Regulatory Enzymes You gotta know Flashcards
What activates pyruvate carboxylase?
Requires biotin and ATP Activated by acetyl CoA
What does pyruvate carboxylase do?
Pyruvate to oxaloacetate
What does PEP carboxykinase do?
Oxaloacetate to PEP requiring GTP
What does Fructose 1,6 bisphosphatase do?
Fructose 1,6 bisphosphate to fructose 6 phosphate
What activates fructose 1,6 bisphosphate?
Citrate
What deactivates fructose 1,6 bisphosphatase
AMP F2,6Bisphosphate
What is the action of glucose 6 phosphate
Glucose 6 phosphate to glucose
What is the finding of pyruvate dehydrogenase deficiency?
Neurologic defects Lactic acidosis Increased serum alanine
What is the treatment for pyruvate dehydrogenase deficiency?
Increased intake of ketogenic nutrients (high fat content or increased ketogenic amino acids lysine and leucine)
What activates pyruvate dehydrogenase complex?
NAD+ ADP Ca2+
What is the difference between hexokinase and glucokinase?
Hexokinase is found in most tissues except liver and pancreatic beta cells with a lower affinity and lower capacity Hexokinase is unaffected by insulin It is inhibited by glucose 6 phosphate
What is the activator of glycolysis?
AMP, F26BP
What is the inhibitor of glycolysis?
ATP, citrate
What is the activator of gluconeognesis?
Citrate
What is the inhibitor of gluconeogenesis?
AMP, fructose 2,6 bisphosphate
What is the activator of the TCA cycle?
ADP
What is the inhibitor of the TCA cycle?
ATP, NADH
What are the inhibitors of glycogenesis?
GLucose 6 phosphate, insulin, cortisol
What is the inhibitor of glycogenesis?
Epinephrine, glucagon
What is the activator of glycogenolysis?
Epinephrine, glucagon, AMP
What is the inhibitor of glycogenolysis?
Glucose6 phosphate, insulin, ATP
What are the activators and inhibtors of the HMP shunt?
Glucose 6 phosphate dehydrogenase NADP+ activates NADPH inhibits
What are the inhibitors of de novo purine synthesis?
AMP, IMP, GMP
What is the activator of the urea cycle?
N-acetylglutamate
What is the activators of fatty acid synthesis?
Insulin, citrate activate
What is the inhibitors of fatty acid synthesis?
Glucagon and palmitoyl-CoA
What is the inhibitor of fatty acid oxidation
Malonyl-CoA
What is the activator of cholesterol synthesis?
Insulin, thyroxine
What are the inhibitors of cholesterol synthesis?
Glucagon, cholesterol
What are the activators of de novo pyrimidine synthesis?
ATP, PRPP
What are the inhibitors of de novo pyrimidine synthesis?
UTP
What process is affected by a lack of vitamin C?
- Antioxidation 2. Decreased iron absorption 3. Hydroxylation of proline and lysine in collagen synthesis 4. Decreased dopamine beta hyroxylase activity
What diseases are inherited by trinucleotide repeat expansion?
Huntington (CAG) Myotonic dystrophy (CTG) Fragile X syndrome (CGG) Fredreich ataxia (GAA)
What are the X recessive disorders?
Oblivious Females Will Often Give Her Boys Her x-Linked Disorders Ornitine transcarbamylase deficiency Fabry disease Wiskott-Aldrich syndrome Ocular albinism G6PD deficiency Hunter syndrome Bruton agammaglobulinemia Hemophilia (A and B) Lesch-BNyhan syndrome Duchenne muscular dystrophy
What are the areas where type 1 collagen may be found?
Bone, skin, tendon dentin, fascia, cornea, late wound repair White stuff
What are the areas where type 2 ollagen may be found?
Cartilage, vitreous body, nucleus pulposus CarTWOlage
What area where type 3 collagen are found?
Reticulin - skin, blood vessels, uterus, fetal tissue, granulaiton tissue Defective in Ehlers, Danlos syndrome
What area is type 4 collagen found?
