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Biochem Block 4

alcohol an organic molecule with one or more hydroxyl groups attached to carbon atoms
serine The amino acid _______is an alcohol (monohydric)
glycerol The amino acid _______is an alcohol (trihydric):
Entner-Douboroff pathway Pulque/mescal/tequila produced by bacterial fermentation (Zymomonas mobilis) using the _______-_________ pathway
3 – 4 g of ethanol Fermentation in the gut produces about____g of ______per day, most of which is absorbed
(9 – 15% by vol) Wines – fermented grape juice - alcohol content medium (__-__% by vol)
(25 – 50 % by vol) Spirits – made from fermenting almost anything and distilling – alcohol content high (__-__% by vol)
fractional percentage For medico-legal use, alcohol measurement of ______ _______ is used (e.g. 0.11%) (% by volume in blood)
.08% All 50 states have now set ____% blood alcohol concentration (BAC) as the legal limit for driving under the influence (DUI) or driving while impaired (DWI).
0.06–0.10% at what range of % blood alcohol concentration (BAC) does a person experience impairment of:Reasoning,Depth perception,Peripheral vision, Glare recovery and behavioral changes such as;Blunted feelings, Disinhibition, Extroversion
≥0.40% (about 75mM) at ~ what % blood alcohol concentration (BAC) does a person experience impairment of ;Breathing & Heart rate, General lack of behavior, Unconsciousness, Death
liver; 85-98 % of ethanol is metabolized in the ____ nearly every tissue has some alcohol dehydrogenase.
alcohol dehydrogenase (ADH) Major enzyme for alcohol metabolism is_________ , a cytosolic enzyme.
NADH, acetaldehyde, acetic acid. Major products of ethanol metabolism are_______, _______(toxic) and ________
acetic acid Acetaldehyde is oxidized to _______ in mitochondria.
acetyl CoA Acetic acid is activated to_______ in peripheral tissues especially skeletal muscle.
seven , chromosome 4 Humans have____#___ genes encoding for alcohol dehydrogenase on chromosome ___#___
zinc ion ADH peptides form primarily homo-dimers and contain a ____ ion as a prosthetic group.
ADH 3 (chi subunit) which alcohol dehydrogenase (ADH) is mainly in liver but does not oxidize ethanol, rather mainly long-chain alcohols.
ADH 2 (pi subunit) which alcohol dehydrogenase (ADH) is found mainly in liver but it has a high value of Km (30 mM
ADH 1 which alcohol dehydrogenase (ADH) is the most prevalent, found mainly in liver and adrenals and little to none in most other tissues. has Km = 0.05 to 4 mM for ethanol. account for the bulk of ethanol oxidation at lower concentrations of ethanol.
ADH 4 (sigma subunit) which alcohol dehydrogenase (ADH) is found mainly in upper GI tract and the mouth and esophagus down to the stomach. It has a high Km of 28 mM. It is very active toward retinol, forming retinal.
ADH 5 which alcohol dehydrogenase (ADH) is found mainly in fetal liver.
Microsomal Ethanol Oxidizing System, MEOS or CYP2E1 A higher proportion of ethanol is oxidized by__________ at higher concentrations of ethanol than by ADH1. It also has the highest activity toward ethanol.
Microsomal Ethanol Oxidizing System, MEOS or CYP2E1 __________oxidizes ethanol to acetaldehyde. Both NADPH and ethanol donate electrons to oxygen to form water. Is a cytochrome P450
Acetaldehyde _______ is formed at a faster rate with the Microsomal Ethanol Oxidizing System, MEOS or CYP2E1 , increasing the risk of hepatic injury and injury to the tissues as well.
reactive oxygen species[ROS] Increased CYP2E1 leads to increased production of____ .
inhibits The presence of ethanol _____ other CYP functions.
Phenobarbital (sleeping pills, treatment of epilepsy, etc.) people who take______drug induces its oxidative enzymes CYP2B1 and CYP2B2 50- to 100-fold.then combine ethanol consumption with _______[same drug] can develop toxic levels of _______[same drug] due to inhibition of CYP2B1 and CYP2B2 by ethanol.
cytosol acetaldehyde dehydrogenase (ALDH) ALDH1 is a minor form found in the _____.
the mitochondria acetaldehyde dehydrogenase (ALDH) ALDH2 is found in the ______ and is highly specific.
ALDH2*2 Individuals with one or two copies of_______have elevated concentrations of acetaldehyde (after ethanol consumption). No person homozygous for _______has ever been documented as an alcoholic.
