Exam 3 Clinical Correlates

Question 1

Glycolysis defects

Answer 1

• pyruvate kinase deficiency
  -galactosemia
  -fructose and galactose mutations
  -essential Fructossura
  -hereditary fructose intolerance

Question 2

Pyruvate Kinase Deficiency

Answer 2

-lack of Atp –> hemolytic anemia
-jaundice

Question 3

Fructose and galactose mutations

Answer 3

-recessive inheritance
-failure to thrive
-multi-organ involvement triggered by offending food

Question 4

Essential Fructosuria

Answer 4

-fructokinase deficiency does not enter the liver
-excessive fructose in urine

Question 5

Hereditary fructose intolerance

Answer 5

-Aldolase B deficiency
-FIP trapped in liver
-depletes phosphate
-inhibits glycogen mobilization (hypoglycemia)
-liver damage

Question 6

Galactosemia

Answer 6

-galactose 1 phosphate uridyltransferase deficiency
-galactose 1 phosphates accululate in liver, cns, kidney (diarrhea, jaundice, vomiting)
-UDP galactose epimerase deficiency
-galactokinase deficiency

Question 7

Mitochondrial effects

Answer 7

-DNP
-MERF
-MELAS
-combined oxidative phos. deficiency

Question 8

DNP

Answer 8

-uncoupling
-collapses proton gradient and bypasses ATP synthase
-hyperthermia, tachycardia, diaphoresis, death

Question 9

MERF

Answer 9

-point mutation in trna for lysine
-myoclonus
-ataxia
-seizures

Question 10

MELAS

Answer 10

-mutation in trna for leucine
-mitochondrial myopathy enoephalopathy
-lactic acidosis
-stroke like episodes

Question 11

Combined oxidative phos. deficiency

Answer 11

1. mutation in mitochondrial elongation
2. mutation in ribosomal protein s16
   -metabolic acidosis
   -microcephaly
   -liver dysfunction
   -growth retardation
   -encephalopathy

Question 12

BeriBeri

Answer 12

-thiamine deficiency
-pain and parathesia
-wet - CHF and peripheral edema
-dry - symmetrical peripherial neuropathy

Question 13

Wernickes encephalopathy

Answer 13

-thiamine deficiency, alcoholism
-mental impairment, cerebellar ataxia, opthalmoplega
-can be treated with thiamine
-can lead to koraskoff which is severe learning defect

Question 14

Chronic lactic acidosis

Answer 14

-pyruvate dehydrogenase deficiency
-severe neuro defects
-mutations in E1

Question 15

Fumarase deficiency

Answer 15

-elevated urine fumarate
-neuro impairment
-lactic acidemia
-dystonia
-encephalopathy

Question 16

Glucogenesis disorder

Answer 16

• ex. F 1,6 BP deficiency
  -pre disposed to fasting hypoglycemia
  -pyruvate/lactate accumulate in blood (metabolic acidosis)
  -liver converts then to fat (fatty liver)

Question 17

PPP disorder

Answer 17

• ex. G6P dehydrogenase deficiency
• predisposed to hemolytic anemia (triggered by radical stress)
  -cause jaundice and enlarged spleen
  -G6P = x linked and triggered by h202

Question 18

Glycogen storage

Answer 18

-GSD 1/ VonGierke
-GSD 2 - Pompe
- GSD V = Mcardles

Question 19

GSD 1/ VonGierke

Answer 19

-affects the liver –> cant release glucose during fasting
-fasting hypoglycemia
-enlarged liver
-metabolic acidosis (lactate accumulates)

Question 20

GSD 2 - Pompe

Answer 20

-lysosomal alpha glucokinase defect
-lysosomal storage disease
-enlarged heart and liver
-affects all tissues

Question 21

GSD V = Mcardles

Answer 21

-muscle glycogen phosphorylase deficit
-muscle cant mobilize glycogen
-exercise intolerance
cannot produce lactate

Question 22

GAG disorders

Answer 22

-Hunter
-Hurler-Schiele
-Sanfilipo
-detect GAGs in urine

Question 23

Hunter disorder

Answer 23

-dermatan and heparan sulfate accumulation
-iduronate sulfate enzyme defects
- x linked
-skeletal abnormalities and intellectual disabilities

Question 24

Hurler-Schiele

Answer 24

–dermatan and heparan sulfate accumulation
-alpha iduronase defects
-skeletal abnormalities and intellectual disabilities

Question 25

Sanfilipo

Answer 25

-heparan sulfate accumulation -mild physical issues -severe intellectual disabilities

Question 26

Acute Stress

Answer 26

- triggers release of epi -binds adrenergic receptors and signals through camp,pka,ca -increase glycogenolysis and glucogenesis in liver -increase glycolysis in muscles

Question 27

Chronic Stress

Answer 27

-increase in cortisol -increase in gluconeogenesis and glycogen synthesis -decrease glucose deposition in adipose tissue -generate insulin resistance

Question 28

Glucoronic acid disorders

Answer 28

-UGT deficiency -Gilbert -Crigler-najjar

Question 29

UGT deficiency

Answer 29

-lead to non-hemolytic jaundice -defects in bilirubin excretion (build up of bilirublin)

Question 30

Gilbert deficiency

Answer 30

-mostly asymptomatic

Question 31

Crigler-najjar

Answer 31

-rare and severe

Question 32

Congenital sucrase/isomaltase deficiency

Answer 32

-affects cleavage of sucrose -diarrhea/gas pain after consuming fruit sugar

Question 33

Lactose non-persistence

Answer 33

-no blood sugar increase -H2 on breath -early adult onset

Question 34

PKA

Answer 34

-activated in response to camp -mediates response to low serum glucose and suddens stress -activates glycogenolysis, fatty acid degradation, gluconeogenesis -supresses -Glycolysis, glycogen synthesis, FA synthesis -outcome = Raises serum glucose, initiates fasting response

Question 35

Akt

Answer 35

-activated in response to PIP3 -mediates response to high serum glucose, growth factors -activates Fatty acid, glycogen and protein synthesis, glucose uptake - suppresses apoptosis - outcome = Lowers serum glucose, stimulates growth

Question 36

PKC

Answer 36

- activated in response to Diacylglycerol, Ca?+ - mediates repsonse to various stimuli - biochemical effects = Various actions, e.g. receptor desensitization, membrane structure changes, smooth muscle contraction - outcome = varies between cell types

Question 37

AMPK

Answer 37

-activated in response to AMP -mediates response to low cellular energy - activates glycogenolysis, glycolysis - suppresses gluconeogenesis, Fatty acid and cholesterol synthesis - outcome = raises cellular ATP