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Glycolysis and Pyruvate Dehydrogenase (Biochem) Flashcards

1
Q

in which cells does glycolysis occur?

A
  • glycolysis occurs in all cells

- in RBC, glycolysis represents the ONLY energy-yielding pathway available (bc they don’t have mito)

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2
Q

normal blood glucose in mM?

A
  • normal = 4-6 mM

- 70-110 (or 60-100) mg/dL

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3
Q

Why do we give Potassium Chloride to a patient in DKA?

A
  • because we’re also giving insulin, and insulin causes K to be absorbed by the cells.
  • Insulin causes Potassium to shift into the cells thereby decreasing the extracellular K level.
  • That’s why insulin is used in the treatment of hyperkalemia.
  • Level of Potassium in the serum also affects insulin secretion from the pancreas.
  • Because the beta cells have an ATP dependent K channel which, when closed, leads to retained K inside the beta cell which favors depolarization thereby enhancing Calcium mediated release of secretory granules.
  • Therefore, in hyperkalemia more K will enter the beta cell and insulin secretion will increase
  • and conversely in hypokalemia the K ions are more likely to leave the beta cell and so insulin secretion will decrease.
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4
Q

the first steps in glucose metabolism in any cell are:

A
  • transport across the membrane

- and phosphorylation by kinase enzymes inside the cell to prevent it from leaving via the transporter

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5
Q

most of the carbs in food are in complex forms like:

A
  • starch: amylose and amypectin
  • disaccharides: sucrose and lactose
  • only a very small amount of the total carbs ingested are monosaccharides
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6
Q

What begins to digest carbs in the mouth?

A
  • in the mouth, secreted salivary amylase randomly hydrolyzes the starch polymers to dextrin ( less than 8-10 glucoses)
  • upon entry into the stomach, the acid pH destroys the salivary amylase
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7
Q

What breaks down dextrin? and where does this occur?

A
  • in the intestine, dextrin are hydrolyzed to the disaccharides maltose and isolates
  • disaccharides in the intestinal brush border complete the digestion process
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8
Q

Maltase function

A

Maltase cleaves maltose to 2 glucoses

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9
Q

isomaltase function

A

isomaltase cleaves isomaltase to 2 glucoses

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10
Q

lactase function

A

lactase cleaves lactose to glucose and galactose

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11
Q

sucrase function

A

sucrase cleaves sucrose to glucose and fructose

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12
Q
  • how does glucose get into the mucosal cells?

- is this active or passive transport?

A
  • the sodium/glucose transporter moves glucose into mucosal cells
  • this is an Active Transporter
  • glucose entry into most cells is concentration driven
  • it is INDEPENDENT OF SODIUM!!!!!!!
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13
Q

What is the normal concentration of glucose in peripheral blood?

A

4-6 mM or 70-110 mg/dL

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14
Q

Where is the GLUT 1 transporter found?

- kinetics

A
  • GLUT 1 and GLUT 3 mediate basal glucose uptake in most tissues, including brain, nerves and RBC
  • Their high affinities for glucose ensure glucose entry even during periods of relative hypoglycemia
  • at a normal glucose concentration, GLUT1 and GLUT 3 are at Vmax.
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15
Q
  • GLUT 2 is found where?

- kinetics?

A
  • GLUT 2 is a low-affinity transporter, found in hepatocytes
  • after a meal, portal blood = rich in glucose
  • GLUT 2 captures the excess glucose primarily for storage
  • when the glucose concentration drops below the Km for the transporter, much of the remainder leaves the liver and enters the peripheral circulation
  • in the beta islet cells of the pancreas, GLUT 2 (along with glucokinase) serves as the glucose sensor for insulin release
  • Bc both GLUT 2 and glucokinase have high Km values for glucose, glucose is transported and phosphorylated via 1st order kinetics (directly proportional to glucose concentration in the bloodstream)
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16
Q

GLUT 4 translocation to the cell membrane in skeletal muscle is stimulated by??

A
  • exercise

- this effect, which is INDEPENDENT OF INSULIN, involves a 5’ AMP-activated kinase

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17
Q

Where is the GLUT 3 transporter found?

A
  • GLUT 1 and GLUT 3 mediate basal glucose uptake in most tissues, including brain, nerves and RBC
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18
Q
  • Where is GLUT 4 found?

- How does it respond?

A
  • GLUT 4 is in adipose tissue and muscle
  • it responds to the glucose concentration in peripheral blood
  • the rate of glucose transport in these 2 tissues is increased by insulin, which stimulates the movement of additional GLUT 4 transporters to the membrane
  • decreased insulin decreases the # of plasma membrane GLUT 4 transporters by endocytosis of the transporter into cytoplasmic vesicles.
  • increased insulin increases the # of plasma membrane GLUT 4 transporters through fusion of the cytoplasmic vesicles containing the membrane-bound GLUT 4 with the plasma membrane.
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19
Q

What signals insulin release in the beta islet cells of the pancreas?