Acetyl—CoA synthetase ACS1 orACS2. Acetate is readily converted to acetyl CoA by____ or_____
acetaldehyde dehydrogenase (ALDH) _________enzyme which catalyzse the conversion of acetaldehyde into acetic acid.
cholesterol and fatty acids. Acetyl—CoA synthetase [ACS1]is cytosolic and the acetyl CoA that is formed is then available for conversion to ______ and ______
carbon dioxide. Acetyl—CoA synthetase [ACS2] is mitochondrial and the acetyl CoA that is formed is readily oxidized to __________
NADH. Slow consumption of ethanol allows higher proportion to be oxidized by ADH but with less accumulation of ______
a net yield of 13 ATP per ethanol molecule. If ADH and ALDH are used for oxidation of ethanol. what is the net yield of___ ATP per ethanol molecule?
a net yield of 8 ATP per ethanol molecule. if MEOS[CYP2E1] is used, then what is the net yield of___ ATP per ethanol molecule? The NADH produced by the ADH reaction is offset by the NADPH used by the CYP2E1 reaction.
catalase The enzyme ______ is normally found in peroxisomes and can oxidize ethanol in the presence of H2O2,
Fatty acid Ethyl Ester synthase [FAEE synthase] Non-oxidative ethanol metabolism pathway uses what enzyme____? and can lead to persistant tissue damage or interference with PLD-mediated signalling.
Km 11 mM Microsomal Ethanol Oxidizing System, MEOS or CYP2E1 -The Km for ethanol is about ______
Km 0.05 to 4 mM ADH 1 has Km = ______to_____for ethanol.
Km (30 mM ADH 2 (pi subunit) has a Km of about______
alcohol Pregnancy + ______=the Leading cause of preventable birth defects/developmental disabilities in USA - also increased risk of miscarriage
Fetal alcohol syndrome Abnormal facial features - small eye openings - thin upper lip - no philtrum, Seizures - poor balance and co-ordination, Birth defects affecting heart, bone and kidney - also poor vision and lack of hearing
Alcohol-induced hepatitis & Cirrhosis ______ and _____ are caused by damage from free radicals generated by ethanol metabolism in the liver and possibly also by acetaldehyde adduct formation.
Hepatitis _______is inflammation of the liver that can lead to cell death.
Cirrhosis ________is the damage to the liver that is characterized by end-stage progression of fibrosis (scarring), disturbance of the normal architecture of the liver, associated with disturbance of blood flow, loss of function and ultimately hepatic failure.
Alcohol-induced cirrhosis ________ is found in about 9 % of all autopsies in the USA
B vitamins Uptake of all _______is inhibited by ethanol
cofactors Liver activation of vitamins to _______ is inhibited by ethanol
cancer Chronic long-term use of ethanol increases incidence of ______
fatty acid beta oxidation High [NADH]/[NAD] inhibits this metabolic pathway______.Fatty acids accumulate in the liver.
[NADH]/[NAD] Ethanol metabolism increases the [___]/[____] ratio mainly via ADH and ALDH reactions.
triacylglycerols High [NADH]/[NAD] stimulates formation of ________
DHAP High [NADH]/[NAD] stimulates the reduction of ________
acetyl CoA High [NADH]/[NAD] also inhibits the TCA cycle causing________ to accumulate.
Ethanol-Induced ketoacidosis High [NADH]/[NAD+] ratio depletes OAA blocking the conversion of acetyl CoA to citrate (i.e., TCA cycle) leading to the accumulation of acetyl CoA and causes_________
pyruvate, DHAP Gluconeogenesis, is inhibited by the depletion of______ , OAA and______
10:1 The ratio of NADPH:NADP+ is about _____ in cells at rest
1:100 to 1:1000. the ratio of NADH:NAD+ is ______to______ in cells at rest
ADH and ALDH ______and _____are not inhibited by high NADH levels. There are no other regulators of ____ or _____activity. The consequence is the accumulation of NADH driven by substrate availability.
glycerol 3-phosphate High [NADH]/[NAD+] causes ________ from DHAP to accumulate providing substrate for the re-esterification of the fatty acids.
ethanol-induced hyperlipemia. High [NADH]/[NAD+] causes glycerol 3-phosphate from DHAP to accumulate providing substrate for the re-esterification of the fatty acids.Triacylglycerol are loaded onto VLDL causing ________
hydroxybutyrate . Excess acetyl CoA leads to excessive ketone body formation, mainly __________
lactate dehydrogenase High [NADH]/[NAD+] ratio shifts the equilibrium of the_________ reaction towards lactate.
hyperuricemia and exacerbation of gout. Elevations in lactate may inhibit uric acid excretion by the kidney leading to ______and exacerbation of _______.
hypoglycemia High [NADH]/[NAD+] ratio shifts other gluconeogenic precursors (pyruvate, dihydroxyacetone phosphate and oxaloacetate) away from gluconeogenesis, leading to________ in fasted individuals.
hyperglycemia a rapid rise in [NADH]/[NAD+] levels can cause a transient ________by inhibiting glycolysis at the glyceraldehyde 3-phosphate dehydrogenase step.
adducts toxicity of ethanol is via acetaldehyde, which forms ______ with amino and sulfhydryl groups (-SH) of proteins and with nucleotides and phospholipids.
