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136 Cards in this Set
- Front
- Back
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Total energy expenditure is how many calories per kg/day?
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25-35
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Which amino acids can enter the metabolic pathways at pyruvate?
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ala, cys, gly, ser, thr
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Which amino acids can enter the metabolic pathways at alpha-ketoglutarate?
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pro, his, arg
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Which amino acid can enter the metabolic pathways at acetyl-coA?
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Ile
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What are the first two reactions in gluconeogenesis?
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pyruvate -> OAA -> PEP
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Why can glycogen be broken down to glucose quickly?
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it has branch points
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What is the purpose of the pentose shunt?
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make ribose sugars (purine/pyrimidine) and NADPH (for fatty acid synthesis)
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Insulin/glucagon is in general likely to cause phosphorylation/dephosphorylation?
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insulin = dephosphorylation, glucagon = phosphorylation
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What is the insulin responsive glucose transporter and where is it located?
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GLUT4 in skeletal and adipose tissue
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What is the glucose transporter in liver and pancreas beta cells?
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GLUT2
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What is the first thing that glucose is converted to after it enters the cells and what enzyme catalyzes this reaction?
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glucose-6-phosphate
hexokinase in skeletal muscle, glucokinase in liver and beta cell |
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At fasting blood glucose (5mmol/L), what are the rates of hexokinase and glucokinase?
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Hexokinase is at vmax, glucokinase is lower than km
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Is vmax higher for glucokinase or hexokinase?
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glucokinase
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Where does glucose primarily go to immediately after a meal?
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liver
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What are the three regulated steps of glycolysis?
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Glucose -> G6P
F6P -> F1,6P PEP -> pyruvate |
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Which enzyme catalyzes F6P -> F1,6P?
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phosphofructokinase 1
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What inhibits the action of PFK1?
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ATP and citrate
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What promotes the action of PFK1?
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F2,6P via F6P catalyzed by PFK2; PFK2 activated by insulin (dephos)
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Which enzyme catalyzes PEP -> pyruvate?
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pyruvate kinase
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What inhibits pyruvate kinase and how?
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glucagon, phosphorylation
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Which enzyme catalyzes pyruvate <-> lactate and what other substrates are needed?
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Lactate dehydrogenase; NADH when going to lactate, NAD+ when going to pyruvate
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What is pyruvate converted to before it enters the citric acid cycle?
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acetyl coA
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What catalyzes the reaction pyruvate -> acetyl coA and what are the other reactants and products?
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pyruvate dehydrogenase complex; NAD+ + CoASH -> NADH + H+ + CO2
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What inhibits PDH?
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NADH, acetyl coA
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what cofactors do PDH need?
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thiamine and niacin
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What are the two types of mitochondrial populations in skeletal muscle?
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subsarcolemmal and between myofibrils
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What are the reactions of the citric acid cycle?
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pyruvate -> Acetyl coA + OAA -> citrate -> a-ketoglutarate -> succinyl-coA -> succinate -> fumarate -> OAA
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What are the high energy inputs and outputs of glycolysis?
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2 ATPs in; 4 ATPs and 2 NADH out
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what are the high energy outputs of the citric acid cycle?
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4NADH, 1GTP, 1FADH2
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Which reactions in the citric acid cycle releases CO2?
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pyruvate -> acetyl coA
citrate -> a-ketoglutarate a-ketoglutarate -> succinyl-coA |
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Which reactions in the citric acid cycle produce NADH?
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pyruvate -> acetyl coA
citrate -> a-ketoglutarate a-ketoglutarate -> succinyl-coA |
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Which reaction in the citric acid cycle produces GTP?
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succinyl-coA -> Succinate
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Which reaction in the citric acid cycle produces FADH2?
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succinate -> fumarate
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What form of PDH is the active form?
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unphosphorylated
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Where does complex I in the electron transport chain accept electrons from?
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NADH
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What does complex II in the electron transport chain accept electrons from?
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FADH2
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What shuttles electrons from complex I/II to III
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CoQ
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What shuttles electrons from complex III to IV?
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cytochrome c
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Which direction do protons flow through ATP synthase?
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from intermembrane space into mitochondrial matrix
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What kind of environment favors superoxide formation?
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high proton motive force (slow electron flow)
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Where does gluconeogenesis start?
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inside mitochondrial matrix
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Which reactions of gluconeogenesis occur inside the mitochondrial matrix?
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pyruvate -> OAA -> malate
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What is the energy source for the reaction pyruvate -> OAA in gluconeogenesis?
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ATP
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What is the energy source for the reaction OAA -> malate in gluconeogenesis?
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NADH
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Which enzyme catalyzes the reaction pyruvate -> OAA?
