Week 1 Diseases
Chapter 8: Glycolysis
oLactic Acidosis- lactate in plasma usually because of a collapse in the CNS
oAldolase deficiency (fructose intolerance)- causes lethargy, vomiting, liver damage,
hyperbilirubinemia, hypoglycemia, hyperuricemia, renal proximal tubule defect.
oPyruvate kinase deficiency (PKD)
oAutosomal recessive disorder
o 2,3. Biphosphoglycerate + O2 affinity of Hb
oAbnormal RBCs as echinocytes “Burr cells” that have spikes on them which are easily destroyed
in the spleen; many require partial splenectomy to stop so much RBC destruction.
oLoss of Na/K pump causing swelling, rigidity, osmatic fragility, lysis
oAbsence of Heinz bodies which are inclusions in RBCs that are composed on denatured
hemoglobin.
oLactose intolerance, allergy to lactose from ingested milk. Allergy in the intestines
oCauses diarrhea, bloating, abdominal pain
oGalactosemia, “galactose in blood”
oAutosomal recessive
o plasma galactose because the body can’t process and produce energy from galactose
oLethargy, vomiting, hypotonia, retardation, cataracts, and failure to thrive.
oClassic galactosemia is more severe
oGlucokinase deficiency, when enzyme glucokinase cannot sensor glucose in the blood.
oInactivating mutations cause a rare form of diabetes called MODY2
oCharacterized by. Impaired insulin secretion and hyperglycemia.
oVibro cholerae Bordetella pertussis ((cholera) and whooping cough) causes inappropriate inactivation of
adenylyl cyclase through covalent modification of difference. G proteins.
oIn cholera, the activity of is inhibited in intestinal walls.GTPase Gas
oIn whooping cough, is inactivated in the reparatory tract.Gai
oPDC Deficiency
oReview summary sheet.
oRemember PDC-deficiency is x-linked dominant.
Chapter 9: TCA cycle
oTPP or niacin deficiencies cause CNS issues because brain cells are unable to produce sufficient ATP if
PDHC is inactive
oPDC deficiency and. Wernicke-Korsakoff encephalopathy-psychosis results from TPP
deficiency.
oSymptoms include ataxia, nystagmus (involuntary eye movements), memory loss, cerebral
hemorrhage, psychosis, ketosis.
oLactic acidosis
oDue to PDC deficiency which leads to insufficient production of acetyl-CoA, so the pyruvate
converts to lactate via LDH
oLeigh Syndrome (necrotic encephalomyelopathy)
oDue to defects in ATP production because of a mutation in PDHC, ETC, or ATP synthase genes.
Chapter 10: Gluconeogenesis
oGlycogen Storage Diseases la and lb are caused by deficiencies in phosphatase and translocase.
oCharacterized by severe fasting hypoglycemia.
oChronic hypoglycemia is accompanied by in ketone bodies
Chapter 11: Glycogenesis and degradation
oMcArdle Disease (Skeletal Muscle Glycogen or Deficiency)Phosphorylase Myophosphorylase
Week 1 Diseases
oSkeletal muscle affected; liver enzyme normal
oTemporary weakness and cramping of skeletal muscle after exercise
oNo rise in blood lactate during strenuous exercise
oRelative benign, chronic condition
o glycogen with normal structure in muscle
oDeficiency of the liver isozyme causes with mild fasting hypoglycemiaHers disease
oPompe Disease (lysosomal
(1
4) glucosidase deficiency)
oOnly GSD that is a lysosomal storage disease
oGeneralized but primarily heart, liver, muscle
oExcessive glycogen in the lysosomes
oNormal glycogen structure
oNormal blood sugar levels
oHypotonia, muscle weakness, and massive cardiomegaly (large heart); fatal in infants
oEnzyme replacement therapy
oCori Disease (4:4 transferase and/or Amylo-
(1
6)-glucosidase deficiency)
oFasting hypoglycemia
oAbnormal glycogen structure with four or one glycosyl residues at branch points.
oType 1a: Von Gierke Disease ( deficiency); Type 1b G6P G6Pase Translocase deficiency
oAffects liver and kidneys
oFasting hypoglycemiasevere
oFatty liver
oProgressive renal disease
oGrowth retardation and delayed puberty
oLactic acidemia, hyperlipidemia, hyperuricemia
oNormal glycogen structure; glycogen stored
oType 1b has neutropenia and recurrent infections
oTreatment: nocturnal gastric infusions of glucose.
Chapter 23: Metabolic Effects of Insulin and Glucagon
oHypoglycemia is characterized by CNS symptoms (confusion, aberrant behavior, coma) and a low blood
glucose (<50mg/dl). It prompts immediate secretion of glucagon, Epinephrine, and Norepinephrine, and
decreased secretion of insulin.
oInsulin-induced
Seen in diabetic patients. Mild hypoglycemia in fully conscious patients is treated by
administration of a carb. In unconscious patients, a glucagon is given subcutaneously or.
Muscularly.
oPostprandial
Exaggerated insulin release following a meal, prompting transient hypoglycemia with
mild adrenergic symptoms. The plasma glucose level returns to normal even if the patient
is not fed. The only treatment is that the patient eats frequent small meals that 3 large
ones.
oFasting
Due to low glucose production. Usually seen in patients with hepatocellular damage or
adrenal deficiency or in fasting individuals who have consumed large amounts of ethanol.
Or it could occur by increase used of glucose by peripheral tissue because of the
overproduction of insulin by rare pancreatic tumors.
oAlcohol-induced
Week 1 Diseases
The metabolism of ethanol results in a massive increase in the concentration of cytosolic
NADH in the liver which causes the intermediates of gluconeogenesis to be diverted into
alternate reaction pathways resulting in decreased synthesis of glucose.