Adduct _______formation by acetaldehyde blocks protein and VLDL secretion leading to protein and lipid accumulation in the liver.
sulfhydryl Adduct formation with the ________ group of glutathione impairs cells ability to protect against lipid peroxidation damage
hydroxyethyl radical (CH3C.HOH) FAD and FMN and the heme in CYP2E1 lead to the abstraction of single electrons from ethanol generating the_________radical that can be released from the P450.
Polyunsaturated phospholipid fatty _____________acyl groups are major targets of peroxidation by free radicals.
omega-3 fatty acids Other oxygenated α,β-unsaturated aldehydes (OαβUAs) are generated also, which can also come from _________
7 kcal/g Alcohol is a food. Caloric value is about ______ kcal/g
Disulfiram _____irreversibly binds Acetaldehyde dehydrogenase (ALDH) causing accumulation of acetaldehyde in the body resulting in a sick feeling. People taking __________, therefore, learn to avoid alcohol.
formaldehyde Methanol when consumed gets converted by Alcohol dehydrogenase (ADH) to________-a toxic product
formic acid formaldehyde-a toxic product, responsible for visual disturbance & metabolic acidosis of methanol poisoning. then forms________catalyzed by acetaldehyde dehydrogenase which is toxic as well.
methanol Ethanol when used in treatment of _________ poisoning, competes with ________ for ADH thus preventing accumulation of formaldehyde and thereby its toxic effects.
Ferrooxidase Fe2+ oxidized to Fe3+ by ________
Transferrin Fe3+ *moved by ______
Ferritin Fe3+ *stored in_______ . Blood ________ levels indicate iron storage in body (50-170 ug/dL = normal)
Wilson's disease a deficiency of Ceruloplasmin (a ferrooxidase) associated with ______disease
‘pyrrole’ rings Four smaller________ join up to make one larger porphyrin ring
protoporphyrin Heme molecule molecule, without the Fe, is a _______
glycine & succinyl CoA Synthesis of heme in cytoplasm and mitochondria from ______ & _________.
iron Four pyrrole rings of Porphobilinogen + _______ = heme
Amino-Levulinic-Acid (ALA) synthase _________ enzyme is feedback inhibited by end product heme.
inhibited by lead Amino-Levulinic-Acid (ALA) dehydratase inhibited by _____
Acute Intermittent Porphyria Porphobilinogen deaminase is defective, Build up of porphobilinogen & ALA, both excreted in urine, oxidizes to, port wine’ color, anxiety,confusion, paranoia, no photosensitivity
Vitamin B6 (PLP) Amino-Levulinic-Acid (ALA)synthase Needs ______ to carry the amine group from glycine to make ALA.
porphyrias Failure of heme synthesis pathway causes these type of disorders_________
Barbiturates drugs such as ________ increase p450 which increases heme use. = Decreases heme in body. Get no inhibition of ALA synthase Build up of porphobilinoge. Makes it worse
Porphyria Cutanea Tarda. Most common porphyria, Autosomal dominant,uroporphrynigen decarboxylase deficiency, Photosensitivity., Blistering, Increased hair growth[Hypertrichosis],Build up of ALA excreted in urine Oxidizes to red/brown to deep red, Sideroblasts
Sideroblasts Abnormal RBCs with perinuclear (between the two nuclear membranes) mitochondria. Iron accumulates in mitochondria forming a ring visible with staining
Ferrochetalase ________adds Fe2+ to protoporphyrin. Is inhibited by lead
inhibited by lead Ferrochetalase Is inhibited by_______= ‘Plumbism’
Erythropoietic porphyria Ferrochetalase deficiency causes a Buildup of Fe2+ in mito, Cause sideroblasts, Zn2+ binds instead & causes microcytic fluorescent RBCs, Photosensitivity, malformed teeth in this disease.
Amino-Levulinic-Acid (ALA) if you have a deficiency in Vitamin B6 (PLP) you will have decreased production of ________ an intermediate in the heme synthesis pathway.
Ferritin, protoporphyrin if you have iron deficiency you will have decreased levels of ________due to less iron being stored and increased levels of ________ due to iron not being inserted to make Heme.
