide gradient gel electrophoresis (GGE) under nondenaturing conditions. The reactions of antibodies to apoA-I, apoA-11, apoE, apoB, apoD, and apoA-IV have revealed discrete bands of particles which differ widely in size and apolipoprotein composition
What kinds of lipids are based on glycerol?
Triacylglycerols and glycerophospholipids