A
  • the GLUT 2 transporter and glucokinase serves as the glucose sensor for insulin release from the beta islet cells of the pancreas
  • insulin secretion by the pancreatic beta cells is biphasic
  • glucose stimulates the first phase (within 15 mins) with release of preformed insulin
  • the 2nd phase (several hours) involves insulin synthesis at the gene level
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20
Q

GLUT 1:

  • tissues
  • Km, Glucose
  • functions
A
  • most tissues (ESP BRAIN and RBC)
  • Km, glucose: approx 1 mM
  • f(x): basal uptake of glucose
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21
Q

GLUT 2:

  • tissues
  • Km, Glucose
  • functions
A
  • liver, pancreatic beta cells
  • Km, glucose: approx 15 mM
  • f(x): uptake and release of glucose by the liver beta cell glucose sensor
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22
Q

GLUT 3:

  • tissues
  • Km, Glucose
  • functions
A
  • most tissues
  • Km, glucose: approx 1 mM
  • f(x): basal uptake
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23
Q

GLUT 4:

  • tissues
  • Km, Glucose
  • functions
A
  • skeletal muscle, adipose tissue
  • Km, glucose: approx 5 mM
  • f(x): insulin-stimulated glucose uptake; stimulated by exercise in skeletal muscle
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24
Q

Although basal transport occurs in all cells indepdently of insulin, the transport rate ____ in adipose tissue and muscle when insulin levels ____

A

Although basal transport occurs in all cells indepdently of insulin, the transport rate INCREASES in adipose tissue and muscle when insulin levels RISE

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25
Q

Why does the transport rate of glucose into muscle cells INCREASE when insulin levels increase?

A
  • the transport rate of glucose into muscles increases when insulin levels increase bc:
  • muscle stores excess glucose as glycogen
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26
Q

Why does the transport rate of glucose into adipose tissue INCREASE when insulin levels increase?

A
  • the transport rate of glucose into adipose tissue INCREASES when insulin levels increase bc:
  • adipose tissue requires glucose to form dihydroxyacetone phosphate (DHAP) which is converted to glycerol phosphate and is used to store incoming FA as TG
  • TGL = 3 FA attached to glycerol.
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27
Q

insulin ____ PFK-2 in the liver by _____

A

insulin stimulates PFK-2 in the liver by dephospho rylation

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28
Q

What 3 enzymes in Glycolysis are rate-controlled and catalyze irreversible steps?

*Because of these 3 enzymes, Glycolysis is Irreversible, when the liver produces glucose, different reactions and therefore different enzymes must be used at these points!

A
  1. Hexokinase (all tissues) aka Glucokinase (in liver)
    - Glucose –> Glucose 6P
    - Mg2+ cofactor; requires ATP –> ADP
    - Glucose 6P downregulates
    - insulin stimulates
  2. PFK-1
    - Fructose 6P –> Fructose-1,6 bis P
    - ATP –> ADP
    - AMP stimulates
    - ATP, citrate inhibit/downregulate
  3. Pyruvate Kinase
    - Phosphoenolpyruvate (PEP) –> Pyruvate
    - ADP –> ATP
    - Fructose 1, 6 bis P is an allosteric activator of forward reaction (of pyruvate kinase)
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29
Q

Pyruvate Kinase Deficiency

- Findings

A
  • 2nd MC genetic deficiency that causes hemolytic anemia
  • AR
  • (#1 MCC = G6PD deficiency)
  • Causes:
  • chronic hemolysis –> hemolytic anemia
  • increased BPG –> lower-than-normal O2 affinity of HbA
  • no heinz bodies (heinz bodies are more characteristic of G6PD deficiency)
  • results from a partial enzyme defect
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30
Q

Effects of 2,3 bisphosphoglycerate on the O2/Hb curve

A
  • RBC have bisphosphoglycerate mutase which converts 1,3 BPG to 2,3 BPG.
  • 2,3 BPG binds to the beta chains of HbA and decreases its affinity for oxygen
  • (shifts Hb/O2 curve to the R. Normal R shifts allow for O2 to be unloaded in tissues)
  • an abnormal increase in RBC 2,3-BPG might shift the curve far enough to the R that HbA is not fully saturated in the lungs
  • 2,3-BPG doesn’t bind well to HbF because HbF doesn’t have a beta subunit.
  • Summary:
  • 2,3-BPG decreases O2 affinity for Hb
  • 2,3-BPG increases O2 unloading
  • 2,3-BPG regulates how RBC carries O2
  • HbF has a higher affinity for O2 than maternal HbA
  • this allows transplacental passage of O2 from mother to fetus
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31
Q

NAD(H) is made from

A

niacin (Vitamin B3)

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32
Q

Hexokinase/Glucokinase

A
  • glucose entering the cells is trapped by phosphorylation using ATP
  • Hexokinase is widely distributed in tissues
  • glucokinase is only found in hepatocytes and pancreatic beta islet cells
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33
Q

Hexokinase

  • where is it found
  • Km
  • inhibited by?
A
  • found in most tissues
  • low Km (0.05 mM in erythrocytes)
  • inhibited by glucose 6P
34
Q

What does Arsenate do?