Amino-Levulinic-Acid (ALA) , & protoporphyrin __________ and _________ accumulate in the urine in lead poisoning
bilirubin Heme ring degraded, cleaved & opened, becomes _______
Bilirubin _______added to bile & excreted. Makes poop brown & pee yellow
UDP Glucuronyl Transferase This enzyme is induced at birth. If slow to express get jaundiced infant. If deficient there is a build up of bilirubin. Treat with blue light phototherapy as bilirubin absorbs light & breaks into small water soluble fragments.
jaundice. Failure to excrete bilirubin =__________. Build up of bilirubin in body gives yellow tinge to skin & sclera & mucous membranes.
gallstones Acute jaundice, episodic, radiating pain in abdomen suggests ______ blocking bilirubin excretion
tyrosine Catecholamines (such as* dopamine, norepinephrine, & epinephrine) are derived from_______ and made by nerve tissues and adrenal glands.
Catecholamines __________(such as* dopamine, norepinephrine, & epinephrine) are derived from tyrosine and made by nerve tissues and adrenal glands.
monoamine oxidases. catecholamines are broken down by__________
phenylalanine _______ amino acid is a precursor to tyrosine.
histidine. Synthesis of histamine. By decarboxylation of ______ Stored in mast cells. Released in case of allergies, chemical stress.
serotonin. Synthesis of _________ By oxidation & decarboxylation of tryptophan. Multiple effects of deficiency, including depression
creatinine. Combine Glycine with part of Arginine R chain to make_______
Glycine, Arginine Combine ______ with part of _______R chain to make creatinine.
tyrosine Synthesis of melanin From _________
Porphyria Cutanea Tarda. uroporphrynigen decarboxylase deficiency causes this _______
hepatitis fast onset of jaundice, dull pain, fever = ______
sub-acute / liver obstruction slow onset of jaundice (weeks) = __________
Paracrine secreted into interstitial space (small spaces between tissues/organs) Short half life. Eg: neurotransmitters & prostoglandins.
Autocrine type of secretion where hormone binds cell that produced it (autoregulation) An example of an _____agent is the cytokine interleukin-1 in monocytes
Telecrine [endocrine] secreted into blood. Long half life. Include hormones secreted by hypothalamus, pineal gland, pituitary gland, thyroid, thymus, adrenal, pancreas etc. [insulin/glucagon]
Water soluble hormone __________hormones bind to receptor on cell surface, [can't freely enter the cell] ,Utilize second messengers & protein phosphorylation to cause enzyme activation or gene activation
protein kinases Water soluble hormones. Use of _______ to alter target enzyme activity.
cAMP pathway glucagon and epinephrin use the _______pathway
G protein cAMP pathway uses a _____protein
Adenylate Cyclase cAMP pathway uses the enzyme__________
cAMP cAMP pathway uses the second messenger ______
G protein PIP2 pathway uses a _____protein
Phospholipace C PIP2 pathway uses the enzyme__________
DAG, IP3, Ca2+ PIP2 pathway uses the second messengers ______
protein kinase A cAMP pathway uses the protein kinase____
protein kinase C PIP2 pathway uses the protein kinase____
cGMP pathway _______ pathway does not use a G protein [NOT a G protein So no 7-helix domain]
Guanyl Cyclase cGMP pathway uses the enzyme__________
cGMP cGMP pathway uses the second messenger ______
protein kinase G cGMP pathway uses the protein kinase____
cGMP Atrial Natriuretic Factor (ANF)and Nitric Oxide[NO] use the _______pathway causing Vasodilation
Atrial Natriuretic Factor (ANF) Hormone (peptide)________Controls body fluid volume Released by heart muscles in response to high blood volume. Causes sodium loss.
Insulin receptor. ________Receptor is a Tyrosine Kinase (not a 7-helix transmembrane protein)Tyrosine kinase enzyme adds phosphates to its own tyrosines
α-GTP _______ moves to & activates/inhibits adenylate cyclase or phospholipase
IRS-1 Insulin receptor, Once phosphorylated, tyrosine kinase binds substrate ________
SH2 Other proteins with ____ domains can then bind IRS-1
SH2 ______domains allow binding to phosphorylated tyrosines
p21-ras Protein phosphatases are Activators of________ (a GTPase)
Phospha-tidyl-inositol-3 kinase (PI-3 kinase) a kinase which increases GLUT 4 in membrane
dephosphorylate Insulin activates protein phosphatases to_________ enzymes, Less glycogen breakdown
phosphorylate Glucagon activates protein kinase A to ________ enzymes Increased glycogen breakdown
ADP-ribose Some bacterial exotoxins add _______ to the G protein α subunit. This inactivates the G protein
Lipid soluble hormones _________ hormones such as: Estrogen, testosterone, progesterone, cortisol. Do not need membrane receptor as can diffuse into cell. Bind receptors inside cell.
