Biochem Exam 3 (Clinical Coorelates)

Front 1

Pyruvate Dehydrogenase Deficiency causes elevated serum levels of what?

Back 1

lactate, pyruvate & alanine

Front 2

The elevated serum levels in pyruvate dehydrogenase deficiency leads to what?

Back 2

chronic lactic acidosis, which leads to decreased oxygen levels causing the patient to go into shock.

Front 3

Where is Fumerase deficiency found?

Back 3

mitochondria and cytosol of tissues

Front 4

What is Fumerase Defiency?

Back 4

An autosomal recessive disease which is characterized by:
*Severe neurological impairment
*Encephalopyopathy
*Dystonia development shortly after birth
*High levels of fumurate,a-ketoglutartate, citrate & malate in urine

Front 5

What is cyanide poisoning?

Back 5

Cyanide inhibits the terminal step of the mitochondrial electron transport chain, resulting in the cessation of mitochondrial respiration and energy production. The cell soon dies.

Front 6

How does cyanide kill the person?

Back 6

Tissue death (particularly in the CNS) resulting from anoxia

Front 7

How do you stop cyanide poisoning?

Back 7

Administration of nitrates that convert hemoglobin to methemoglobin, which competes with cyochrome a3 for the cyanide substrate.

Front 8

What is Leber’s Hereditary Optic Neuropathy (LHON)?

Back 8

The first mitochondrial disease understood at the molecular level. It is maternally inherited and effects the CNS including the optic nerves.

Front 9

What does Leber’s Hereditary Optic Neuropathy (LHON) cause?

Back 9

lower activity of NADH:ubiquinone oxidoreductase resulting in blindness (in smaller amounts) and movement disorder, impaired speech & mental retardation (in larger amounts)

Front 10

What are the two types of Mitochondrial Myopathies from Mutations in tRNA Genes?

Back 10

*MERRF (myoclonic epilepsy & ragged red fibers)

*MELAS (mitochondrial encephalopathy, lactic acidosis & stroke-like activity)

Front 11

What is MERRF?

Back 11

myoclonic epilepsy & ragged red fibers - caused by the mutation in the tRNA gene for Lysine. Symptoms include: myoclonus, ataxia, generalized seizures & myopathy. Skeletal muscles have abnormally shaped mitos with paracrystalline structures – look like ragged red fibers. Decrease cytochrome c oxidase activity (ETC)

Front 12

What is MELAS?

Back 12

mitochondrial encephalopathy, lactic acidosis & stroke-like activity - caused by a mutation in the tRNA gene for Leucine

Skeletal muscles appear like ragged red fibers BUT retain cytochrome c oxidase activity

Severity depends on amt of mutation:
>85% mutated DNA – severe CNS symptoms
5-30% mutated DNA – present with maternally inherited diabetes mellitus & deafness.

Front 13

What is a missense mutation in cytochrome b?

Back 13

Glycine is replaced by a larger charged molecule (such as Ser, Glu, or Asp).

Various conditions result, ranging from exercise intolerance to hypertrophic cardiomyopathy

Front 14

What is a nonsense (deletion) mutation in cytochrome b?

Back 14

truncation of cytochrome b and deletions of 4 to 24 base pairs of mtDNA.

Causes severe exercise intolerance, lactic acidosis in resting state, and some myglobinuria.

Front 15

What are missense & nonsense/deletion mutations detected in cytochrome b?

Back 15

Only expressed in muscle tissues (may be somatic mutations occurring during germ-layer differentiation of myogenic stem cells.)

Not maternally inherited.

Front 16

What causes ischemia?

Back 16

occlusion of major coronary artery during myocardial infarction

Front 17

What results from ischemia?

Back 17

inhibition of mito ETC with accompanying decrease in intracellular levels of ATP & creatine phosphate.

The decreased ATP production increases anaerobic glycolysis resulting in build up of lactic acid in the cytosol, leading to a lowered pH.

Front 18

What causes damage from ischemia?

Back 18

Damage to affected tissues is related to the reintroduction of O2 called “reperfusion” (not the ischemia itself)

Reperfusion can lead to activation of leukocytes, which causes additional tissue damage

Front 19

Injuries to myocardium due to ischemia/reperfusion

Back 19

Contractile dysfunction, arrhythmias & irreversible myocyte damage.

Front 20

What does acute alcohol intoxication cause?

Back 20

increases in sensitivity to the general depressant effects of barbiturates and can be fatal – even at normal Rx levels.

Front 21

What does ethanol inhibit?

Back 21

metabolism of barituates – prolonging their time in the body

Front 22

What is arsenate?

Back 22

The pentavalent form of arsenic (less poisonous).

Arsenate can substitute for Pi and decrease ATP synthesis and compete for Pi binding sites on enzymes.

Formation of unsaturable arsenate esters results.

Front 23

What is arsenite?

Back 23

'Arsenic poisoning' - forms a stable complex with enzyme bound lipoic acid, resulting in the inhibition of enzymes the require the lipoic acid.

Enzymes affected includes: pyruvate DH, a-ketoglutarate DH, & branched-chain a-keto acid DH

Front 24

How is aresenite poisoning diagnosed?

Back 24

Diagnosed by determining arsenite concentration in hair and nails.
*Normal levels: 0.5mg/kg hair
*Lethal levels: 500mg/kg hair

Front 25

What is fructose intolerance?

Back 25

Deficiency in adolase-B which splits fructose during glycolysis. What results is a build up of fructose and a decrease in ATP. The cells soon swell due to osmotic lysis.

Front 26

What is diabetes mellitus?

Back 26

A chronic disease characterized by derangement in carbohydrates, fat, and protein metabolism.

