Term
| What is used in order to prenylate small, GTP-binding proteins for anchoring into the cell membrane? |
|
Definition
| Geranylpyrophosphate and Farnesylpyrophosphate |
|
|
Term
| What is Farneylpyrophosphate a precursor for? |
|
Definition
Ubiquinone synthesis like CoQ
Dolichol |
|
|
Term
| What are farneylpyrophosphates important for? |
|
Definition
CoQ: ETC in the mitochondria
Dolichol: N-glycosylated proteins in ER |
|
|
Term
| What is the precursor for Vit D3 synthesis in the skin? |
|
Definition
|
|
Term
| What are the uses of cholesterol? |
|
Definition
Bile salt synthesis
Steroid Hormone synthesis
Cell membrane maintenance
Modification of hedgehog |
|
|
Term
| Where will an insufficient synthesis of farnesylpyrophosphate and geranylpyrophosphate affect cells? |
|
Definition
| Inner plasma membrane of cells |
|
|
Term
| How will CoQ synthesis impairment affect cells? |
|
Definition
| ETC cannot make ATP and free radicals increase. |
|
|
Term
| What role do N-glycosylated proteins play in the cell? |
|
Definition
| Cell membrane adhesion, reception, and cell-matrix adhesion molecules. |
|
|
Term
| Where does the synthesis of Bile Salts occur? |
|
Definition
|
|
Term
| What causes gallstone formation (cholelithiasis)? |
|
Definition
| Aggregation of cholesterol or bilirubin in the absence of bile salts. |
|
|
Term
| What catalyzes the first step of bile salt synthesis (formation of cholic acid production)? |
|
Definition
| Cholesterol 7-alpha-hydroxylase |
|
|
Term
| A loss of function of CYP7A1 gene will result in what? |
|
Definition
| High liver cholesterol and high plasma LDL-cholesterol levels with marked low levels of bile salt in the stools. |
|
|
Term
| What are the primary results of conversion of bile salts in the liver? |
|
Definition
Greatly reduced levels of plasma LDL-cholesterol in the plasma
Increased effects of Statin |
|
|
Term
| What is the rate-limiting enzyme of Bile Salt synthesization? |
|
Definition
CYP7A1 in ER
CYP27A1 in mitochondria |
|
|
Term
| What causes feedback inhibition of 7 alpha-hydroxylase? |
|
Definition
|
|
Term
| Where does the intermediate reaction for Bile Synthesis occur? |
|
Definition
|
|
Term
| What are the secondary bile salts? |
|
Definition
Deoxycholic acid from cholic acid
Lithocholic acid from chenodeoxycholic acid |
|
|
Term
| How are bile salts presented at neutral pHs? |
|
Definition
| depronated as sodium salts |
|
|
Term
| What is the most common cause of gallstones? |
|
Definition
| Lack of adequate bile salts in the gall bladder to emulsify cholesterol and or bilirubin |
|
|
Term
|
Definition
| Bile salt accumulation inside hepatocytes. |
|
|
Term
|
Definition
| Generalized itch of the whole body |
|
|
Term
| Why does liver disease cause pruritus? |
|
Definition
Toxins and irritants build up and cause build up in the blood and deposit in the skin.
Also, neuro damage is suspected |
|
|
Term
| What do steroid horomones use as a precursor? |
|
Definition
|
|
Term
| How are steroids secreted? |
|
Definition
| They are lipid soluble so they are freely permeable to membranes |
|
|
Term
| What are the major types of steroid hormones? |
|
Definition
Progestogens: Progesterone
Glucocorticoids: Cortisol
Androgens: Testosterone
Mineralcorticoids: Aldosterone
Estrogen: Estradiol and Estrone |
|
|
Term
| What's the role of Progesterone? |
|
Definition
| Prepares uterus lining for implantation of ovum? |
|
|
Term
| What's the role of Glucocorticoids? |
|
Definition
Gluconeogenesis and fat/protein mobilization.
Anti-inflammation |
|
|
Term
| What is the role of Androgens? |
|
Definition
| Development of male secondary sex characteristics and prevention of bone resorption |
|
|
Term
| What is the role of Estrogen? |
|
Definition
| Development of secondary female sex characteristics and prevention of bone resorption |
|
|
Term
| What are the transporters for Bile Salts from the liver into the gallbladder? |
|
Definition
|
|
Term
| What is the rate-limiting step of Steroid synthesis? |
|
Definition
| Transport of free cholesterol from the cytoplasm to the mitochondria |
|
|
Term
| What does the transport of free cholesterol from the cytoplasm to the mitochondria depend on? |
|
Definition
|
|
Term
| What is Congenital Adrenal Hyperplasia (CAH)? |
|
Definition
| Inadequate cortisol production with an increased risk of fasting hypocglycemia development |
|
|
Term
| What will 21-alpha-hydroxylase cause? |
|
Definition
| Aldosterone synthesis deficiency |
|
|
Term
| What will 17-alpha-hydroxylase defect cause? |
|
Definition
| Cortisol, Testosterone, and Estrogen synthesis deficiency |
|
|
Term
| What will 11-beta-hydroxylase defect cause? |
|
Definition
| Cortisol synthesis deficiency |
|
|
Term
| What does chronically deficient production of cortisol cause? |
|
Definition
|
|
Term
| Why does CAH cause adrenal hyperplasia? |
|
Definition
| High levels of ACTH are released in response to chronically low levels of cortisol |
|
|
Term
| What are the effects of CAH caused by 11-beta-hydroxylase deficiency? |
|
Definition
High DOC (low renin hypertension=>low aldosterone)
High Testosterone (Virilization)
|
|
|
Term
| What are the effects of CAH caused by 17-alpha-hydroxylase deficiency? |
|
Definition
High Aldosterone => hypertension
Low sex steroids => feminization by default |
|
|
Term
| What are the effects of CAH caused by 21-alpha-hydroxylase deficiency? |
|
Definition
Low aldosterone => hypertension
High Testosterone => Virilization |
|
|
Term
| What does DOC or aldosterone accumulation cause? |
|
Definition
|
|
Term
| What does androgen accumulation cause? |
|
Definition
|
|
Term
| What causes Cushing's Syndrome? |
|
Definition
| Prolonged exposure to either endogenous or exogenous glucocorticoids |
|
|
Term
| What are the three types of endogenous Cushing Syndrome causes? |
|
Definition
Pituitary
Adrenal
Ectopic |
|
|
Term
| How do you evaluate the etiology of Cushing's? |
|
Definition
| ACTH test and high dose Dex supression test |
|
|
Term
| Which Cushing syndrome is affected by high-dose Dex suppresion? |
|
Definition
|
|
Term
| Which Cushing's has lowered levels of Serum ACTH? |
|
Definition
|
|
Term
| What is required for Vitamin D3 synthesis in the Skin? |
|
Definition
|
|
Term
| What factors govern the synthesis of Vitamin D3 in the skin? |
|
Definition
| Quantity of UVB, Quality of UVB, and amount of 7-dehydrocholesterol in the skin |
|
|
Term
| Where does Vitamin D3 synthesis occur? |
|
Definition
| Stratum spinosum and stratum basale |
|
|
Term
| What are the two locations of Vitamin D3 metabolism? |
|
Definition
Liver (cholecalciferol 25-hydroxylase)
Kidney (25-hydroxycalciferol 1-alpha-hydroxylase) |
|
|
Term