cortisol Example of lipid hormone is the activation of PEPCK gene by _____
zinc-finger Receptors for lipid soluble hormones bind DNA using __________protein domains, acting as transcription factors to regulate gene expression
gluconeogensis High stress-->Cortisol-->increases this metabolic pathway?_________
isosorbide dinitrate this drug activates guanyl cyclase
sildenafil this drug inhibits cGMP phosphodiesterase in vascular smooth muscle
ATP _______ generated by oxidation of glucose, fatty acids, and amino acids
G6P, Pyruvate & Acetyl CoA ______, _________ & ______ are Junction Points of Pathways
lipids lymphatic system carries _______ from intestines to liver.
adipose tissue _________ synthesizes , stores, and mobilizes triacylglycerols
liver this organ processes fats, carbohydrates, proteins from diet; synthesizes and distributes lipids, ketone bodies and glucose for other tissues; converts excess nitrogen to urea.
120g Brain consumes_______ glucose / day
glycogen Muscles use glucose, fatty acids, and ketone bodies. Has large storage of______ (about ¾ of all _______ in body.)
Fatty acids _______are preferred in resting muscles and cardiac muscle (aerobic conditions).
Glucose ________ is preferred fuel for rapid bursts of activity -> produces lactate (anaerobic). (Has Glut4)
Kidney this organ uses glucose in well fed states & ketone bodies under starvation condition. Important site of gluconeogenesis under starvation conditions (1/2 of blood glucose).
Liver & Brain. Insulin has no direct effect on glucose uptake in_____ & _____. (Uses GLUT2 & 7, not GLUT 4 glucose transporter. ) (still insulin sensitive, but higher Km)
Insulin in the presence of_______ , Glut4 vesicles fuse with the plasma membrane, Glut4 allows glucose to enter the cell.
glycogenesis & lipogenesis Insulin plays role in these 2 metabolic pathways_______&________ in the liver.
alanine Degradation of proteins in muscle or transamination of pyruvate in muscle produces________
Acetyl CoA Breakdown of fatty acids produces_______ . Used for energy, sterol synthesis or ketone bodies
gluconeogenesis insulin suppresses ______ by the liver
glycolysis insulin -> accelerates_______ in liver -> increases synthesis of fatty acids
K+ , Ca2+ Increased blood sugar enter pancreas B cell via GLUT 2. Glycolysis & ATP production causes depolarization of membrane by ____channel. _____ ions enter & cause release of insulin by exocytosis
Glucokinase enzyme________ (liver & pancreas) activity increases with glucose. Not inhibited by increased G6P.
Hexokinase enzyme________ (muscle & other tissues) activity increases with glucose but inhibited by G6P. Much higher affinity but lower Vmax.
Glucagon stimulates gluconeogenesis in liver, and inhibits glycogen & fatty acid synthesis
synthesizes Re-fed state (just eaten, but still low blood sugar) Liver still ________glucose to refill liver’s glycogen stores (from lactate, glycerol, and carbon skeletons of amino acids
40- 60mg/100 ml Blood-glucose level must be above ____-____mg/____ ml for survival
~1-2days glucose/glycogen reserves are exhausted in~____#days
ketone bodies After 3 days of starvation (no glycogen) ______ from liver released into blood. Brain and heart use______ as fuel
proteins After depletion of TAG stores -> ________degradation accelerates -> death due to loss of heart, liver, and kidney function.
ketoacidosis High levels of ketone bodies cause_______ in blood and dehydration = coma
Diabetes mellitus _________– Insulin insufficiency, High blood-glucose level but starvation-like state at cell level
Type I diabetes: insulin-dependent (no insulin made.caused by autoimmune destruction of pancreatic β-cells .before age 20. Starvation mode + high blood-glucose level. Glucose entry into cells is blocked. Glucose/H2O excreted into urine -> feel hungry & thirsty.
Type II diabetes: insulin-independent (insulin made, but cells not responding) Normal / high level of insulin in blood . Develops in middle-aged, obese people.
insulin & leptin Two important molecules for caloric homeostasis and appetite control are _____ & ______.
leptin High ______ = metabolize more and eat less
less, more Low leptin = metabolize ____ and eat _____
leptin, heat High fat = high ______= high metabolism = increased_____ generation
lactate Sprinting = anaerobic, makes ______
CO2 Distance running = aerobic, makes _____
myosin ATP directly powers _______ = responsible for muscle contraction
creatine phosphate _________ can generate ATP under intense muscle contractions for 5-6 seconds
blood glucose, fatty acids, and ketone bodies when Dr. Young is watching Netflix[light activity or rest] which 3 fuel sources is his body using?____,______, and _____
hypermetabolic Metabolism post-injury:Body core temperature decreases proportional to severity of injury.Oxygen consumption increases to generate heat. Results in ______ state
hypermetabolic state Increased HR, BP, body temp, protein & lipid catabolism
Insulin [Hormone] Facilitates the transport of glucose into muscle and adipose cells. Facilitates the conversion of glucose to glycogen for storage in the liver and muscle. Decreases the breakdown and release of glucose from glycogen by the liver
Insulin [hormone] Stimulates lipogenesis- the transport of triglycerides to adipose tissue
Insulin [hormone] Inhibits lipolysis – prevents excessive production of ketones or ketoacidosis
disulfide A larger precursor preproinsulin .Remove a 23 aa signal sequence and form three ______ bonds you get Proinsulin.