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pyruvate carboxylate
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Which enzyme catalyzes the reaction OAA -> PEP; where is it located; and what is the energy source for the reaction?
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phosphoenolpyruvate carboxykinase (PEPCK); in cytoplasm; GTP
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Which enzyme catalyzes the reaction F1,6P -> F6P and what modulates it?
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fructose 1,6 bisphosphatase; F2,6P inhibits it
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Where does energy for gluconeogenesis come from?
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fatty acids
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Which organs have G6Phosphatase?
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liver and kidney
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Which enzyme catalyzes the reaction glycogen -> glucose 1P
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glycogen phosphorylase
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What molecules in skeletal muscle activate glycogen phosphorylase?
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Ca and AMP
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Which enzyme catalyzes the reaction G1P <-> G6P
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phosphoglucomutase
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Name the reaction steps from glucose to glycogen?
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glucose <-> G6P <-> G1P -> UDP-glucose -> glycogen
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what enzyme catalyzes the reaction UDG-glucose -> glycogen?
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glycogen synthase
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What form is glycogen phosphorylase and glycogen synthase active?
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glycogen phosphorylase = -P
glycogen synthase = not -P |
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Which molecules promote the formation of inactive PDH-P by protein kinase?
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ATP, NADH, Acetyl CoA
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Which molecules inhibit the formation of inactive PDH-P by protein kinase?
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pyruvate
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What energy molecules and how many do you get from one G6P through the pentose shunt?
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2 NADPH
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What is the key regulated step of the pentose shunt and which enzyme catalyzes it?
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G6P -> gluconolactone; G6PD
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What does mitochondrial pyruvate need to be converted to in order to be transferred outside of the mitochondria for gluconeogenesis?
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OAA then malate
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Which enzyme converts pyruvate to OAA for gluconeogenesis?
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pyruvate carboxylate
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What enzyme converts OAA to PEP and where is it located?
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PEPCK in cytosol
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What is the blood drainage of the pancrease?
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hepatic portal
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What do PP cells in the islet of langerhans make?
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pancreatic polypeptide
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What comprises proinsulin?
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C-peptide and insulin
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What does epinephrine do to insulin secretion?
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inhibits it
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What triggers insulin release from beta cells (pathway)?
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increased glucose -> ATP from glycolysis -| K-ATP channels -> depolarization of cell membrane -> increased Ca via L-type Ca channels -> exocytosis of vesicles containing insulin
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Which enzymes do insulin promote to upregulate fatty acid synthesis?
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PDH and acetyl coA carboxylase
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Which enzyme in adipose tissue is inhibited by insulin and what does it do?
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hormone sensitive lipase; breaks our TAGs
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What type of receptor is the insulin receptor?
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EGF family of tyrosine kinase
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What is the key transducer of insulin signaling?
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insulin receptor substrate
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What are the two results of insulin signaling via PI-3K?
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1) inactivates GSK-3 so glycogen synthase stays in active form
2) GLUT4 transporters transferred to PM from vesicles |
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What is the inactive form of GSK-3?
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phosphorylated
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What enzyme in adipose tissue is activated by insulin and what does it do?
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lipoprotein lipase; enables transcytosis of LDL into adipocytes
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What are the two main insulin signal transduction pathways?
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PI-3K and GRB-2 -> MAPK
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What kind of glucose transporter exists in beta cells?
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GLUT2
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What are the actions of glucagon?
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1) promotes beta oxidation: increase acetyl coA carboxylase, inhibits PDH
2) promotes pyruvate carboxylase 3) increase glycogen phosphorylase |
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What is the main glucagon signaling pathway to get glycogenolysis?
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Gs -> cAMP -> PKA -> phosphorylase kinase -> glycogen phosphorylase
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What are the test result limits for diagnosing diabetes?
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fasting >126, oral GTT >200, HbA1C > 6.5
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Which cells are responsible for type 1 DM?
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T cells
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What is the genetic risk of developing type 1 DM if you have a first degree relative with it?
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1:20
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What are common illnesses associated with T1DM?
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Thyroid autoimmunity, celiac, Addison's
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What is the diagnostic criteria for LADA?
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1) 30-70 years at diagnosis
2) at least 6 months non-insulin requiring 3) presence of autoantibodies |
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Does oral insulin prevent type 1 diabetes?
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In kids with FDR + moderate autoantibody titers = 4-5 yr delay
In kids with FDR + high autoantibody = 10 yr delay |
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A single course of what drug at diagnosis of T1DM improves insulin secretion for 2 yrs?
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anti-CD3
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What are the criteria to screen for diabetes?
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>45 yrs, fHx, HTN, dyslipidemia, central obesity, gestational, birthweight >9lbs, ethinicity
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How is an insulin clamp measured?
