MCM midterm Flashcards
normal fasting blood glucose levels are
70-100mg/dL
what levels of blood glucose are characteristic of hypoglycemia?
what are the symptoms of hypoglycemia
below 60 mg/dL
hunger, sweating, trembling
what levels of blood glucose are characteristic of diabetes?
above 126 mg/dL fasting OR
199 mg/dL 2 hours after receiving dose of 75mg glucose
red blood cells generate ATP from what biochemical process
glycolysis only
describe the pasteur effect and how it relates to cellular energy
aerobic conditions tend to suppress glycolysis via allosteric regulation of glycolytic enzymes by CITRATE and ATP
describe the Warburg effect and how it relates to cellular energy
cancer exhibits high rates of glycolysis despite adequate oxygen. evidence comes from PET scan with fluorodeoxyglucose (FdG)
this 4 carbon sugar alcohol is used as artificial sweetener. low glycemic index, doesn’t fuck up teeth, absorbed and excreted so less flatulence than other sugar alcohols
eryrthritol
this 5 carbon sugar alcohol is used as natural sweetener. low glycemic index, doesn’t promote tooth decay, lower energy content than sucrose at same level of sweetness. no bad aftertaste. very gassy though
xylitol
this sugar alcohol is used by plants and microorganisms to store energy. in medicine it is used to make BBB permeable and to treat head trauma and kidney failure. inhaled solid useful for cystic fibrosis treatment as well.
low glycemic index, tooth friendly sweetener. half as sweet as sucrose, causes flatulence in high doses
mannitol
sugar alcohol is used as a sweetener in chewing gum, toothpaste and mouthwash and as a laxative
sorbitol
explain the formation and treatment of gallstones
bile contains too much cholesterol and too little bile salts.
treated with chenodeoxycholic acid (bile salt) to help restore bile salt pool and in some cases dissolve gallstones
list a few symptoms of gallstones
malabsorption syndromes such as steatorrhea and deficiency in fat soluble vitamins (A,D,E,K)
what kind of environment is necessary for disulfide bond formation?
what effect does glutathione have on disulfide bond formation
oxidizing environment. present in rough ER, but not cytoplasm (due to high glutathione formation). therefore, disulfide bonds are usually present in secreted proteins
describe the daily intake of protein in the average person and how it relates to nitrogen balance
100g of protein consumed daily
400g of protein broken down per day
400g of protein synthesized each day
positive nitrogen balance = nitrogen intake exceeds nitrogen excretion (protein synthesis)
negative nitrogen balance = nitrogen loss exceeds nitrogen intake (protein degradation)
deficiency of this vitamin is marked by night blindness, visual impairment, xerophthalmia and/or keratin in the conjunctiva (Bitot’s)
vitamin A
excess levels of this vitamin result in liver toxicity and joint pain
vitamin A
exposure of infants to this substance leads to cleft palate and heart abnormalities
isotretinoin
list sources of synthetic vitamin A
tretinoin
isotretinoin
the bioactive form of vitamin D is called
calcitriol
this disease is an autoimmune condition resulting in damaged gut mucosa and inflammation as well as malabsorption of nutrients and GI discomfort
Crohn Disease
treated by surgical resection of damaged areas and further prevention via drugs
how does cystic fibrosis can affect the exocrine function of the pancreas?
cystic fibrosis causes mucus plug in pancreatic ducts; check serum amylase and lipase levels to diagnose
describe what can happen in a patient when the endocrine function of their pancreas becomes abberant
diabetes mellitus (insulin/glucagon dysfunction)
excess fat in the stool due to poor digestion or malabsorption is called what? what is a concern of this condition?
steatorrhea
malabsorption of fat soluble vitamins
what are the results of vitamin D deficiency
brittle bones (rickets/osteomalacia) hypocalcemic tetany
what are the results of excess vitamin D
hypercalcemia (dazed, loss of appetite, sarcoidosis)
hypercalicuria
vitamin C is necessary for collagen formation and carnitine function. what results from vitamin C deficiency?
scurvy - purple spots on skin, bruising, spongy/bleeding gums, poor wound healing
the energy released in the removal of the terminal phosphate group of ATP is about equivalent to the energy stored in what other high energy bond?
thioester bond between the thiol group of CoA and carboxylic acids
describe how the kidney regulates blood pH
in acidic conditions, kidney will secrete NH4+ and reabsorb bicarbonate
in basic conditions, kidney will reabsorb less bicarbonate and secrete fewer protons via NH4+
1) what is the function of the gastric proton pump?