C peptide if you take Proinsulin and Remove the _______ you get Mature insulin which has A and B chains.
Type 1 Diabetes Mellitus body’s immune system destroys pancreatic beta cells, Low or absent endogenous insulin, Dependent on exogenous insulin for life,Onset generally < 30 years, 5-10% of cases of diabetes,Onset sudden, 3 P’s: polyuria, polydipsia, polyphagia
Type 2 Diabetes Mellitus Insulin levels may be normal, elevated or depressed (Depending on year since onset)Characterized by insulin resistance, Diminished tissue sensitivity to insulin. Multifactorial etiology Often occurs >40 years
Gestational Diabetes A form of glucose intolerance that is diagnosed in some women during pregnancy. occurs more frequently among African Americans, Hispanic/Latino Americans, and American Indians. more common among obese women and women with a family history of diabetes.
Latent Autoimmune Diabetes in Adults (LADA) a form of autoimmune (type 1 diabetes) which is diagnosed in individuals who are older than the usual age of onset of type 1 diabetes. Often, patients are mistakenly thought to have type 2 diabetes, based on their age at the time of diagnosis.
MODY (maturity-onset diabetes of youth) a monogenic form of diabetes, autosomal dominant. Mutations of any several transcription factors or in the enzyme glucokinase lead to insufficient insulin release from pancreatic ß-cells, Different subtypes are identified based on the mutated gene.
Secondary Diabetes Mellitus diabetes caused indirectly via;Acromegaly, Cushing syndrome, Thyrotoxicosis, Pheochromocytoma,Chronic pancreatitis, Abdominal trauma, Cancer,Drug induced hyperglycemia:
polydipsia abnormally great thirst as a symptom of disease (such as diabetes) or psychological disturbance.
polyuria production of abnormally large volumes of dilute urine.
polyphagia is a medical sign meaning excessive hunger and abnormally large intake of solids by mouth.
anti GAD (Glutamic acid decarboxylase)-antibodies Patients with Latent Autoimmune Diabetes in Adults (LADA) will have presence of these anti-_______ antibodies and will progress to insulin requirement within 6 years.
metformin The potential value of identifying patients with LADA, which are at high risk of progression to insulin dependence includes: the avoidance of using __________ treatment the early introduction of insulin therapy
glucokinase, transcription factor Within MODY, the different subtypes can essentially be divided into 2 distinct groups:___________ MODY and __________ MODY, distinguished by characteristic phenotypic features and pattern on oral glucose tolerance testing.
low-dose sulfonylurea Glucokinase MODY requires no treatment, while transcription factor MODY (i.e. Hepatocyte nuclear factor-1 alpha) requires _______________therapy.
PNDM (permanent neonatal diabetes mellitus: this diabetes caused by KCNJ11, ABCC8 and /or Kir6.2 mutation) requires high-dose sulfonylurea therapy.
Beta-blockers Atypical Antipsychotics :_____________ - Inhibit insulin secretion
Diabetes Cardiovascular- Atherosclerosis, MI ,Retinopathy-Neovascularisation Pathology, Nephropathy-Urine shows Microalbuminuria, Neuropathy- Peripheral tingling and numbness,Microvascular disease, AGEs (advanced glycation end-products) are complications of?
Neuropathy Peripheral tingling and numbness
Nephropathy Urine shows Microalbuminuria.
prediabetes is a term used to distinguish people who are at increased risk of developing diabetes. People with _________have impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Some people may have both IFG and IGT.
impaired fasting glucose (IFG) is a condition in which the fasting blood sugar level is elevated (110 to 125 milligrams per decilitre or mg/dL) after an overnight fast but is not high enough to be classified as diabetes.
impaired glucose tolerance (IGT) is a condition in which the blood sugar level is elevated (140 to 199 mg/dL after a 2-hour oral glucose tolerance test), but is not high enough to be classified as diabetes.