| What is the biologically active form of Vitamin D3? |
|
Definition
| 1,25-dihydroxycholecalciferol (calcitrol) |
|
|
Term
| How does Vitamin D3 get to target tissues? |
|
Definition
| It binds to vitamin D-binding proteins (VDBP) |
|
|
Term
| How is vitamin D able to act as a transcription factor to modulate the expression of Vitamin D-responsive genes? |
|
Definition
| Calcitrol binds to Vitamin D receptors (VDR) inside the nuclei of target cells |
|
|
Term
| What plasma concentration levels regulate 1,25-dihydroxyvitamin D3? |
|
Definition
|
|
Term
| What will decreased phosphate plasma levels cause? |
|
Definition
Direct activation of 25-hydroxycholecalciferol-1-alpha-hydroxylase
Increased synthesis of 1,25-dihydroxyvitamin D3 |
|
|
Term
| What does PTH in the kidneys cause? |
|
Definition
| 25-hydroxycholecalciferol-1-alpha-hydroxylase expression to make 1,25-dihydroxyvitamin D3 |
|
|
Term
| What effect does 1,25 dihydroxyvitamin D3 have on 25-hydroxycholecalciferol-1-alpha-hydroxylase? |
|
Definition
|
|
Term
| What is the purpose of CYP24A1? |
|
Definition
| Metabolizes 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 into 24,25-dihydroxyvitamin D3 and 1,24,25-trihydroxyvitamin D3 |
|
|
Term
| What is the plasma ratio of [25-hydroxyvitamin D3]/[24,25-dihydroxyvitaminD3] useful for? |
|
Definition
| Marker for Vitamin D metabolism dysregulation in relationship to plasma calcium levels |
|
|
Term
| How does CYP24A1 regulate the amount of biologically active vitamin D3 in the body? |
|
Definition
| Its products are excreted in the urine and feces |
|
|
Term
| How is Vitamin D2 different from D3? |
|
Definition
The binding affinity for D3 for the VDR is much higher than for D2.
Vitamin D2 is not the preferred substrate of 25 |
|
|
Term
| Where are all the actions of Vitamin D mediated through? |
|
Definition
|
|
Term
| What does 1,25-dihydroxyvitamin D3 binding to VDR cause? |
|
Definition
| cascade of molecular interactions |
|
|
Term
| What is the purpose of TRPV6? |
|
Definition
It functions as a Ca2+ channel that is expressed in the brush border membrane.
Mediates the first step of trans-epithelial Ca2+ absorption |
|
|
Term
| What is the purpose of Calbindin? |
|
Definition
| Functions as a cytosolic Ca2+ transporter that facilitates the transport of intracellular Ca2+ to the basolateral membrane via Ca2+ATPase and Na/Ca Exchanger |
|
|
Term
| Why are obese people more likely to have Vitamin D deficiency? |
|
Definition
|
|
Term
| Why is 25-hydroxy Vit D3 used to trace Vitamin D levels in the blood? |
|
Definition
| 1,25 dihydroxy Vitamin D3 has a very short half life (3 hours) |
|
|
Term
| How does PTH affect the Kidney, Bone, and Small Intestines? |
|
Definition
Kidney: 1-alpha-hydroxylase causes increased 1,25 dihydroxy D3 , Ca2+ reabsorption, and phosphate excretion
Bone: Osteoclasts stimulation and Ca2+/P release
Small Intestines: Ca2+ absorption/transport protein promotion and Ca2+/Phosphorus absorption |
|
|
Term
|
Definition
| Vitamin D3 deficiency causing decreased ability of small intestines to absorb Ca2+ |
|
|
Term
| What causes osteomalacia? |
|
Definition
| Vitamin D3 deficiency in adults that leads to demineralization of bones and reduced bone strength. |
|
|
Term
|
Definition
Water-soluble particles that serve to transport lipids in the blood circulation.
|
|
|
Term
| What are lipoproteins composed of? |
|
Definition
Monolayer of phospholipids
Apolipoproteins (Apos) anchored in monolayer
Hydrophobic interior space |
|
|
Term
| What are the types of lipoprotein? |
|
Definition
| HDL, IDL, LDL, VLDL, Chylomicron, Chylomicron Remnant |
|
|
Term
| What lipoprotein has the highest percent of cholesterol content? |
|
Definition
|
|
Term
| What lipoprotein collects unwanted cholesterol molecules from peripheral tissues and brings them to the liver for disposal? |
|
Definition
|
|
Term
| What are Chylomicrons and VLDL dependent on? |
|
Definition
Chylomicron: ApoB48
VLDL: ApoB100 |
|
|
Term
| What transports lipids to the rest of the body? |
|
Definition
|
|
Term
| What are lipoproteins that contain ApoB or ApoA called? |
|
Definition
ApoB: Beta-apolipoproteins
ApoA: Alpha-apolipoproteins |
|
|
Term
| What is Hyper-beta-lipoproteinemia? |
|
Definition
Higher than normal plasma LDL levels |
|
|
Term
| What is Dysbetalipoproteinemia? |
|
Definition
| High levels of plasma chylomicron remnant (chylomicron remnant removal disease) |
|
|
Term
| What is Abetalipoproteinemia? |
|
Definition
| Caused by abnormally low plasma levels of ApoB-containing chylomicron and VLDL due to synthesis and or secretion defects. |
|
|
Term
|
Definition
| A molecule of glycerol esterfied with three fatty acids. |
|
|
Term
| What is the bulk of fat in a fatty meal composed of? |
|
Definition
|
|
Term
| What is needed to be secreted in order to digest dietary triglycerides? |
|
Definition
Gallbladder: Bile Salts
Pancreas: Bicarbonate, colipase, and lipases |
|
|
Term
| What does Cholecystokinin stimulate? |
|
Definition
| Secretion of pancreatic colipase, lipases, and bile salts |
|
|
Term
| What does secretin stimulate? |
|
Definition
|
|
Term
| What is the purpose of bicarbonate? |
|
Definition
| To keep the pH near neutral so that lipase can be active |
|
|
Term
| How does pancreatic lipase affect fat digestion? |
|
Definition
| It removes fatty acyl groups from carbons-1 and 3 and produces a mixture of 2-monoacylglycerol and free fatty acids. |
|
|
Term
| How does cholesteryl esterase affect cholesteryl esters? |
|
Definition
| It hydrolyzes them to produce cholesterol and free fatty acids. |
|
|
Term
| How are cholesterol molecules absorbed by enterocytes in the small intestine? |
|
Definition
| They bind to the NPC1L1 protein |
|
|
Term
| How can NPC1L1 affect cholesterol blood levels? |
|
Definition
| Blocking NPC1L1 can prevent cholesterol absorption, thus leading to overall lower cholesterol levels. |
|
|
Term
| How are bile salts absorbed by the Small Intestine and the Liver? |
|
Definition
Small intestine: Binds to ASBT
Liver: Binds to OSTalpha-OSTbeta |
|
|
Term
| What causes lipid malabsorption? |
|
Definition
| Cystic Fibrosis, Bile Salt deficiency, pancreatic cancer, pancreatic lipase/colipase deficiency, and shortened bowel. |
|
|
Term
| What are the results of lipid malabsorption? |
|
Definition
| Increased lipid excretion in the stool and reduced absorption of fat-soluble vitamins and deficiency of dietary essential long-chain fatty acids. |
|
|
Term
| Which layer of the lipoprotein makes it water soluble? |
|
Definition
| The monolayer of phospholipids. |
|
|
Term
| What is the cholesterol ratio? |
|
Definition
Total cholesterol: HDL cholesterol ratio.