2) what is the function of omeprazole
3) what are the sideffects of this drug
1) H+/K+ ATPase (pumps proton into gastric lumen and K+ into the cell)
2) inhibit this proton pump, increasing pH in gut lumen
3) reduced absorption of nutrients, hypochlorhydria, increased sensitivity to food poisoning, reduced efficacy of gastric enzymes
explain why troponin can be useful in diagnosis of MI
troponin is trimer - 3 different subunits (Tn-T, Tn-I, Tn-C)
Tn-I subunit exists in 3 isoforms based on tissue
cTn-I found in cardiac tissue, elevated in blood after MI
certain enzymes, while everpresent in low levels in blood, exist in elevated levels in certain disease states. Elevated levels of alkaline phosphatase indicates what disease?
bone disease
certain enzymes, while everpresent in low levels in blood, exist in elevated levels in certain disease states. Elevated levels of sorbitol dehydrogenase or lactate dehydrogenase (LDH-5) indicate what disease?
obstructive liver disease
certain enzymes, while everpresent in low levels in blood, exist in elevated levels in certain disease states. Elevated levels of acid phosphatase is indicative of what disease?
prostatic cancer
certain enzymes, while everpresent in low levels in blood, exist in elevated levels in certain disease states. Elevated levels of amylase is indicative of what disease?
acute pancreatitis
certain enzymes, while everpresent in low levels in blood, exist in elevated levels in certain disease states. Elevated levels of aldolase and AST are indicative of what disease?
muscular dystrophy
certain enzymes, while everpresent in low levels in blood, exist in elevated levels in certain disease states. Elevated levels of ALT and/or CK-MM isoform of creatine kinase are indicative of what disease?
liver disorder
metalloenzymes are inhibited by what class of substances give an example of one such substance
chelators
EDTA
patient with lead poisoning can be treated using what class of substances?
chelators, specifically Ca-EDTA or Succimer in children
1) GLUT2 exhibits high ______ but low _______
2) GLUT2 operates in which direction
3) GLUT2 operates by what kind of transport
4) explain how GLUT2 can function as glucose sensor in pancreas
1) capacity; affinity
2) bi-directional based on concentration
3) facilitated diffusion
4) rapid influx into pancreatic beta cell; converted to ATP; closure of ATP-dependent K+ channels; membrane depolarization; Ca++ entry into cell; release of insulin (fast); activation of calmodulin and initiation of insulin synthesis
1) describe Fanconi-Bickel syndrome and how it relates to glucose transport
2) what are signs and symptoms as well
3) treatment?
1) autosomal recessive; mutation in GLUT2 of hepatocytes and pancreatic Beta cells; leads to impaired transport of glucose, galactose and fructose
2) failure to thrive, hepatomegaly, tubular nephropathy, and resistant rickets, fasting ketotic hypoglycemia and postprandial hyperglycemia
3) administration of vitamin D and phosphate to treat rickets and uncooked corn starch for the glycemic issues
1) what is the function of mannose-6-phosphate group on hydrolytic glycolipids?
2) what enzyme is responsible for the addition of the mannose-6-phosphate group to the hydrolytic enzyme
3) where does this tagging process take place)
4) deficiency in the enzyme mentioned in 2) results in what disease
1) sorting to the lysosome
2) GlcNac-PT
3) golgi
4) inclusion cell disease
1) phosphatidylserine is normally found in which leaflet of the PM?
2) translocation to the other leaflet is indicative of what?