[1] dieat and exercise [2] oral hypoglycemic therapy [3] insulin therapy The major components of the treatment of diabetes are:
sulfonylureas: Glipizide[Glucotrol] drug therapy that stimulates insulin release from the pancreas
Biguanides: Metformin[Glucophage] drug therapy that increases glucose uptake by muscle; and decreases glucose production by liver
Diabetic Ketoacidosis (DKA) Absolute (or near-absolute) insulin deficiency, resulting in Severe hyperglycemia, Ketone body production, Systemic acidosis,Develops over hours to 1-2 days, Most common in type 1 diabetes, but increasingly seen in type 2 diabetes
Hyperglycemic Hyperosmolar State (HHS) Severe relative insulin deficiency, Profound hyperglycemia and hyperosmolality (from urinary free water losses) No ketone production or acidosis, Develops over days to weeks. Typically type 2 or unrecognized diabetes,Higher mortality rate
Hyperglycemic Hyperosmolar State (HHS) commonly with renal failure,Insufficient insulin-> hyperglycemia but sufficient insulin for suppression of lipolysis and ketogenesis. Absence of significant acidosis. Often identifiable precipitating event (infection, MI)
Plasma glucose >600 mg/dL Hyperglycemic Hyperosmolar State (HHS) plasma glucose levels are _______mg/dL
Plasma glucose >250 mg/dL Diabetic Ketoacidosis (DKA) plasma glucose levels are _______mg/dL.
<12 mEq/L The normal anion gap is _________
anion gap In ketoacidosis, the _________above 12 mEq/L is composed of _______ derived from keto-acids.
Hyperchloremic Metabolic Acidosis (Non-anion Gap) is common during recovery from DKA due to, Fluid replacement with saline (NaCl), Renal loss of HCO3
B-hydroxybutyric acid (B-OH B) In DKA, the dominant ketoacid is ________, especially in cases of poor tissue perfusion/lactic acidosis.
acetoacetic acid (AcAc) During recovery from DKA, the balance shifts to _________acid (AcAc)
acetone, acetoacetate (AcAc) Unless B-hydroxybutyrate (B-OH B) is specifically ordered, the ketone bodies are estimated by the nitroprusside reaction in the lab, which measures only _________and ________
nitroprusside reaction ketone bodies are estimated by the _________reaction in the lab,
anion gap The best biochemical indicator of resolution of keto-acid excess is simply the_______
Diabetic Ketoacidosis (DKA) Kussmaul respirations,Fruity breath, Relative hypothermia Tachycardia, Supine hypotension, orthostatic drop of blood pressure are signs of _________
Formula for Estimating Serum Osmolality 2 x [Na+ mEq/L] + [glucose mg/dL] / 18 + [BUN mg/dL] / 2.8 is the formula for estimating what?
Cerebral edema ______ is a swelling in the brain caused by the presence of excessive fluid. it is a dreaded complication of DKA or its management in childhood. Mortality may be 24%, with significant morbidity among survivors
Potassium ________ is dominantly intracellular. Urinary losses occur during evolution of DKA (due to glycosuria). Total body _______ stores are greatly reduced in any patient with DKA. _______ moves from inside the cell to the extracellular space (plasma)
hypokalemia Life-threatening _________ can develop during insulin treatment
Weight (kg)/Height (m2 what is the formula for calculating Body Mass Index (BMI) ?
intra-abdominal In both men and women, excess _________ adipose tissue correlates strongly with cardiovascular disease, dyslipidemia, hypertension, stroke and type 2 diabetes.
iliac crest, lower rib. Body Fat Distribution-Waist Circumference Measured at the mid-point between the _______ and the______.
> 40 inches for men , > 35 inches for women Upper body obesity defined as a waist circumference: >______ inches for men > ______ inches for women
α-MSH (melanocortin) Anorexigenic neurosecretory cells ->_____ =eat less, burn fuel
NPY Orexigenic neurosecretory - cells to release _____= eat more
Ghrelin _______is a Peptide hormone from stomach. Appetite stimulant between meals. Injection of ______ causes intense hunger
PI-3K One possible explanation for the observed interaction between leptin and insulin is that Both phosphorylate insulin receptor substrate-2 (IRS-2)--> ______= an inhibition of food intake.
Orlistat (Xenical) _____is a drug therapy for obesity. Activity occurs in the stomach and small intestine. Inhibits gastric and pancreatic lipases. 30% of ingested fat is unabsorbed and excreted.
Sibutramine (Meridia) _____is a drug therapy for obesity. It is a Serotonin and norepinephrine re-uptake inhibitor SNRI). Drug reduces body weight by: Decreasing food intake in rats, Stimulates thermogenesis in rats
Metabolic Syndrome 3/5 =______ 1. Abdominal obesity: waist circumference > 102 cm in men and > 88cm in women; 2. Hypertriglyceridemia: > or = to 150mg/dl 3. Low HDL: <40 mg/dl in men, <50 in women 4. High BP: > or = 130/85 mm Hg 5. High FBS: > or = 110 mg/dl
Adiponectin hormone protective in the vasculature, inhibits foam cell formation & vascular remodelling, stops atherosclerotic plaque. improves insulin sensitivity & opposes the development of hyperglycaemia, therefore anti-diabetic as well as anti-atherosclerotic.