Basement membranes, basal lamina, lens
What is the defect if I cell disease?
defect in N-acetylglucosaminyl-1-phosphotransferase leading to a failure of the Golgi to phosphorylate mannose residues leading to proteins being secreted extracellualrly rather than being delivered to lysosomes
What is the manifestation of I cell disease?
Coarse facial features, clouded corneas, crestricted joint movement, and high plasma levels of lysosomal enzymes
alpha amantin does what?
inhibits RNA polymerase 2 which makes mRNA
What are the sizes of RNAs relative to each other?
rRNA is the most numerous mRNA is the most massive tRNA is the tiniest
What enzymes carry out base excision repair?
GEL PLease 1. Glycosylase removes altered bases and creats an AP site 2. One or more nucleotides are removed by AP-Endonuclease, which cleaves the 5’ end 3. Lyase cleaves the 3’ end 4. DNA Polymerase-beta fills the gap 5. Lyase seals it
What is the defect that occurs in adenosine deaminase deficiency?
ADA is required for degradation of adenosine and deoxyadenosine If this enzyme is deficient lymphocytes die from increased dATP
What are the symptoms of HGPRT deficiency (Lesch-Nyhan
Hyperuricemia Gout Pissed off Retardation dysTonia
What is the built up substance in lesch-Nyhan?
Decreased purine salvage leading to increased conversion of xanthine to uric acid, which causes hyperuricemia and subsequent issues
What is the structure of cilia?
9 doublet + 2 singlet arrangement of microtubules connected to a basal body consisting of 9 triplets
What is Menkes disease?
X-recessive connective tissue diesease caused by impaired copper absorption and transport due to Menkes protein defect. Leads to decreased activity of lysyl oxidase and brittle kinky hair, growth retardation and hypotonia
What is the order of intermediates in the porphyrin pathway?
Ala Placed in Urine Cup Produces Heme Aminolevulinic Acid Porphobilinogen Uroporphyrinogen Coproporphyrinogen Protoporphyrin Heme
What are the order of enzymes in the porphyrin pathway?
Some Doctors Prescribe Unlimited F(ph)enobarbitol S = Ala synthase D = Ala Dehydratase P = Porphobilinogen deaminase U = Uroporphyrinogen decarboxylase F = ferrocheletase
What is the order of porphyrin diseases?
SLAP Sideroblastic anemia Lead Poisoning Acute intermittent Porphyria Porphyria cutanea tarda
What occurs in antiphospholipid syndrome?
Anticardiolipin antibodies cause false positive RPR and lupus anticoagulant Can also cause prolonged PTT which is not corrected by the addition of normal platelet-free plasma
What are the symptoms of antiphospholipid syndrome?
Diagnose based on history of thrombosis, or spontaneous abortion Lupus anticoagulant, anticardiolipin, anti-b2 glycoprotein antibodies
What is the difference between boerhaave and mallory weiss?
Boerhaave syndrome - transmural distal esophageal rupture with pneumomediastinum due to violent retching
Mallory Weiss - Partial thickness mucosal lacerations at gastroesophageal junction due to severe vomiting. Presents with hematemesis and may be misdiagnosed as ruptured esophageal varices
What is trousseau syndrome?
Redness and tendernes on palpation of extremities
What is the mechanism of metoclopramide?
D2 receptor antagonist leading to increased resting tone, contractility, LES tone, motility
This promotes gastric emptying, but does not influence colon transport time
Used for diabetic and postsurgery gastroparesis, antiemetic, persistent GERD
What is the mechanism and use of aprepitant?
Mech: Substance P antagonist. Blocks NK1 receptors in the brain
Use: antiemetic for chemotherapy induced nausea and vomiting
What is power?
1-beta
beta = type II error
What is the function of the glossopharyngeal nerve?
- Taste and sensation from posterior 1/3 of tongue
- Salivation from parotid
- Carotid body and sinus monitoring
- Elevation of the pharynx and larynx via stylopharyngeus
What is the function of the facial nerve?
- Facial movement
- Taste in anterior 2/3 tongue
- Lacrimaiton and salivation (submandibular and sublingual glands)
- Eyelid closing (orbicularis oculi)
- Auditory volume modulation (stapedius)
What are the functions of the vagus nerve?