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infuse insulin until suppress hepatic glucose out and then until all glucose goes to muscle and see how much glucose needs to be replaced
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What is the mechanism of action of sulfonylureas?
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close ATP sensitive K channels in beta cells
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Name some examples of sulfonylureas
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glyburide, glipizide, glimepiride
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What are some negatives to using sulfonylureas?
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increase insulin even when not high, loses effectiveness in long term, weight gain
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What is the mechanism of action of metformin?
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potentiates insulin effect on decreasing hepatic glucose production
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Side effects of metformin
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lactic acidosis, GI (titrate dose when starting)
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Mechanism of thiazolidinediones
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ligands for PPAR-gamma, stimulates adiponectin production/action
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Name examples of TZDs
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pioglitazone, rosiglitazone
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Side effects of TZDs
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worsening of CHF, risk of bladder cancer w >1 yr use
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What is the incretin effect and how is it different in T2 diabetics?
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insulin from oral glucose - insulin from iv glucose
lower in T2DM |
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Name the incretins and which is targeted for therapy
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GLP-1 (therapy) and GIP
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What cells create GLP-1?
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L cells in ileum
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What enzyme inactivates GLP-1?
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DPP-4
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Mech of exenatide
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GLP1 receptor agonist
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Mech of liraglutide
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GLP1 analogue
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Mech of sitagliptin, saxagliptin, linagliptin
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DPP4 inhibitors
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Function of amylins
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decrease glucagon, decrease gastric emptying, decrease appetite
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Name an amylin analogue
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pramlintide
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Compare effectiveness at lowering A1c levels of different classes of drugs
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insulin > metformin = sulfonylureas > everything else
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glycemic targets for diabetics
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fasting: 70-130, 2 hr post meal: <180, HbA1c: <7.0
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name rapid acting insulins and onset of action
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humalog, novolog, glulisine; 15 min
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name intermediate acting insulins and onset of action
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humulin, novolin; 30-60 min
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Name long acting insulins and onset of action
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detemir, glargine; 1.5 - 3hr
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Why should we avoid rapid improvement of glycemic control in certain patients?
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worsen retinopathy
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Insulin therapy is always first line in type 2 DM when...
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weight loss, fasting >250, random >300, DKA
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kCal/g of carbs, proteins, fats
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carbs = 4, proteins = 4, fats = 9
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How does fructose contribute to fatty acid synthesis?
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bypasses PFK and goes straight to pyruvate in glycolysis
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What does acetyl coA need to be converted to before it leaves the mitochondria to participate in fatty acid synthesis?
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citrate
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What are the steps in fatty acid synthesis that occur in the cytosol?
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citrate -> acetyl coA
acetyl coA -> malonyl coA malonyl coA -> palmitic acid |
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Elongation and desaturation of FAs occurs in which organelle?
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ER
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What configuration are unsaturated bonds in FAs?
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cis
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Name the essential FAs
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linoleic and linolenic (omega-3 and -6)
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Which enzyme catalyzes citrate -> acetyl coA?
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citrate lyase
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Which enzyme catalyzes acetyl coA -> malonyl coA?
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acetyl coA carboxylase
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Which enzyme catalyzes malonyl coA -> palmitic acid?
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FA synthase
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What regulates acetyl coA carboxylase and how?
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polymerization: citrate promotes, long chain FAs inhibits
Phos: glucagon promotes phos inactive, insulin promotes dephos active |
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Where do the first 2 Cs on FAs come from and all subsequent Cs?
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acetyl coA first, then malonyl coA
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What provides the energy for reduction steps in FA synthesis?
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NADPH
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How are long chain FAs tranported from the cytosol into the liver cell mytochondria in order to undergo beta oxidation?
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Carnitine palmitoyl transferase (CPT-1) converts acyl-coA to acyl-carnitine which can freely flow across membranes
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what compound inhibits CPT1?
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malonyl coA
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What are the final products of beta oxidation?
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Acetyl coA, NADH, FADH2
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What is the active form of hormone sensitive lipase?
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phos
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what results from carnitine deficiency and in addition to inborn error, what group of people are likely to get this deficiency?
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massive TAG deposits in liver, strict vegetarians
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second most common cause of enzyme deficiency-linked hemolytic anemia
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pyruvate kinase
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Oligomycin inhibits what?
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ATP synthesis
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what coenzyme is used for pyruvate carboxylate?
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biotin
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which vitamins are essential for PDH function?
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niacin, riboflavin, thiamin, pantothenate coenzyme A
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Biotin deficiency results in build up of what?
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pyruvate
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how does blood flow in the islet of langerhans?
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from core to periphery
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Describe the adrenergic effect on insulin secretion
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alpha - decreases
beta - (after long term and high doses epi) increases |