IL-6 _____ is a systemic inflammatory hormone that exerts adverse, pro-atherogenic effects in the vasculature._____also exacerbates insulin resistance and is therefore both pro-atherogenic and pro-diabetic.
TNFα _____ is a paracrine regulator in adipocytes. _____induced reductions in insulin sensitivity in adipocytes are partly responsible for the increased free fatty acid production and hypertriglyceridaemia characteristic of abdominal obesity.
PAI-1(Plasminogen activator Inhibitor) Increased ________secretion by intra-abdominal adipocytes shifts the balance of fibrinolysis towards a procoagulant state, increasing the risk of a morbid thromboembolic event
Adipocytokines these signalling molecules ________ have been associated with obesity and type 2 diabetes.
Steatosis (fatty liver) __________ is an accumulation of fat in the liver
irreversible Effects of malnutrition at a critical period are __________?
endometrium During the first few days after implantation: the nutrition of the blastocyst arises directly from the interstitial fluid of the ____________and from the surrounding maternal tissue
water First 2 months : embryo consists almost entirely of _______
Human Placental Lactogen (HPL): __________blocks the peripheral uptake and utilization of glucose by maternal tissue while promoting the mobilization and utilization of free fatty acid
leptin Placenta may secrete ______ to regulate maternal blood Fatty acid concentration.
IgM increased amounts of_____are found only during fetal infection in utero.
facilitated diffusion lactate Transports across the placenta by ______ and Co-transport with an hydrogen ion
insulinase this enzyme destroys maternal insulin
Active transport Iron and trace elements use this type of transport
1000 mg it is recommended to supplement iron in pregnancy with total ________ mg throughout pregnancy
Intrauterine growth restriction (IUGR) refers to a condition in which an unborn baby is smaller than it should be because it is not growing at a normal rate inside the womb.
Barker or “Thrifty Phenotype” Hypothesis ____or_______hypothesis says that reduced fetal growth is strongly associated with a number of chronic conditions later in life. [ coronary heart disease, stroke, diabetes, and hypertension, metabolic syndrome]
neural tube deficits Overweight & Obese Mothers are twice as likely to have babies that are larger with _____ _____ ______ and have a greater risk of heart defects.
obesity, hypertension Underweight Mother High risk of having a low-birthweight baby which are 40 times more likely to die in first month. Risk for _____ & _________ later in life, and have a lower IQ, Short stature
Folate has a Role in cell reproduction. during pregnancy it should be Increased from 400-600 mcg/day. Prevents neural tube deficits
Vitamin B12 Needed to assist folate in manufacture of new cells. Found in animal products. Vegans need fortified foods or supplements
calcium Intestinal absorption of ______ doubles early in pregnancy Final weeks, more than 300 mg of _____ are transferred to fetus
Vitamin C _______rich foods enhance absorption of iron
zinc _____Needed for DNA, RNA & protein synthesis. Deficiency predicts low birthweight. Found in foods of high protein content Iron interferes with______ absorption
3 ½ pounds healthy pregnancy a Normal-weight woman is ~ _____ the first trimester and 1 pound/week thereafter with an overall range of 25- 35lb [ 11.5-16kg]
Pica, iron _____: Craving items such as laundry starch, clay, soil, or ice. Common among African American women. Often associated with _____deficiency
oral glucose tolerance test [OGTT] for pregnant women to diagnose gestational diabetes.
Preeclampsia a condition in pregnancy characterized by high blood pressure[hypertension], sometimes with fluid retention and proteinuria. May experience convulsions
Listeriosis this Foodborne illness_____Can cause miscarriage, stillbirth
330kcalories/day a new mother needs an extra_____kcalories/day to be able to breastfeed her child.
Colostrum this (premilk substance) offers Immunological protection Maternal immune factors,Enzymes that offer protection, passed to baby through breastmilk
breastmilk Alpha-lactalbumin is a specific protein found in ________
infant formula _______ has lower fat[49%], but has higher protein[9%] and carbohydrates [42%] than breastmilk. However,All _____need to be iron fortified and have risks of over-dilution & contamination
iron, vitamin C Cow’s milk Is a poor source of _____. Higher in calcium but lower in _______ .Higher protein can stress infant’s kidneys
canned vegetables, Honey for an infant avoid feeding _________because they are High in sodium. and ______ for Risk of botulism
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