Glucose uptake in adipose and muscle tissue is decreased due to a lack of insulin.

Front 27

What is lactic acidosis?

Back 27

The most frequent form of metabolic acidosis, characterized by an increase in lactic acid (>5 mm) and a decrease in blood pH.

It can be caused by an overproduction, underutilization (or both) of lactate

Front 28

How is lactic acidosis treated?

Back 28

Bicarbonate administered to help regulate acidosis due to increase in lactic acid levels, but important to find root cause of lactate overproduction/underutilization.

Front 29

What is malignant hyperthermia?

Back 29

Dominant genetic disease that is characterized by an increase in core body temperature following exposure to halothane. Causes include: metabolic & respiratory acidosis, hyperkalemia & muscle rigidity

Front 30

How is malignant hyperthermia treated?

Back 30

immediate ice packing of body and drug administration to combat acidosis; dantrolene

Front 31

What is Porcine Stress Syndrome?

Back 31

Pigs under stress that are exposed to halothane result in meat that is “pickled” (pale, watery, & very low pH).

Front 32

What causes the physiological response to halothane?

Back 32

An abnormal ryanodine receptor in sacroplasmic reticulum of skeletal muscle cells

Front 33

What happens to the ryanodine receptor as it is exposed to halothane

Back 33

increased Ca+2 released and uncontrolled stimulation of heat-producing processes occur including: ATPase, Glycogenolysis, Glycolysis, cyclic uptake and release of Ca+2

Most cells irreversibly damaged due to heat production, lactic acidosis & ATP loss

Front 34

What is angina pectoris?

Back 34

(strangling pain in chest); associated with reversible myocardial ischemia

Due to imbalance of supply & demand for blood – caused by narrowing of coronary arteries (atherosclerosis or spasm).

Attacks occur upon exertion; last 1 to 15 minutes – resolved by rest or death.

Front 35

What is a myocardial infarction?

Back 35

occurs if ischemia persists and causes sever damage to heart muscle; clots typically form in narrowed arteries totally blocking them – tissue death and increased pain occurs.

Front 36

What can be used to treat myocardial infarctions and angina pectoris?

Back 36

1) Nitoglycerin/Nitrates - breaks down into NO, causing smooth muscle relaxation and venodilation throughout the body.

2) Ca+2 channel blockers (vasodilators)

3) β-adrenergic blockers (prevent increased O2 consumption by heart)

4) Coronary artery bypass operation

Front 37

What is muchopolysaccharidoses?

Back 37

Genetic disorders characterized by excessive accumulation of oligosaccharides & proteoglycans.

Caused by deficiency of one or more lysosomal hydrolases that degrade dermatan and/or heparin sulfate. 1 in 30,000 births.

Front 38

What are four examples of muchopolysaccharidoses?

Back 38

Hurler's syndrome, Sanfilippo’s Syndrome, Hunter's syndrome, and Multiple sufatase deficiency (MSD)

Front 39

What is heparin?

Back 39

a naturally occurring sulfated glycosaminoglycan; reduces clotting tendency through binding to antithrombin III (inhibitor of coagulation process)

Front 40

What occurs if you are deficient in antithrombin III?

Back 40

increased risk of thrombosis in veins and resistance to action of heparin

Front 41

What do RBCs depend upon for ATP?

Back 41

glycolysis, without ATP, the swell bursts and dies due to NA/K pump

Front 42

What is hemolytic anemia?

Back 42

excessive RBC destruction caused by deficiency in Pyruvate Kinase (PK) resulting in a limited flux through the glycolytic process.

Front 43

Neonates have ____ susceptibility to hypoglycemia compared to adults

Back 43

increased, due to brain/body size.

Front 44

What causes hypoglycemia in a premature infant?

Back 44

The brain is largely disproportional to body, using a larger amount of glucose than normal, brain almost completely dependent on glucose from liver glycogenolysis and gluconeogensis

Front 45

How does ethanol affect hepatic gluconeogenesis.

Back 45

Alcohol consumption can inhibit gluconeogenesis in the liver, resutling in hypoglycemia

Front 46

What are Glycogen Storage Diseases (GSD)?

Back 46

inherited diseases involving defects in one or more of the enzymes involved in synthesis or degradation of glycogen.

Liver is most affected, but heart and muscle glycogen metabolism can also be defective

Front 47

What is Von Gierke’s Disease?

Back 47

Type I GSD - the most common GSD that results from a deficiency of glucose 6-phosphatase in the liver, kidneys, and intestinal mucosa.

Front 48

What are the manisfestations of Von Gierke's Disease?

Back 48

fasting hypoglycemia, lactic academia, hyperlipidemia & hyperuricemia with gouty arthritis

Front 49

How is Von Gierke's Disease treated?

Back 49

diminished symptoms by eating carbohydrates throughout the day

Front 50

What is Pomp's Disease?

Back 50

Type II GSD - absence of a-1,4-glucosidase (or acid maltase) normally found in lysosomes which leads to increased glycogen in lysosomes throughout body; lysosomes can not hydrolyze glycogen and become defective in their other functions because of the buildup

Front 51

What is Cori's Disease?

Back 51

Type III GSD - by deficiency in glycogen debranching enzyme resulting in glycogen accumulates because only outer branches can be removed by phosphorylase. Hepatomegaly occurs, but diminishes with age

Front 52

What is McArdle's Disease?

Back 52

Type V GSD - absence of muscle phosphorylase, results in muscle cramps and tissue death due to a lack of ATP and an accumulation of glycogen.

Front 53

What is Wernicke-Korsakoff Syndrome?

Back 53

deficiency or genetic variants of transketolase which results in mental disorder with memory loss & partial paralysis.