1) internal
2) apoptosis
list 3 membrane lipids that are usually found in the outer leaflet of PM
phosphatidylcholine
sphingomyelin
glycolipids
list 3 membrane lipids that are usually found in the inner leaflet of PM
phosphatidylinositol
phosphatidylserine
phosphatidylethanolamine
explain Rh factor and hemolytic disease of the newborn
also called D antigen
1st newborn in Rh positive, mother is Rh negative, 2nd fetus, if Rh negative will be attacked by mother’s antibodies that were generated from first pregnancy
treated at 28 weeks pregant with anti-RhD immunoglobulin
what are the class of enzymes called that are capable of translocating lipids from one leaflet of PM to the other
flippases
1) special type of hemolytic anemia characterized by elevated levels of cholesterol in the RBC membrane, resulting in lysis as they pass capillaries of spleen
2) With what other pathology is this special hemolytic anemia associated?
1) spur cell anemia
2) associated with alcoholic cirrhosis
describe the mechanism behind spur cell anemia
build up of cholesterol in the membranes of RBCs, causes lysis of the RBCs as they pass through spleen capillaries
describe how a cell would alter the composition of its PM in response to changes in temperature
cold - add cholesterol or unsaturated fatty acids
text doesn’t specifically say cholesterol just FYI but i think we’ve always heard up until now that cholesterol is the main player in membrane fluidity changes
hartnup disease is the result of what
defect in transporter (kidney and intestines) for nonpolar or neutral amino acids eg TRYPTOPHAN
presents as failure to thrive, nystagmus, intermittent ataxia, tremor, photosensitivity
defect in the transportation of tryptophan, resulting in failure to thrive, nystagmus, intermittent ataxia, tremor, photosensitivity is called
hartnup disease
1) cystinuria is caused by
2) what are the symptoms of cystinuria
1) defect in the transport system responsible for the uptake of dimeric amino acid cystine and dibasic amino acids ARG, LYS and ornithine. (RoCK)
2) formation of cystine crystals or stones in the kidneys which can be identified via positive positive nitroprusside test
inability to properly transport dimeric cystine and dibasic amino acids, arg, lys and ornithine is the result of what disease
cystinuria
oubain and digoxin operate how?
inhinbition of Na+/K+ ATPase on cardiace myocyte PM
leads to increase of cellular NA+ and Ca++; increased Ca++ in sarcoplasm leads to stronger contractions
defects in the CFTR gene results in what?
bulildup of Cl- inside the airway of epithelial cells and in the sweat. Na+ flows into airway cells and water follows. results in thicker mucus, leaves airway prone to bacterial infection (cystic fibrosis)
explain how cystic fibrosis can occur due to an abberant transporter protein
Chloride channel is messed up leading to accumulation of chloride inside the cells of airways and in the sweat. leads to thick mucus and a propensity to develop bacterial infections
the coat protein that is responsible for getting vesicles to move between stacks of golgi apparatus
COP I
coat protein that is responsible for getting vesicles to move from rough ER to the golgi
COP II
1) vesicles are coated by the protein clathrin
clathrin is seen in what pathways?
2) no matter what process is happening clathrin is always located in the same cellular compartment. which compartment is clathrin found in?
1) exocytosis/secretory as well as endocytosis
2) cytoplasm
what is the name of the protein that is responsible for pinching off clathrin coated vesicles
dynamin-1
what is the name of the protein that mediates interaction between receptor protein and clathrin coating protein
adaptin
true or false, all proteins in the lysosome are due to be degraded?
false, some proteins in the lysosome are actually hydrolytic enzymes that are RESPONSIBLE for carrying out the degradation
lysosomes maintain their acidic environment via what structure?