(4:1 ratio or less is optimal) |
|
|
Term
| What type of apolipoprotein is HDL? |
|
Definition
|
|
Term
| What type of apolipoprotein is LDL? |
|
Definition
|
|
Term
| What are the locations of Chylomicron and VLDL synthesis? |
|
Definition
Chylomicrons: Entrerocyte
VLDL: Hepatocytes |
|
|
Term
| What Apoprotein does Chylomicron and VLDL require? |
|
Definition
Chylomicron: ApoB48
VLDL: ApoB100 |
|
|
Term
| What do chylomicrons and VLDL carry? |
|
Definition
Chylomicrons: Dietary Fat and fat soluble vitamins (A,D,E,K)
VLDL: cholesterol, triglyceride, and fat-soluble molecules from the liver |
|
|
Term
| Why does ApoB48 contain only 48% of the MW of ApoB100? |
|
Definition
| At 2153 CAA change to UAA, a stop codon. |
|
|
Term
| What happens if SAR1B is defective in Small Intestine Enterocytes? |
|
Definition
| Chylomicron Retention Disease due to accumulation of chylomicrons in the cells. |
|
|
Term
| How does ApoB48 synthesize chylomicron particles in the ER of small intestine enterocytes? |
|
Definition
|
|
Term
| How are chylomicrons secreted from small intestine enterocyte Golgi? |
|
Definition
| SAR1B dependent mechanism into the lymphatic system |
|
|
Term
| How does ApoB100 synthesize nascent VLDL particles in the ER of hepatocytes? |
|
Definition
| MTP-dependent mechanism using |
|
|
Term
| What causes Abetalipopoteinemia (Bassen-Kornzweig Syndrome)? |
|
Definition
| Loss-of-function mutations in the MTP gene causing improper packaging and secretion of apolipoprotein B-containing lipoproteins (chylomicrons and VLDL loss) |
|
|
Term
| What results from Abetalipopoteinemia? |
|
Definition
Fatmalabsorption, and fatty, foul-smelling stool (steatorrhea).
Hypocholesterolemia.
Deficiency of fat-soluble vitamins.
Star-shaped RBCs (acanthocytosis) |
|
|
Term
| What are the signs and symptoms of Chylomicron Retention Disease (Anderson's Disease)? |
|
Definition
| Failure to thrive, diarrhea, steatorrhea, and white duodenal mucosa. |
|
|
Term
| What are dietary essential long-chain fatty acids essential for the synthesis of? |
|
Definition
| Prostaglandins, leukotrienes, and thromboxanes |
|
|
Term
| What is the purpose of ApoCII in chylomicrons and VLDL? |
|
Definition
| ApoCII recognizes and binds to LPL to cause a conformational change that activates it. |
|
|
Term
| Where does the maturation of the chylomicron and VLDL occur? |
|
Definition
| Bloood of the circulatory system |
|
|
Term
| Where is LDL found and what is it dependent on? |
|
Definition
Capillaries of peripheral tissues.
Dependent on Insulin |
|
|
Term
| How are absorbed fatty acids used in muscle and adipocytes? |
|
Definition
Muscle: Metabolized for E production
Adipocytes: used to synthesize triglyceride to store E |
|
|
Term
| After LPL is activated, what happens to the chylomicrons and VLDL? |
|
Definition
| Free fatty acids are absorbed by cells surrounding and glycerol is transported to the liver for gluconeogenesis, E production, or resynthesis of triglyceride. |
|
|
Term
| What happens to to Chylomicrons and VLDL after they are metabolized in the blood? |
|
Definition
Chylomicron: Chylomicron remnant
VLDL: LDL
Both are enriched in cholesterol. |
|
|
Term
| What cells express a high level of VLDL receptor? |
|
Definition
| Cells that metabolize a large amount of fatty acids (Cardiac muscle, skeletal muscle, adipocytes) |
|
|
Term
| What does VLDLR bind to in order to internalize it? |
|
Definition
| ApoE found on VLDL and IDL |
|
|
Term
| What does LDLR bind to in order to internalize it? |
|
Definition
|
|
Term
| Why can LDL not be reabsorbed by VLDLR? |
|
Definition
| Metabolism of IDL to LDL removes the ApoE |
|
|
Term
| Do chylomicrons contain ApoE? |
|
Definition
|
|
Term
| Why do chylomicrons not interact with VLDLR? |
|
Definition
| Steric Hindrance (they have ApoE!) |
|
|
Term
| What causes Type III Hyperlipoproteinemia (Familial dysbetalipoproteinemia)? |
|
Definition
| Inability of the liver to internalize chylomicron remnants due to mutations in ApoE |
|
|
Term
| What does failure to internalize chylomicron remants due to ApoE mutation cause? |
|
Definition
| Increased cholesterol level in the plasma |
|
|
Term
| What receptors can Chylomicron remnants utilize to internalize into the liver? |
|
Definition
|
|
Term
| How is VLDL vs Chylomicrons released into the blood? |
|
Definition
Chylomicrons go into the lymphatics first via SAR1B, then into the blood.