- Taste from supraglottic region
- Swallowing
- Soft palate elevation
- Midline uvula
- Talking
- Cough reflex
- Parasympathetic to thoracoabdominal viscera
- Monitoring of aortic arch chemo and baroreceptors
What are the functions of the trigeminal nerve?
- Mastication
- Facial sensation (opthalmic, maxillary, mandibular divisions)
- Somatosensation from anterior 2/3 of tongue
Monckeberg sclerosis
Medium sized artery calcification of internal elastic lamina and media of arteries leading to stiffening without obstruction
Pipestem appearance on x-ray and does not obstruct blood flow
Intima not involved
Brugada syndrome
Autosomal dominant disorder most common in asian males where an ECG pattern of pseudo=right bundle branch block and ST elevation in V1-V3
Increased risk of ventricular tachyarrhythmias and SCD
What are the results of a C3 deficiency?
Increases risk of severe pyogenic sinus and respiratory tract infections
Increased susceptibility to type III hypersensitivity reactions
What are the results of C5-C9 deficiencies?
Terminal complement deficiency increases susceptibility to recurrent Neisseria bacteremia
What is the consequence of C1 esterase inhibitor deficiency?
Causes hereditary angioedema due to unregulaed activation of Kallikrein leading to increases bradykinin
Decreased C4 levels
DONT USE ACE INHIBITORS
What are the consequences of CD55 deficiency?
DAF deficiency leading to complement mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria
What are the activators of each version of the complement pathway?
- Alternative - spontaneous and microbial surfaces
- Lectin - microbial surfaces
- Classic - antigen antibody complexes
What are the results of beta and glucagon receptor activation?
- cAMP formation
- PKA activation
- Glycogen phosphotrylase kinase activation
- Phosphorylation and activation of glycogen phosphorylase
What are the results of insulin receptor activation?
- Tyrosine kinase dimer receptor activation
- Glycogen synthase activation
- Glycogen formation
What are the main characteristics of kartagener syndrome?
Primary: Dynein arm defect leading to immotile cilia.
Resultant:
- Decreased male and female fertility tue to immotile sperm and decreased cilia action in the fallopian tube.
- Because of this decreased motility, ectopic pregnancy is frequent in females
- Mucociliary escalator affected leading to bronchiectasis and recurrent sinusitis
- Dextrocardia (reversal of internal organs)
What two elements are required to sinthesize niacin?
Typtophan
B2 and B6
What are the resultant features of hyperacute graft rejection?
Widespread thrombosis of graft vessels leading to ischemia and necrosis from pre existing antibodies to donor antigen
REQUIRES IMMEDIATE REMOVAL
What are the features of acute rejection?
CD8 mediated activity against donor MHCs
Vasculitis of graft vessels with interstitial lymphocytic infiltrate
What are the features of chronic rejection?
CD4+ cells respond to recipient APCs presenting donor peptides
Recipient T cells secrete cytokines leading to proliferation of vascular smooth muscle, parenchymal atrophy, interstitial fibrosis and arteriosclerosis
What are the features of chronic rejection in
Lungs
Heart
Kidney
Liver
Lung: Bronchiolitis
Heart: Accelerated atherosclerosis
Kidney: Chronic graft nephropathy
Liver: Vanishing bile duct syndrome
What are the features of graft versus host disease?
Maculopapular rash, jaundice, diarrhea, hepatosplenomegaly
Usually occurs in bonemarrow and liver transplants
Beneficial in bone marrow transplant for leukemia
What drugs elicit a sulfa drug reaction?
Scary Sulfa Pharm FACTS
Sulfonamide antiiotics
Sulfasalazine
Probenicid
Furosemide
Acetazolamide
Celecoxib
Thiazides
sulfonylureas
Where does the PDA arise? What does it supply?
Right coronary artery
Supplies: AV node, posterior 1/3 of interventricular septum, posterior 2/3 of walls of ventricles, posteromedial papillary muscle
What is supplied by the left anterior descending artery?
Anterior 2/3 of interventricular septum, anterolateral pappilary muscle, and anterior surface of left ventricle
Salivary gland tumors can effect what nerve?