H+ ATPase
what distinguishes a secondary lysosome from a primary lysosome
digestive enzymes are present in a secondary
secondary are heterogeneous
secondary lysosome has active enzymes
what distinguishes a secondary lysosome from a primary lysosome
digestive enzymes are present in a secondary
secondary are heterogeneous
secondary lysosome has active enzymes
what is the underlying pathology present in familial hypercholesteremia?
mechanism of cholesterol uptake is disrupted. elevation of LDL due to abberant LDL receptor
leads to atherosclerotic plaques
what is the function of peroxisomes
synthesis and degradation of hydrogen peroxide
Beta oxidation of long chain fatty acids
bile acid/cholesterol synthesis
detoxify alcohol
zellweger spectrum disorders are characterized by what
defects in the assembly of the peroxisome
no treatment, usually die by one year of age
mitochondria are more or less dynamic in high energy cells?
less dynamic, much more fixed
identify the amino acids that are strictly ketogenic
lysine
leucine
glucogenic amino acids are defined this way because they break down into what?
pyruvate or TCA cycle intermediates
ketogenic amino acids are named this way because they break down into what?
acetyl CoA or acetoacetate
identify the amino acids that break down into pyruvate
tryptophan –> alanine–> pyruvate
threonine–>glycine–>serine –> pyruvate
cystine –> pyruvate
identify the amino acids that break down into oxaloacetate
asparagine
aspartate
identify the amino acids that break down into fumarate
phenylalanine
tyrosine
identify the amino acids that break down into succinyl CoA
Isoleucine
valine
methionine
threonine
identify the amino acids that break down into alpha-ketoglutarate
Glutamine
histidine
arginine
proline
1) all transamination reactions occur via a specific ________ enzyme
2) these enzymes all require ______ as a coenzyme
1) transaminase
2) PLP
1) aminotransferases are normally located in what cellular areas? in what organs?
increase in levels of these enzymes is indicative of diesease. 2) increase in levels of what enzyme is indicative liver disease?
3) increase in levels of what enzyme is indicative of MI?
1) mitochondria/cytoplasm of liver, kidney, intestine and muscle
2) ALT
3) AST
1) what is the function of glutaminase?
2) where would you not expect to find high glutaminase activity?
1) glutamine to glutamate via the loss of ammonium ion
2) brain
what is the function of glutamine synthetase?
conversion of glutamate to glutamine by addition of an ammonium ion
1) homocystinuria can occur as a result of dysfunction or lack of 2 different enzymes or their cofactors. name those two enzymes and their cofactors
1) homocysteine methytransferase/cobalamin(B12)
cystathionine Beta-synthase/PLP(B6)
a patient shows elevated homocysteine levels
what enzyme must be affected or what cofactor must be absent?
cystathionine Beta synthase/PLP (B6)
AND/OR
homocysteine methyltransferase/cobalamin/B12
a patient comes to clinic with piss that smells like burnt maple syrup. he must have a jacked up enzyme. what can you expect to find in his urine?
branched chain amino acids and their derivatives
phenylketonuria is due to a deficiency in what enzyme
phenylalanine hydroxylase
PKU is a disease that involves the inability to convert what amino acid to what product
phenylalanine to tyrosine
name the common derivatives of tryptophan
serotonin–>melatonin
niacin–>NADP
name the common derivatives of serine
acetylcholine
name the common derivatives of tyrosine
dopamine –> norepinephrine –> epinephrine
thyroid hormones
melanin
name the common derivatives of glutamate
GABA
1) describe tyrosine and it relates to the thyroid and Graves disease
2) how can we treat Graves patients
1) thyroglobulin is a protein that is produced by the thyroid that has many tyrosine residues. these tyrosine residues can be iodinated to form monoiodotyrosine or diidotyrosine. these can be combined to form T3 (more potent but less persistant) or T4
2) patients with GRAVES are treated with drugs such as carbimazole and propythiouracil which block the iodination of thryoglobulin
identify the enzyme responsible for iodinating thyrglobulin
thyroperoxidase
ammonia is removed from the muscle in the form of what amino acid?
alanine
the enzyme involved in the rate limiting step of the urea cycle is called what
cabamoyl phosphate synthetase
high protein diets increase urea production
about 20-30% of this urea has a fate other than excretion. what is that fate?