VLDL is exocytosed straight into the blood.xd |
|
|
Term
| What are the supernatant and particulate fractions? |
|
Definition
Supernatant: Liquid Phase
Particulate: Packed Phase |
|
|
Term
| What is the formula for Hct? |
|
Definition
| Hct = (Volume- packed cells)/ (Volume - Total Blood) x 100 |
|
|
Term
| What is the normal range of Hct? |
|
Definition
|
|
Term
| What is high levels of hematocrit and low levels of hematocrit? |
|
Definition
High: Polycythemia
Low: Anemia |
|
|
Term
| What do you get in the supernatant when you centrifuge blood without anitcoagulant? |
|
Definition
|
|
Term
| What do you get in the supernatant when you centrifuge blood with anitcoagulant? |
|
Definition
|
|
Term
| What is the main difference between serum and plasma? |
|
Definition
| Plasma has clotting factors, serum does not. |
|
|
Term
|
Definition
| The WBCs and platelets sitting on top of the RBCs in the particulate fraction. |
|
|
Term
| What is the mean corpuscular volume (MCV)? |
|
Definition
| The amount of volume an RBC can hold (87 microns) |
|
|
Term
| Why is the biconcave shape of the RBC important? |
|
Definition
| The shape gives it about 50% more surface area than the same volume as a sphere. |
|
|
Term
| What is the Mean Corpuscular Hemoglobin Concentration (MCHC)? |
|
Definition
| The percentage of hemoglobin per RBC |
|
|
Term
| What is the Mean Corpuscular Hemoglobin (MCH)? |
|
Definition
| The dry weight of hemoglobin per RBC |
|
|
Term
| What enzyme catalyzes the dissociation of Carbonic acid into CO2 and H2O? |
|
Definition
|
|
Term
| What is normacytic normachromic anemia? |
|
Definition
| RBCs are normal size and contain normal amounts of hemoglobin, but there are fewer cells. |
|
|
Term
| What is microcytic hypochromic anemia? |
|
Definition
| Fewer RBCs, that are paler, and smaller. |
|
|
Term
| What is macrocytic normachromic anemia? |
|
Definition
| Fewer RBCs, that are larger cells. |
|
|
Term
| What state must the Fe in the Hemoglobin maintain in order to stay active? |
|
Definition
|
|
Term
| What happens when the Oxygen in Hemoglobin is reduced to superoxide anion? |
|
Definition
1. Met-Hgb cannot bind to O2
2. Superoxide ion is extremely reactive |
|
|
Term
| How is Met-Hgb reversed to Hgb? |
|
Definition
| Met-Hgb reductase using cyt b5 (Fe2+) |
|
|
Term
| How is cyt b5 (Fe3+) converted back to cyt b5 (Fe2+)? |
|
Definition
| Using Cyt B5 reductase with NADH as the reducing agent. |
|
|
Term
| How is the superoxide anion removed from the system? |
|
Definition
Two are converted - one reduced and one is oxidized with dismutase.
2O2-=> O2+H2O2
H2O2 is broken down with catalase to 2H2O+2O2 |
|
|
Term
| What happens when membranes are oxidized? |
|
Definition
| The double bonds of the FAs are attacked, forming peroxides, which form free radicals. |
|
|
Term
| What are the ways to prevent membranes from oxidation? |
|
Definition
| Vitamin E and Glutathione |
|
|
Term
| What are the types of Vitamin E in the body? |
|
Definition
| Tocopherols and tocotrinols (alpha-tocopherol is most common) |
|
|
Term
| What reduces the oxidized forms of Vitamin E? |
|
Definition
| ascorbate and glutathione |
|
|
Term
| What is glutathione peroxidase? |
|
Definition
| Selenoenzyme which catalyzes the reduction of various peroxides to their alcohol with glutathione as the reducing agent. |
|
|
Term
| What is glutathione reductase? |
|
Definition
| Flavoprotein that catalyzes the reduction of oxidized glutathione to reduced form using NADH |
|
|
Term
| What is the method of energy production for RBCs? |
|
Definition
|
|
Term
| What happens if NADH is not needed in the RBC? |
|
Definition
| It is converted to NAD+ by LDH |
|
|
Term
| Where is the NADPH for glutathione reductase supplied from? |
|
Definition
|
|
Term
| What controls the synthesis and breakdown of 2,3 BPG? |
|
Definition
|
|
Term
| How does 2,3 BPG affect hemoglobin? |
|
Definition
| It's an allosteric modulator so it regulates the transport of Oxygen by decreasing hemoglobin's affinity for it and promoting the release of O2 from oxy-hemoglobin. |
|
|
Term
| Why is hemolytic anemia damaging to the kidney? |
|
Definition
| Hemoglobin is at the upper limit of the kidney's filtering ability, which causes damage. |
|
|
Term
| What does Haptoglobin do? |
|
Definition
| It binds to free hemoglobin in the blood to form a large comlpex that cannot be filtered by the kidney, which is cleared by the reticuloendothelial system. |
|
|
Term
|
Definition
| It binds to free heme in circulation that prevents the loss of heme (and iron) via the kidney. Heme is catabolized into bilirubin and iron. |
|
|
Term
| What will a defect in G6PDH cause? |
|
Definition
| If an oxidant is introduced, then your cells won't be able to reduce it and they will lyse. |
|
|
Term
| What will a defect in PK cause in your RBCs? |
|
Definition
| You won't be able to produce ATP from Pyruvate, so Na/K translocase won't have any activity. |
|
|
Term
| When does hemoglobin synthesis begin and end? |
|
Definition
Begins: Early Normoblast Stage
Ends: Reticulocyte Stage |
|
|
Term
| How long does erythropoiesis require? |
|
Definition
|
|
Term
| What major events must occur during erythropoiesis? |
|
Definition
| DNA synthesis and protein biosynthesis (especially hemoglobin) |
|
|
Term
| What is the starting compound of the biosynthesis of ribonucleotides and how does it occur? |
|
Definition
| PRPP from R5P via PRPP Synthetase |
|
|
Term
| What is the major control point for purine and pyrimidine synthesis? |
|
Definition
|
|
Term
| What is the end point of the PRPP pathway? |
|
Definition
|
|
Term
| What donates the Nitrogen and the Carbons of the IMP ring? |
|
Definition
N: glycine, aspartate, 2 glutamine
C: 2 glycine, CO2, 2 folate |
|
|
Term
| What converts GMP and AMP into dinucleotides (GTP, ATP)? |
|
Definition
|
|
Term
| How does GDP and ADP get converted to GTP and ATP? |
|
Definition
GDP: Dinucleotide kinase
ADP: OxPhos |
|
|
Term
| What products are needed for Pyrimidine Nucleotide Synthesis? |
|
Definition
| Carbamoyl phosphate (CP) and aspartate |
|
|
Term
| What converts UMP to UDP and UTP? |
|
Definition
| UMP kinase and dinucleotide kinase |
|
|
Term
| What converts UTP to CTP? |
|
Definition
|
|
Term
| What is the reducing agent for deoxynucleotide synthesis? |
|
Definition
|
|
Term
| Where are the C1 pieces needed for purine and pyrimidine synthesis donated from? |
|
Definition
|
|
Term
| What are the three parts of Folic Acid? |
|
Definition
| Pteridine Ring, Para-aminobenzoic acid (PABA), and glutamic acid |
|
|
