Turco 6 Flashcards
Things that use glucose as primary source of energy
Kidney, testis, RBCs, embryonic tissue
Under starvation, MUST
Drink water because of ketone bodies
SOurces of glucose
Diet
Gluconeogenesis
Glycogen
Gluconeogenesis occurs in
Liver (and a little in kidney)
Sources of carbon for glucose
Lac/Pyr
Glycerol (from TG breakdown, but NOT FA)
Glucogenic AAs - all but leucine and lysine
Bypass rxn 1 + 2
Pyruvate carboxylase and PEP carboxykinase
Pyruvate carboxylase rxn
Takes pyr to OAA (ABC enzyme)…regulated by acetyl-CoA (obligate activator)
ABC enzymes
Propionyl carboxylase
pyruvate carboxylase
acetyl-CoA carboxylase
PEP carboxykinase rxn
OAA to PEP…gives off CO2 and uses GTP
Increased by glucagon and cortisol at genomic level
PEP carboxykinase rxn equilibrium
CO2 produced is breathed out and drvies formation of products
Bypass reaction 2
Fructose-1,6-bisphosphatase takes F-1,6-P to F-6-P and Pi
Regulated allosterically by F2,6P (turns off)
Turned on by ATP
Bypass reaction 3
Glucose-6-phosphatase
G-6-P to glucose and Pi
Metformin
Used for type 2 diabetes by inhibiting gluconeogenesis
PDH
Pyruvate dehydrogenase produces CO2
Takes pyruvate to AcCoA…decreased by AcCoA and increased by thiamine (cofactor)
Pyruvate can come from
Lactate/alanine/glycolysis
TG mobilization/FA-beta oxidation effects of gluconeo and glycolysis
Increases ATP which activates F-1,6-bisphosphatase and inactivates PFK1
Glycerol can form Glyceraldehyde-3-phosphate that can bypass first set of bypass rxns
FA-beta oxidation produces AcCoA that activate pyruvate carboxylase and inhibits PDH
Glucagon effect on glycolysis/gluconeogenesis
Glucagon will decrease PFK2 activity which will decrease F,2,6P which will decrease PFK1 activity
Glucagon increases activity of PEP carboxykinase
INsulin effect on glycolysis/gluconeogenesis
Insulin activates glucokinase and PFK2
Liver reserves of glycogen have enough storage for ____ hours
12 hours resting
1 hour exercising
Why do glycogenolysis and gluconeogenesis occur simultaneously?
Gluconeogenesis is regulated on a genomic level so it takes a long time…if you waited for all of glycogen stores to be depleted, would have period of time where you would not be able to make any glucose
Fasting effects
Decrease glycogen synthesis and increase breakdown via phosphorylation Decrease glycolysis because of increased ATP (from FA) and decreased F2,6P (because of decreased insulin) Increase gluconeogenesis (obligate, allosteric, hormonal regulation)
Liver energy source during fasting
FA
Glucose reserved from brain and other important cells
Peroxisome major functions
Oxidation of VLCFA (generates H2O2)
Oxidation of branched chain/hydroxylated FAs (into phytanic acid)
Conversion of cholesterol to bile acids
Synthesis of plasmalogens (ether lipids)
VLCFA oxidation
Undergoes alpha oxidation
Attached to CoA and brought into peroxisome…inside, converted to SCFA-CoA and MCFA-CoA (FADH2 produced is converted to H2O2)…SCFA attached to carnitine and brought into mitochondria…inside mitochondria, CAT 2 removes the carnitine and undergoes Beta-oxidation just as any other would
Oxidase and catalase
Oxidase forms H2O2 from O2 using FADH2
Catalase takes H2O2 to H2O
Zellweger syndrome
Defect in peroxisome biogenesis
Accumulation of VLCFA and hydroxylated/branched FAs
Defects primarily in liver and brain (incorporated into myelin sheaths)
Adrenoleukodystrophy
Defect in FA trasnporters in peroxisome membrane
X-linked rec
Defect primarily in brain (myelin sheaths)
Refsum dz
Defect in alpha oxidation of phyanoyl-CoA
Control with low phytanoic acid diet
Neuro probs
Tx of peroxisomal disorders
Fibrates - PPAR alpha
Thiazolidinediones - PPAR gamma
Both turn on peroxisomes
Reye’s Syndrome
Associated iwht fatty acid oxidation defect…can be cause of SCID
Will find fatty droplets in the liver
Vomiting, mental stauts change, seizures
No cirrhosis, just TG accumulation
Aspirin metabolites
Decrease Beta-oxidation of fatty acids…why you can’t give them with Reye’s Dz
Hemosiderin deposits
Indicate iron problem
Mallory bodies
Seen in alcoholic cirrhosis
Why should you not exercise then drink alcohol?
Lactic acid will leave muscle and go to liver where converted back to pyruvate using NAD
Alcohol metabolism reuqires NAD…if alcohol metabolism using NAD, then lactate concentration will increase and pH will drop
Alcohol metabolism
Alcohol converted to acetaldehyde using alcohol dehydrogenase
Acetaldehyde converted t oacetic acid using acetaldehyde dehydrogenase
Both use NAD
Acetaldehyde causes damage
Femopizole
Inhibits alcohol dehydrogenase
Tx for methanol or ethylene glycol poisoninig
Methanol accumulates and is excreted
Disulfiram
Inhibits acetaldehyde dehydrogenase which causes acetaldehyde to accumulate and makes patient sick
Acetaldehyde dehydrogenase deficiency ethnic
Asians from pacific rim
Exercise induced hypoglycemia effect
GLUT 4 transported to membrane of monocytes due to increased concentrations of AMP…this causes hypoglycemia in the blood
Cramping/muscle pain caused by
Inadequate delivery of oxygen
Ketotic hypoglycemia
Hypoglycemia with ketonuria and ketonemia
This means there is a problem with protein catabolism
Error in FA metabolism leads to
Hypoketosis
Hypoglycemia without ketosis (with low blood pH)
Answer could be increased circulating levels of insulin…would cause blood glucose to decrease
Increased A1C seen
Chronically