gut bacteria absorb, hydrolyze by bacterial UREASE, salvage and resuse is possible
name the 3 amino acids used in the generation of purine and pyrimidine biosynthesis
aspartate
glutamine
glycine
the primary function of the pentose phosphate pathway is to produce what
NADPH
list the functions of nucleotides
components of cofactors (CoA, FAD, FMN, UDP-Glc, NADPH, NADH)
regulatory roles (cAMP, cGMP)
stabilizing roles
part of important biomolecules (B12)
list the purines in order of least oxidized to most oxidized
adenine
guanine and hypoxanthine
xanthine
uric acid
what is the function of ribonucleotide rieductase
conversion of a ribonucleic acid to a deoxyribonucleic acid
describe the function of mycophenolic acid
immunosuppressant
oxidation of IMP to XMP by IMP DEHYDROGENASE gets blocked, causing a shortage of dGTP in B and T cells. useful in graft vs. host
describe Lesch-Nyhan syndrome
defect in HGPRT enzyme in the purine salvage pathway
Guanine undergoes degradation into urea, furthermore, the PRPP that could’ve been used to salvage that nucleotide is instead used for de novo synthesis, leading to more guanine that can be degraded. leads to hyperuricosuria and hyperuricemia.
the activation of glutamine:PRPP amidotransferase by excess PRPP is the underlying cause of elevated purines
what is acyclovir and how does it carry out its intended medical function
looks like guanine but isn’t guanine. viral THYMIDINE KINASE has higher affinity for the acyclovir than does the human thymidine kinase. because of this viral thymidine kinase will incorporate the acyclovir into the viral DNA and the lack of 3’ hydroxyl group leads to termination of replication
what is the enzyme of interest in the acyclovir situation
thymidine kinase
the pyrimidine ring is synthesized from what two substrates
carbamoyl phosphate
aspartate
what enzyme is affected in orotic aciduria
ump synthase
mycophenolic acid works by inhibiting what enzyme
IMP dehydrogenase
explain the
1) intended function of methotrexate and
2) how it carries out that intended function
anti-neoplastic drug
inhibitor of DNA synthesis
binds DIHYDROFOLATE REDUCTASE (DHR) 100 times more tightly
DHR normally converts dietary folate to bioactive form THF in the liver. by blocking this action the THF supply is limited, limiting DNA replication in rapidly dividing cancer cells
explain sulfa drugs and
1) their intended function as well as
2) how they achieve that intended function
competitive inhibitors of the bacterial enzyme that incorporates PABA into folate
because humans acquire folate from their diet, the drug affects bacteria preferentially
describe the result of excess adenosine deaminase (ADA)
hemolytic anemia due to the insufficient levels of Adenine in RBCs
describe the result of insufficient adenosine deaminase (ADA) production
SCID (severe combined immunodeficiency)
due to the the inability of B and T cells to properly degrade Adenine, there is a build up. this build up negatively regulates (inhibits) Purine production and therefore inhibits DNA synthesis in the affected B and T cells. BUBBLE BOYS
describe the mechanism of action of Allopurinol
allopurinol inhibits xanthine oxidase
xanthine oxidase is involved in 2 consecutive steps in the creation of uric acid. by blocking xanthine oxidase we can treat gout
uric acid is normally soluble at a plasma concentration of how many mg/dL
7 mg/dL
gout occurs when plasma concentrations of uric acid exceeds what levels
9 mg/dL
which pyrimidines degrade into ketogenic products due to the action of uridine phosphorylase?