Term
| How is FH4 formed from Folate? |
|
Definition
| Reduction of 5-6 and 7-8 double bonds |
|
|
Term
| What enzyme catalyzes the reduction of folate to FH4? |
|
Definition
| FH2 reductase in two steps. |
|
|
Term
| Where can formic acid, formaldehyde, and methanol be bound to on FH4? |
|
Definition
| N5, N10, or both positions |
|
|
Term
| What are the adducts at the oxidation state for formic acid? |
|
Definition
N10 formyl-FH4
N5,10 methenyl-FH4
N5 formimino-FH4 |
|
|
Term
| What are the adducts at the oxidation state for formaldehyde? |
|
Definition
|
|
Term
| What are the adducts at the oxidation state for methanol? |
|
Definition
|
|
Term
| What makes up the folate pool? |
|
Definition
| five C1-FH4 compounds, plus FH4 |
|
|
Term
| What is the major donor of one carbons to the folate pool? |
|
Definition
|
|
Term
| How is the one carbon donated from serine to glycine? |
|
Definition
| Hydroxymethyl transferase with PLP converts serine to glycine |
|
|
Term
| How does Histidine donate N5 forminino FH4? |
|
Definition
| It is converted from N-forminino glutamate (FIGLU) to glutamate via Transferase |
|
|
Term
| What is the major methylating agent in the body? |
|
Definition
|
|
Term
| How is homocysteine generated? |
|
Definition
| The methyl group of S-AM is donated to an acceptor molecule creating homocysteine |
|
|
Term
| How is methionine regenerated? |
|
Definition
| Homocysteine is converted via B12dependent methyltransferase |
|
|
Term
|
Definition
| The hydroxymethyl group of N5,10 methylene FH4 is transferred to dUMP via TMP synthase |
|
|
Term
| What are the vitamin and coenzyme forms of B12? |
|
Definition
Vitamin: Vitamin B12 (CN) and B12a (OH)
Coenzyme: methyl B12 (CH3) and Ad-B12 (5-deoxyadenosyl) |
|
|
Term
| What are the two B12-dependent reactions that occur in the body (there's a third we don't care about)? |
|
Definition
Homocysteine N5-methyl-FH4 methyl transferase
Methyl-malonyl-CoA mutase |
|
|
Term
| How will B12 deficiency affect the folate pool? |
|
Definition
| Methyltransferase activity will be reduced, causing a secondary folate deficiency. |
|
|
Term
| What is the purpose of cobalophilin (CP) and where is it found? |
|
Definition
| Binds free B12. Found in the saliva. |
|
|
Term
| What secretes Intrinsic Factor? |
|
Definition
|
|
Term
| What causes the release of B12 and where does it occur? |
|
Definition
| Trypsin digesting CP in the upper GI. |
|
|
Term
| After trypsin digests CP, where does B12 bind? |
|
Definition
|
|
Term
|
Definition
| In the Ileum via IF-B12 receptors. |
|
|
Term
| What does B12 bind to after it is absorbed in the Ileum? |
|
Definition
|
|
Term
| How is B12 uptaken by the cells? |
|
Definition
| The cells contain TCII-B12 receptors |
|
|
Term
| What happens if DNA synthesis replication machinery or substrates are impaired or defective? |
|
Definition
| Cell replication is impaired. |
|
|
Term
| What phase will the cell be stuck in if synthesis is impaired? |
|
Definition
|
|
Term
| How will macrocytic anemia affect total Hmg, Hct, MCV, and MCHC? |
|
Definition
Hmg Concentration, Hct: Decreased
MCV: increased
MCHC: normal range |
|
|
Term
| How do you get hemoglobin formation? |
|
Definition
| Heme combination with alpha beta chains |
|
|
Term
| What is used to form heme? |
|
Definition
| protoporphyrin IX and Fe2+ using ferrochelatase |
|
|
Term
| How is Uroporphyrinogen III formed? |
|
Definition
| Succinyl-CoA+glycine->5 ALAx2 -> Porphobilogen x4 -> uroporphyrinogen III |
|
|
Term
| What happens in Uroporphyrinogen III if cosynthase is absent? |
|
Definition
| URO-I is formed (Dead end) |
|
|
Term
|
Definition
| Large protein where ferric ions are stored as iron oxide. |
|
|
Term
|
Definition
| Glycoprotein with two high affinity binding sites for ferric ions that transports iron in the blood to various tissues in the body. |
|
|
Term
| What is brush border ferrireductase? |
|
Definition
| Brush border enzyme that reduces dietary ferric ions to ferrous ions. |
|
|
Term
| How are ferric ion reduced to ferrous ions non-enzymatically? |
|
Definition
|
|
Term
| What is the divalent metal ion transporter 1 (DMT1)? |
|
Definition
| A transporter for divalent cations (Fe, Mn, Co, Zc, Cu) that is found on the apical side of enterocytes of the proximal duodenal. |
|
|
Term
|
Definition
| Ferrous ion transporter in the basolateral membrane that transfers ferrous ions across into the blood. |
|
|
Term
|
Definition
| Basolateral membrane enzyme that contains copper and is similar to cerruloplasmin in that is has ferroxidase activity. |
|
|
Term
|
Definition
| A peptide that helps regulate iron uptake in the intestine and release of iron from macrophages. |
|
|
Term
| What occurs if plasma level of iron is increased? |
|
Definition
| Synthesis of hepcidin increases (decreases absorption of dietary iron) |
|
|
Term
| How does hepcidin affect ferroportin? |
|
Definition
| It is a negative regulator (binds to it to internalize and degrade it) |
|
|
Term
| How are intracellular iron levels controlled? |
|
Definition
| At the level of Tf Receptor and ferritin |
|
|
Term
| What happens when there are high cellular levels of Iron? |
|
Definition
| Synthesis of Tf-Receptor is down regulated and Ferritin is upregulated. |
|
|
Term
| What occurs when there is interference with protein or heme biosynthesis? |
|
Definition
|
|
Term
| What are Lipoprotein Lipase Deficiencies associated with? |
|
Definition
| Grossly elevated serum triglyceride levels. |
|
|
Term
| Why is Chylomicron levels elevated in LPL deficiency, yet VLDL levels are not? |
|
Definition
| VLDL can be uptaken by VLDLR, but Chylomicrons cannot. |
|
|
Term
| Chylomicronemia is a result of what type of deficiency? |
|
Definition
|
|
Term
| What is Type 1a and type 1b hyperlipoproteinemia? |
|
Definition
1a: LPL deficiency
1b: ApoCII deficiency |
|
|
Term
| What is the theory as to why pancreatitis is causes by LPL deficiency? |
|
Definition
| Large chylomicrons aggregate and impair blood flow, causing systemic inflammation to develop. |
|
|
Term
| What symptoms are used to diagnose LPL deficiency? |
|
Definition
Severy hypertriglyceridemia
Episodic Abdominal pain
Recurrent acute pancreatitis
Xanthomata
Hepatosplenomegaly |
|
|
Term
| What causes the lactescent appearance of blood in LPLD? |
|
Definition
|
|
Term
| What is the absence of LPL enzyme activity in post-heparin plasma diagnostic of? |
|
Definition
|
|
Term
| What is Type IV and Type V VLDL Metabolism Disease? |
|
Definition
Type IV: Overproduction of VLDL and impaired VLDL metabolism.