Facial nerve
What inhibits the rate limiting step of ALA synthase?
Glucose, heme
What are some of the resultant effects of osteopetrosis?
Bone fractures
Thrombocytopenia, anemia, leukopenia with extramedullary hematopoiesis due to bony replacement of the marrow
Vision impairment from impingement of cranial nerves
Hydrocephalus from narrowing of foramen magnum
RTA from lack of carbonic anhydrase leading to decreased reabsorption of HCO3- leading to metabolic acidosis
What is the major difference with how Lambert Eaton and Myasthenia gravis appears?
Muscle weakness worsens with use in myasathenia gravis as opposed to Lambert eaton which gets better with use. Lambert eaton doesnt affect the face either
What are the main effects of cortisol?
A BIG FIB
- Appetitie
- Blood pressure increase (alpha1 arteriole upregulation)
- Insulin resistance
- Gluconeogenesis, lipolysis, and proteolysis
- Fibroblast activity decreased
- Inflammatory and immune response decrease
- Bone formation decrease
What are the reasons for parathyroid disease for decreased Calcium despite increased PTH
vitamin D deficiency
Decreased calcium intake
Chronic renal failure
What are the reasons for decreased PTH and calcium
Surgical resection of parathyroid
Autoimmune destruction of parathyroid
What is the reason for increased PTH and Ca2+?
hyperplasia of parathyroid
Adenoma of parathyroid
Carcinoma
What is the reason for decreased PTH but high levels of calcium?
Excess Ca2+ intake
Cancer
Increased vitamin D
Whta are the three destinies for CO2 as it enters the plasma?
- Combines with CO2 to create H+ and HCO3- which diffuses out of the cell in exchange for Cl-
- Addition to Hb to form HbCO2
- Stays dissolved in the serum
What are the characteristics of strep bovis?
Gram + cocci, colonizes the gut
Can cause bacteremia and subacute endocarditis and is associated with colon cancer
(Bovis in the blood gives you Cancer in the Colon)
What is scabies?
Sarcoptes scabei infection of the skin leading to pruritus and serpinginous burrows (lines) in the webspace of the hands and feet. Common in children and crowded populations
Common causes of osteomyelitis in patients who are sexualy active
Neisseria gonorrhoeae (rare)
Septic arthritis more common
Common causes of osteomyelitis in patients who have sickle cell disease
Salmonella and Staph Aureus
Common causes of osteomyelitis in patients who have had joint replacement
S aureus and staph epidermidis
Common causes of osteomyelitis in patients who have vertebral involvement
S aureus and mycobacterium tuberculosis (Pott)
Common causes of osteomyelitis in patients who have had a cat bite
Pasteurella mutocida
Common causes of osteomyelitis in patients who have been abusing IV drugs
Pseudomonas, candida, S aureus
Microscopic appearance of acute inflammation
- Neutrophil, eosinophil, antibody, mast cell, basophil mediated
- Rapid onset and short duration
- Can completely risolve, form abscess, or progress to chronic inflammation
Microscopic appearance of chronic inflammation
Mononuclear cells and fibroblases
Persistent destruction and repair. Associated with blood vessel proliferation, fibrosis. Granuloma: Nodular collections of epithelioid macrophages and giant cells. Outcomes include scarring, amyloidosis, and neoplastic transformation
Difference between primary and secondary amyloidosis?
AL: deposition of proteins from Ig Light chains. Can occur as a plasma cell disorder or associated with myeloma. Often affects multiple organ systems including renal, cardiac, hematologic, GI, and neurologic
AA: chronic inflammatory conditions such as rheumatoid arthritis, IBD, spondyloarthropathy, familial Mediterranean fever, protracted infection. Fibrils composed of serum Amyloid A. OFten multisystem
What is P-glycoprotien?
Also known as multidrug resistance protein 1 (MDR1)
Classically seen in adrenocortical carcinoma but also expressed by other cancer cells
Function: Pump out toxins, including chemotherapeutic agents
Z values for 95 and 99 percent confidence interval
95 = 1.96
99 = 2.58