Uracil and cytosine (malonyl CoA)
which pyrimidines degrade into glucogenic products due to the action of uridine phosphorylase?
thymine (methylmalonyl CoA/succinyl CoA)
5-fluorouracil inhibits what enzyme
thmidylate synthase
jacked up APRT leads to what
renal lithiasis
HGPRT at > 8% normal HGPRT levels leads to what syndrome
Kelley Seegmiller syndrome
what is the primary enzyme of importance in pyrimidine nucleotide salvage
thmidine kinase
explain the role of cortisol in fasting states
cortisol is important in the catabolism of proteins. serves as a priming agent
without cortisol, death from hypoglycemia occurs
explain lactic acidosis
lactic acidosis occurs when the body is not producing energy from the TCA cycle. instead we are using pyruvate via the lactic acid cycle and ultimately we are producing too much lactic acid. usually occurs due to hypoxia but can also occur due to a dysfunctional pyruvate dehydrogenase
the only fuel that can cross the blood brain barrier is
glucose
explain glucokinase and how it functions as a glucose sensor
glucokinase genes regulated by insulin in liver
constitutive in pancreas
p. 121
type 1 diabetes results from
loss of pancreatic B cells
type 2 diabetes results from
insensitivity to insulin
RBCs can undergo hemolytic anemia due to inadequate expression of which glycolytic enzymes
explain the reason for the hemolysis
phosphoglucose isomerase, triosphosphate isomerase, pyruvate kinase,
no energy to supply Na+ pumps, leads to accumulation of water in cells and blowing up
the cofactor at the E1 site of pyruvate dehydrogenase is waht
B1 (TPP)
mutations in liver glycogen phosphorylase lead to what
GSD VI (hers)
mutations in muscle glycogen phosphorylase lead to what
GSD V (McArdle)
1) liver glycogen phosphorylase is inhibited by what?
2) what metabolite does not activate liver glycogen phosphorylase that does activate muscle glycogen phosphorylase
1) free glucose
2) AMP
a genetic disorder where the patient does not produce any glycogen synthase
GSD 0
a genetic disorder (autosomal recessive) where the patient has a deficiency in 4:6 transferase activity or production
usually exhibit hepatosplenomegally and death by 5 years of age
GSD IV (Andersen’s)
1) explain the role of calcium in glycogen breakdown
2) list drugs that affect this proces
1) muscle glycogen phosphorylase is very sensitive to activation by Ca++. calcium is released due to membrane depolarization as well as epinephrine action and inositol triphosphate signaling.
2) Dantrolene counteracts malignant hyperthermia induced by general anesthesia in genetically susceptible patients. in these patients reabsorption of Ca++ requires a ton of energy and leads to hyperthermia
palmitic acid, a 16 carbon, saturated fatty acid, when completely oxidized, can yield a maximum of how many ATP?
129 ATP
which amino acids are both ketogenic and glucogenic
PITTT or WIFTY if you prefer to use the one letter codes Phenylalanine Isoleucine Threonine Tyrosine Tryptophan
Acetyl CoA sits at the junction of anabolic and catabolic pathways. explain why high levels of Acetyl CoA generated from the breakdown of fatty acid synthesis cannot be utilized in the TCA cycle?
oxaloacetate is committed to gluconeogenesis
pyruvate dehydrogenase is active in what state? (phosphorylated or dephosphorylated?)
dephosphorylated
explain how calcium can upregulate PDH function/activation in cardiomyocytes
calcium binds to and activates PDP, which dephosphorylates PDH, activating it
explain how insulin may activate PDH in adipose tissue
PDP is a Mg dependent enzyme
in adipose tissue, insulin lowers Km of PDP for Mg, activating it at lower Mg conentrations. remember PDP activates pyruvate dehydrogenase
1) explain why pyruvate dehydrogenase deficiency leads to neonatal lactic acidosis.
2) how can we treat these kiddos
1) Without effective PDH, infants cannot properly convert pyruvate to acetyl CoA. Without Acetyl CoA, these little tykes must obtain energy strictly from conversion of pyruvate to lactate. what a bummer.
2) supplementation of vitamin B1, Lipoic acid and biotin
and/or a ketogenic diet
explain how arsenite affects the TCA cycle
where is arsenite found?
lipoic acid subunit (E2) of PDH is modified by arsenite. arsenite limits the availability of the lipoic enzyme by binding the S-H groups irreversibly. so PDH cannot function properly, neither can several TCA cycle enzymes, such as alpha ketoglutarate dehydrogenase
1) what is beriberi
2) list common symptoms
3) how do we diagnose
4) why do alcoholics tend to show a thymine deficiency?