Type V: Increased production or decreased clearance of VLDL and chylomicron |
|
|
Term
| What is the function of LDL? |
|
Definition
| It provides cholesterol to any cell types that have a need for it and contain LDLR. |
|
|
Term
| Who is resposible for the clearance of excessive LDL from the blood? |
|
Definition
| Hepatocytes using LDLR-mediated internalization |
|
|
Term
| What are the causes of Type II Hyperlipoproteinemia? |
|
Definition
1. Loss of function of LDLR
2. Loss of function of ApoB (mutant ApoB100)
3. Gain of function of PCSK9 gene that increases degradation of LDLR. |
|
|
Term
| What is reverse cholesterol transport? |
|
Definition
| The process by which HDL acts to move cholesterol from the peripheral tissues back to the liver |
|
|
Term
| How are excessive cholesterol molecules pumped out of the non-hepatic peripheral cells? |
|
Definition
|
|
Term
|
Definition
| The enzyme that esterfies cholesterol molecules into cholesterol esters. |
|
|
Term
| What does HDL use to extract phospholipid from VLDL, LDL, chylomicron to increase the surface area of the phospholipid shell? |
|
Definition
| PLTP (Phospholipid Transfer Protein) |
|
|
Term
| What is CETP (Cholesterol Ester Transfer Protein)? |
|
Definition
| Protein used by HDL to transfer some of its cholesteryl ester to ApoB lipoproteins and acquire some TG and phospholipids |
|
|
Term
| What is SR-B1 (scavenger receptor class B type 1)? |
|
Definition
| Receptor in the plasma membrane of cells that is used to siphon cholesteryl ester from HDL |
|
|
Term
| What causes the problems associated with LCAT deficiencies? |
|
Definition
| accumulation of free cholesterol in the cornea and kidney |
|
|
Term
| What causes Tangier's Disease, and what are the characteristics? |
|
Definition
| ABCA1 deficiency - low plasma HDL levels and accumulation of cholesterol inside cells in many tissues |
|
|
Term
| What transfer system is affected in Tangier's Disease? |
|
Definition
| The transfer of unwanted cholesterol in peripheral cells to HDL |
|
|
Term
| How does too much PCSK9 activation affect cholesterol levels? |
|
Definition
| Hypercholesterolemia due to high LDL levels |
|
|
Term
| What are the fat-soluble vitamins? |
|
Definition
| Vitamin A1 (retinol), D2, E, K |
|
|
Term
| What are the water soluble vitamins? |
|
Definition
| Thiamine, Riboflavin, Niacin, patothetnic acid, B6, biotin, folic acid, B12, Vitamin C |
|
|
Term
| How are water soluble vitamins absorbed? |
|
Definition
| Specific transporters in the apical membrane of intestinal cells and exported to basolateral side. |
|
|
Term
| How are fat soluble vitamins absorbed? |
|
Definition
| Packaged into micelles and used to synthesize chylomicrons (into lymphoid, then into the blood). |
|
|
Term
|
Definition
| Biotin with a lysine residue. Acts as a coezyme. |
|
|
Term
| Where does biotin acts as a coenzyme? |
|
Definition
Pyruvate carboxylase
Acetyl-CoA carboxylase
Propionyl-CoA carboxylase |
|
|
Term
|
Definition
| A protein that binds to biotin and reduces its bioavailability. |
|
|
Term
| What is the most abundant form of pantothenic acid in the body? |
|
Definition
|
|
Term
| What part of Coenzyme A allows it to be used in acyl transfer reaction or by fatty acid synthase? |
|
Definition
|
|
Term
| What complexes are lipoic acid useful for? |
|
Definition
Pyruvate dehydrogenase complex.
alpha-Ketoglutarate dehydrogenase complex.
Branched-chain alpha-ketoacid dehydrogenase complex.
Glycine Cleavage Enzyme complex. |
|
|
Term
| How does heavy metal toxicity affect lipoic acid? |
|
Definition
| Heavy metals have a high affinity for the thiol groups in reduced form, so there is a reduced activity of mitochondrial lipoic acid-dependent enzymes causing less ATP production. |
|
|
Term
| Why do the signs of thiamin deficiency appear so quickly? |
|
Definition
| There are no sources of storage in the human body. |
|
|
Term
| Where is Thiamin Pyrophosphate (TPP) used as a coenzyme? |
|
Definition
Pyruvate Dehydrogenase
alpha-ketoglutarate dehydrogenase
Transketolase
Branched-chain alpha-ketoacid dehydrogenase |
|
|
Term
|
Definition
| Phosphate donor for phosphorylation. |
|
|
Term
| What energy production system is affected by Thiamin deficiency? |
|
Definition
| Aeorbic energy production |
|
|
Term
| What will a deficiency of PDH and alpha-KGDH cause? |
|
Definition
| Reduced ATP production from glycolysis and TCA |
|
|
Term
| How does PDH deficinecy affect neurotransmitter functioning? |
|
Definition
| acetylcholine and myelin production are PDH driven. |
|
|
Term
| How does alpha-KGDH deficiency affect the neurosystem? |
|
Definition
| Alpha-KGDH help maintain glutamate levels, which is used for GABA and aspartate synthesis., |
|
|
Term
| What products is Transketolase responsible for? |
|
Definition
| NADPH and Ribose-5-phosphate |
|
|
Term
| What enzyme is most sensitive to thiamin deficiency? |
|
Definition
|
|
Term
| What is the only thiamin dependent enzyme that RBCs contain? |
|
Definition
|
|
Term
| What deficiency causes Beri beri? |
|
Definition
|
|
Term
|
Definition
| Functional deficits of the Nervous System due to thiamin deficiency without edema of CV failure. |
|
|
Term
|
Definition
| Funcitonal deficit of the CV system due to thiamin deficiency marked by edema due to renin-angiotensin hyperactivity. |
|
|
Term
| What is Shoshin beriberi? |
|
Definition
| More rapid form of wet beriberi with predominant damage to the heart in the absence of edema. Infants can develop if breastfeeding from thiamin deficient mothers. |
|
|
Term
| What thiamin deficiency disease will chronic alcoholism lead to? |
|
Definition
| Wernicke-Korsakoff Syndrome (WKS) |
|
|
Term
| What are the two components of WKS? |
|
Definition
| Wernicke's encephalopathy (acute) and Korsakoff's psychosis (long-lasting) |
|
|
Term
| How does alcoholism affect thiamin levels? |
|
Definition
Decreased absorption due to GI damage.
Increased loss due to diarrhea.
Inhibition of thiamine pyrophosphokinase. |
|
|
Term
|
Definition
| Enzymes that utilize flavocoenzyme |
|
|
Term
| What are the two flavocoenzymes that are synthesized using riboflavin? |
|
Definition
|
|
Term
| What is the role of FAD as a coenzyme? |
|
Definition
| Acyl-CoA dehydrogenase and beta-oxidation of fatty acids. |
|
|
Term
| What reactions are FAD and FMN involved in and how do they function? |
|
Definition
| They function as electron acceptors and donors and they are involved in oxidation-reduction reactions. |
|
|
Term
| Where are flavoproteins functioning in the ETC? |
|
Definition
|
|
Term
| What will riboflavin deficiency cause? |
|
Definition
Impaired E production from fatty acids.
Decreased Glutathione reductase => increased oxidative activities
Decreased Xanthine Oxidase => reduced blood uric acid levels, increased oxidative activities
|
|
|
Term
| What causes congenital riboflavin deficiency? |
|
Definition
| Riboflavin transporter gene mutation. |
|
|
Term
| What would be symptoms of mild riboflavin deficiency? |
|
Definition
Lesions of the skin, especially in the corners of the mouth, with a rare, swollen tongue.
|
|
|
Term
| What would be symptoms of severe riboflavin deficiency? |
|
Definition
| Hypotonia, ataxia, dysphagia, muscle weakness and progressive muscle paralysis, and bilateral sensoineural hearing loss. |
|
|
Term
| What will mutations in RFVT cause? |
|
Definition
| Riboflavin deficiency and BVVL/FL syndrome. |
|
|
Term
| What is Bron-Vialetto-Van-Laere (BVVL) and Fazio-Londe (FL) Syndrome? |
|
Definition
| Neurological disorder caused by riboflavin deficiency leading to paralysis of the diaphragm, deterioration with hypotonia, respiratory insufficiency, progressive pontobulbar palsy, etc. |
|
|
Term
| Elevation and accumulation of what acts as a diagnostic marker for ACADs? |
|
Definition
|
|
Term
| What tests can be done to assess riboflavin deficiency? |
|
Definition
| RBC riboflavin and glutathione reductase. |
|
|
Term
| What proteins are made using Niacin? |
|
Definition
|
|
Term
| What are sirtuins (SIRT1, SIRT17)? |
|
Definition
| NAD+-dependent protein deacetylases and/or ADP-ribosyltransferases. They are key metabolic sensors. |
|
|
Term
| What areas of DNA Damage repair is NAD+ needed? |
|
Definition
| PARP-mediated DNA damage repair |
|
|
Term
|
Definition
| An enzyme that detects and signals DNA damage to repair mechanisms in response to single strand DNA breaks. |
|
|
Term
| What is used for de novo synthesis of niacin? |
|
Definition
|
|
Term
| How do isoniazid drugs cause niacin deficiency? |
|
Definition
| They inhibit Kinurenin aminotransferase, a key enzyme for de novo synthesis of niacin from tryptophan |
|
|
Term
| What is the most common disorder caused by niacin deficiency? |
|
Definition
|
|
Term
| What are the symptoms of Pellegra? |
|
Definition
| Three Ds: Dermatitis, diarrhea, dementia |
|
|
Term
| Why does symptoms of pellegra develop from Hartnup's disease? |
|
Definition
| Renal reabsorption of neutral amino acids (namely tryptophan and histidine) is inhibitied. |
|
|
Term
| What will high intakes of nicotonic acid cause? |
|
Definition
| Hot flushing syndromes due to cutaneous vasodilation of the face, neck, and torso. |
|
|
Term
| What are Type A and Type B Lactic Acidosis? |
|
Definition
Type A: Acidosis due to inadequate tissue oxygen delivery
Type B: Acidosis with no connection to clinical reduction in oxygen delivery. |
|
|
Term
| What are Type B1, B2, and B3 lactic acidosis? |
|
Definition
B1: associated with underlying disease
B2: associated with drugs and toxins
B3: associated with inborn errors in metabolism
|
|
|
Term
| How does vitamin C protect proteins, lipids, carbohydrates, and nucleic acids from damage? |
|
Definition
| It has antioxidant properties. |
|
|
Term
| What effects does vitamin A have on vitamin E? |
|
Definition
| It restores its antioxidant properties by turning it from its oxidized form to its reduced form. |
|
|
Term
| How does vitamin facilitate Fe absorption? |
|
Definition
| It reduces it from ferric form (Fe3+) to ferrous form (Fe2+), so it can be absorbed by DMT1 |
|
|
Term
| Why is vitamin C required for development and maintenance of scar tissue, blood vessels, and cartilage? |
|
Definition
| It is required for prolyl hydroxase and lysyl hydroxylase |
|
|
Term
| Why is vitamin C needed for collagen maintenace? |
|
Definition
| Prolyl hydroxylase uses Vitamin C to keep iron in the ferrous state |
|
|
Term
| How is Vitamin C needed for norepinephrine/epinephrine synthesis? |
|
Definition
| Dopamine beta-hydroxylase uses Cu as a prosthetic factor, and vitamin C is needed to keep Cu in the reduced Cu+ state. |
|
|
Term
| How is vitamin C needed for carnitine biosynthesis? |
|
Definition
| Two of the steps require Vitamin C |
|
|
Term
| What are the symptoms of scurvy? |
|
Definition
| Furst malaise and lethargy, then muscle pain (myalgia), easy brusing, loss of teeth, pale skin, etc. |
|
|
Term
| How does Carcinoid syndrome affect Niacin levels? |
|
Definition
| Increased production of serotonin from tryptophan leads to niacin deficiency. |
|
|
Term
| What are the forms of vitamin A? |
|
Definition
Retinol
Retinal
Retinoic acid |
|
|
Term
| What structure is necessary for the activity of vitamin A? |
|
Definition
| Beta-ionone ring with an isoprenoid chain attached |
|
|
Term
| Why is retinol, but not retonoic acid, used to treat vitamin A deficiency? |
|
Definition
Retinol and Retinal are interconvertible.
Retinal can be converted to retonoic acid, but retinoic acid cannot be converted back to retinal. |
|
|
Term
| The synthesis of retinol-binding protein in the liver is dependent on what? |
|
Definition
|
|
Term
| How will deficiency of retinal affect vision? |
|
Definition
| It will cause night blindness due to loss of 11 cis-retinal |
|
|
Term
| How does retinoic acid affect gene expression? |
|
Definition
| It binds to RAR, forming a RA-RAR complex, which activates retinoid acid-specific genes. |
|
|
Term
| How does retinoic acid deficiency affect the epithelium? |
|
Definition
| Epithelial cells require retinoic acid for differentiation primarily by the ability to activate RA-RAR dependent genes. |
|
|
Term
| Why does Vitamin A deficiency affect mucous secretion? |
|
Definition
1. Reduced sulphotransferases synthesis needed for GAG synthesis.
2. Mucous-secreting epithelium replaced by keratin-producing epithelium |
|
|
Term
| How is STRA6 involved in vitamin A uptake? |
|
Definition
| STRA6 is involved in Retinol uptake from RBP in the circulation. |
|
|
Term
| What will deficient SRA6 cause? |
|
Definition
| Anopthalmia (no eyes), microphthalmia, pulmonary agenesis, duodenal stenosis, pancreatic malformations, intrauterine growth retardation. |
|
|
Term
| What is Xerothalmia, and what causes it? |
|
Definition
Dryness of the cornea with progessive deterioration.
Caused by lack of retinoic acid. |
|
|
Term
| What is rhodoposin and what will a deficiency cause? |
|
Definition
Area of the membrane disc in rods and cones that contain 11-cis-retinal and opsin.
Deficiency of 11-cis-retinal causes night blindness. |
|
|
Term
| How does treatment of all-trans retinoic acid (ATRA) help treat APL (Acute Promyelocytic Leukemia)? |
|
Definition
| ATRA binds to PML-RARalpha so it can dissociate from transcription repressors and bind to RA-responsive genes. |
|
|
Term
| How does Vitamin A affect Measles? |
|
Definition
| Vitamin A deficiency makes measles more severe and increases fatality. |
|
|
Term
| How does vitamin A overdose affect pregnancies? |
|
Definition
| Over-regulation of RA-gene expression causes birth defects |
|
|
Term
| What are the forms of Vitamin E in the body? |
|
Definition
| 4 tocopherols and 4 tocotrienols |
|
|
Term
| What is the major vitamin E content of the diet? |
|
Definition
|
|
Term
| Why does Vitamin E have antioxidant properties? |
|
Definition
| It can donate its Hydrogen from the OH group of the chromanol ring. |
|
|
Term
| What is alpha-tocopherol transfer protein (alphaTTP)? |
|
Definition
| Critical regulator of Vitamin E by transporting hydrophobic vitamin E molecules to VLDL. |
|
|
Term
| What causes Ataxia with Vitamin E deficiency (AVED), and what characterizes it? |
|
Definition
Mutations in alphaTTP.