5) beriberi in chronic alcoholics goes by a special name, what is that special name
6) why would patients with beriberi exhibit heightened levels of pyruvate and alpha-ketoglutarate?
1) nutritional deficiency condition in which the body does not have sufficient thiamine (B1)
2) weight loss, shortness of breath, difficulty walking, confusion, speech difficulties, involuntary eye movements. dry beri beri affects
3) measure blood thiamine levels
4) alcohol inhibits the absorption of thiamine
5) wernicke-korsakoff syndromeimpaired action of PDH and alpha-ketoglutarate dehydrogenase, which require TPP (B1 derivative) as an essential cofactor
how does citrate promote the storage of excess energy in the form of fat
citrate is an allosteric activator of acetyl CoA carboxylase
Acetyl CoA carboxylase converts Acetyl CoA to malonyl CoA (rate-limiting first step of fatty acid synthesis)
how does rat poison (fluoroacetate) inhibit the TCA cycle?
forms fluoroacetyl CoA, which subsequently binds with oxaloacetate to form fluorocitrate. fluorocitrate inhibits aconitase as well as PFK. therefore, fluorocitrate causes a build up of citrate, which inhibits glycolysis and PDH
how does Succinyl CoA relate to heme synthesis
succinyl CoA condenses with glycine and is decarboxylated to generate delata-ALA, the first step in heme biosynthesis
pyruvate carboxylase deficiency occurs in a higher prevalence in the Algonkian Indian tribes. what symptoms will these natives display if afflicted with this deficiency
buildup of pyruvate, more is converted to lactate than oxaloacetate
muscle weakness and uncontrolled muscle movements
what classic TCA cycle disorder manifests in infants via
metabolic acidosis
severe microcephaly
mental retardation
2-Oxoglutaric aciduria
what classic TCA disorder is characteried by sever neurological impairment and causes death within two years of life. patients present with
encephalomyopathy
dystonia
increased urinary excretion of fumarate, succinate, alpha-ketoglutarate and citrate
fumarase deficiency
what recently discovered TCA cycle disorder is associated with mutation in SUCLA2 and SUCLG1
succinyl-CoA synthetase
what TCA cycle disorder is associated with profound hypotonia, progressive dystonia, muscular atrophy, severe sensory neural hearing impairment
mitochondrial depletion syndrome
1) what are ferredoxins?
2) what are some common ferredoxins and what are their functions?
1) small proteins that serve as carriers of electrons in mitochondrial cytochrome P-450 systems. contain sulfur and iron, allow exchange of electrons between ferredoxins.
2) adrenodoxin (FDX1) - biosynthesis of steroids/metabolism of vitamin D and bile acids
(FDX2) - biosynthesis of heme-a
1) explain the role of ubiquinone radical in OxPhos
1) ubiquinone radical is an intermediate in teh transffer of electrons from complex I to ubiquinone as well as the transfer from reduced ubiquinone to complex III
1) how does cytochrome C relate to apoptosis
1) cytochrome C normally functions as a mobile carrier of electrons between complexes III and IV of mitochondrial electron transport chain. apoptosis can be initiated by causing cytochrome C to be released from the mitochondrial membrane, initiating a cascade of biochemical events and the murder of the cell via Caspases
explain what rotenone is and how it affects humans
NADH dehydrogenase inhibitor (complex I)
inhibits the transfer of electrons from complex I to ubiquinone
can be overcome by administration of menadione
chronic poisoning related to Parkinson’s disease somehow
explain how cyanide affects the electron transport chain
blocks component of complex IV, preventing 02 reduction (TERMINAL STEP). If caught early, nitrites can prevent death by competing with cyanide for binding with complex IV
cyanide works by what type of inhibition of complex IV
noncompetitive inhibitor
carbon monoxide works by what type of inhibition of complex IV
competitive inhibitor (raises Km)