Low vitamin E levels with progressive neurodegeneration. |
|
|
Term
| Why does chronic vitamin E deficiency cause neurological degeneration? |
|
Definition
| There is an increase in oxidative stress that damages neurons in the brain. |
|
|
Term
| What can be used to treat the neurological symptoms associated with vitamin E deficiency? |
|
Definition
| alpha-tocopherol treatment |
|
|
Term
| What are the causes of Abetalupiproteinemia (ABL)? |
|
Definition
| Loss of function of MTP gene so beta-lipoproteins do not assemble. |
|
|
Term
| What are the main forms of Vitamin K in the body? |
|
Definition
K1: phylloquinone
K2: menaquinone |
|
|
Term
| What is vitamin K epoxide reductase (VKOR)? |
|
Definition
| It regenerates Vitamin K to its reduced form, KH2, from KO. |
|
|
Term
| Why is vitamin K an antidote to warfarin (a coumadin) overdose? |
|
Definition
| It acts as a competitive inhibitor to VKOR |
|
|
Term
| What will vitamin K in its fully reduced state act as a cofactor for? |
|
Definition
| The gamma-carboxylation of Glu into gamma-carboxyglutamic acid (Gla) |
|
|
Term
| Why does vitamin K deficiency cause impaired blood clotting? |
|
Definition
| Coagulation factors II, VII, IX, and X need to be gamma carboxylated by the vitamin K dependent g-carboxylase |
|
|
Term
| What will Vitamin K deficiency in newborns causes? |
|
Definition
| Vitamin K deficiency Bleeding (VKBD) |
|
|
Term
| What are the first signs of vitamin K deficiency? |
|
Definition
| Under-carboxylation of extrahepatic Gla proteins |
|
|
Term
| What is Matrix Gla Protein (MGP)? |
|
Definition
| It acts as a Ca2+ sponge to soak up Ca2+ and prevent crystallization in the tissues |
|
|
Term
| What will MGP deficiency cause? |
|
Definition
| Calcium crystallization that causes cell damage and death |
|
|
Term
| What is the cholesterol ratio? |
|
Definition
| Total cholesterol to HDL-cholesterol ratio |
|
|
Term
| What is the recommended normal cholesterol ratio? |
|
Definition
|
|
Term
| What causes abetalipoproteinemia? |
|
Definition
| Deficiencies in ApoB48 and ApoB100 causing low plasma chylomicron and VLDL levels. |
|
|
Term
| What is the first sign of the development of atherosclerosis? |
|
Definition
|
|
Term
| Why does LDL have atherogenic effects? |
|
Definition
| It gets easily trapped and oxidized inside the intima of the arteries, and it causes atherosclerotic plaques. |
|
|
Term
| What are the normal levels for HDL, LDL, Total Cholesterol, and Triglyceride? |
|
Definition
HDL: ≥ 60 mg/dL
LDL: < 100 mg/dL
Total: < 200 mg/dL
TG: <150 mg/dL |
|
|
Term
| What are the dietary essential fatty acids? |
|
Definition
| linolenic acid and linoleic acid |
|
|
Term
| How does Ezetimibe affect cholesterol levels? |
|
Definition
| It blocks the internalization of NPC1L1/cholesterol complex, thus reducing the small intestine ability to absorb dietary cholesterol |
|
|
Term
| What effect does colestipole and cholestyramine have on cholesterol levels? |
|
Definition
| It prevents the absorption of ASBT of bile salt in the ileum so the liver requires more cholesterol to synthesize bile salts, thus more LDLR are expressed and more LDL is taken from circulation. |
|
|
Term
| How do Statin drugs affect cholesterol levels? |
|
Definition
They have a structure moiety that resembles HMG-CoA, so they act as potent inhibitors of human HMG-CoA reductase.
De Novo cholesterol synthesis is inhibited. |
|
|
Term
| What are Fibrates and Glitazones? |
|
Definition
Activators of PPAR (peroxisome proliferation activation receptor), which act as ligand-dependent transcription factors to regulate gene expression.
Used as anti-hypertriglyceridemia drugs.
Mildly increase ApoA1 (HDL) synthesis |
|
|
Term
| What PPAR does Fibrate and Glitazone activate? |
|
Definition
Fibrate: PPARalpha
Glitazone: PPARgamma |
|
|
Term
| How does inhibition of PCSK9 affect plasma LDL levels? |
|
Definition
It increases the number of LDLR receptors to increase clearance rate from the plasma.
LDL plasma levels are lowered. |
|
|
Term
|
Definition
| An antibody to human PCSK9 |
|
|
Term
| How will CETP inhibitors affect cholesterol levels? |
|
Definition
| Marked increases in HDL levels and moderate decreases in LDL levels without toxicity. |
|
|
Term
| What is the role of CETP? |
|
Definition
| It transfers the CE generated by LCAT to VLDL and LDL |
|
|
Term
| Where does the brain derive most of its cholesterol? |
|
Definition
| De novo synthesis since the BBB prevents uptake of lipoproteins. |
|
|
Term
| What are the major cholesterol pools of the CNS? |
|
Definition
Myelin sheaths of oligodendroglia.
Plasma membranes of astrocytes and neurons. |
|
|
Term
| What are the major lipid constituents of myelin? |
|
Definition
| Cholesterol, phospholipids, and glycosphingolipids. |
|
|
Term
| When is the highest rate of cholesterol synthesis in humans? |
|
Definition
| The first postnatal weeks. |
|
|
Term
| When does the peak of the myelination process occur? |
|
Definition
| In correlation with the highest rate of cholesterol synthesis |
|
|
Term
| What happens of cholesterol biosynthesis is deficient during development? |
|
Definition
| The myelination process is delayed. |
|
|
Term
| What is the major source of apoE in the CNS? |
|
Definition
|
|
Term
| What roles does ABCA1 have with ApoE? |
|
Definition
| It loads lipids onto ApoE |
|
|
Term
| What is the major apolipoprotein in HDL in the CNS? |
|
Definition
|
|
Term
| What transports cholesterol synthesized by astrocytes in the CNS? |
|
Definition
| ApoE via endocytosis by LDLR family members |
|
|
Term
| What is the cholesterol from ApoE-containing lipoprotein particles used for? |
|
Definition
| Synaptogenesis and maintenance of synaptic connections |
|
|
Term
| What is Niemann-Pick Type C (NPC)? |
|
Definition
"Childhood Alzheimer's"
Neurogenerative disease that causes deterioration in memory and balance, lung and liver failure, delayed motor development, and seizures. |
|
|
Term
| What are the two mechanismsto take care of excess amounts of cholesterol inside neurons? |
|
Definition
1. ABCA1-dependent export.
2. ACAT-dependent conversion of cholesterol into CE and storage in lysosome-like storage organelles (LSO). |
|
|
Term
| How is cholesterol esters released from LSOs when needed? |
|
Definition
|
|
Term
| What deficiency causes NPC? |
|
Definition
|
|