A
  • Arsenate inhibits conversion of glyceraldehyde 3P to 1,3 bisphosphoglycerate by mimicking phosphate in the reaction.
  • this is the reaction catalyzed by Glyceraldehyde 3P dehydrogenase
  • The arsenate-containing product is water labile, enabling glycolysis to proceed, but resulting in no ATP production
35
Q

Glucokinase

  • where is it found
  • Km
  • Induced by?
A
  • found in hepatocytes and pancreatic beta islet cells
  • (along with GLUT2 acts as the glucose sensor)
  • High Km (10 mM)
  • induced by insulin in hepatocytes
36
Q

Phosphofructokinase-1 (PFK-1)

A
  • PFK-1 is the rate-limiting enzyme and main control point of glycolysis
  • catalyzes Fructose 6P –> fructose 1, 6 bisP
  • requires ATP
  • PFK-1 is inhibited by ATP and citrate
  • PFK-1 is activated by AMP
  • F2,6 BP activates PFK-1
  • insulin stimulates and glucagon inhibits PFK-1 in hepatocytes by an indirect mechanism involving PFK-2 and fructose 2,6 bisP
  • in liver, PFK-1 is stimulated by Fructose 2,6 bisP, so the liver can make FA
37
Q

Phosphofructokinase-2 (PFK-2)

A
  • Fructose 6P –> Fructose 2,6 bisP
  • only in liver
  • insulin activates PFK-2 via the tyrosine kinase receptor and activation of protein phosphatases
  • F2,6 BP activates PFK-1
  • Glucagon inhibits PFK-2 via cAMP dependent protein kinase
  • low levels of F2,6 BP inhibits PFK-1
38
Q

RBC pathways

A
  • Glycolysis (can only use glucose as fuel)
  • hexose monophosphate shunt: antioxidant NADPH
  • cation transport
  • MetHb –> Hb (needs NADH)*
  • in RBCs, 1/2 to 1% of Hb is Fe3+ and NADH reduces Fe3+ to Fe2+
39
Q

What causes coagulation necrosis in an MI?

A
  • during ischemic episodes the lack of O2 forces cells to rely on anaerobic glycolysis
  • this increases production of lactic acid
  • the increased intracellular acidosis can cause proteins to denature and precipitate, leading to coagulative necrosis
40
Q

Glycolysis (summary)

A
  • cytoplasmic process
  • converts 1 Glucose into 2 Pyruvates
  • releases energy captured in 2 substrate-level phosphorylations and one oxidation reaction
41
Q

Glyceraldehyde 3P Dehydrogenase

A
  • catalyzes an oxidation and addition of inorganic phosphate to its substrate
  • results in the production of a high-energy intermediate 1,3 bisphosphoglycerate (1,3 BP glycerate)
  • reduces NAD to NADH
  • if oxidation is aerobic, the NADH can be deoxidized (indirectly) by the mitochondrial ETC , thus providing energy for ATP synthesis by oxidative phosphorylation
42
Q

3-Phosphoglycerate Kinase

A
  • transfers the high-energy phosphate bond from 1,3 BP glycerate to ADP = SUBSTRATE-LEVEL Phosphorylation
  • reaction: 1,3 BP glycerate + ADP –> 3P glycerate + ATP
  • substrate-level phosphorylations are NOT dependent on O2 and are the only means of ATP generation in anaerobic tissue
43
Q

Pyruvate Kinase

A
  • last enzyme in aerobic glycolysis
  • catalyzes a substrate-level phosphorylation reaction by transferring a phosphate from PEP to ADP.
  • Reaction: PEP + ADP to Pyruvate + ATP
  • activated by fructose 1,6 BP from the PFK-1 reaction (feed-forward activation)
44
Q

Lactate Dehydrogenase

A
  • only used in anaerobic glycolysis
  • reoxidizes NADH to NAD, replenishing the oxidized coenzyme for glyceraldehyde 3P dehydrogenase
  • w/o mitochondria and O2, glycolysis would stop when all the NAD had been reduced to NADH.
  • by reducing pyruvate to Lactate and oxidizing NADH to NAD, LDH prevents this from happening.
  • in aerobic tissues, lactate does not normally form in significant amounts
  • the resulting acidosis generated by anaerobic glycolysis can cause proteins to denature and precipitate, leading to coagulation necrosis
45
Q

Important intermediates of glycolysis

A
  1. DHAP (dihydroxyacetone phosphate) is used in liver and adipose tissue for TG synthesis
    - DHAP –> Glycerol 3P (which is used for TGL synthesis and electron shuttle)
  2. 1,3 BPG and PEP are high-energy intermediates used to generate ATP by substrate-level phosphorylation
46
Q

Steps where Substrate-level phosphorylation occurs in Glycolysis

A
  1. phosphoglycerate kinase converts 1,3 BP glycerate + ADP to 3P glycerate + ATP
  2. Pyruvate Kinase converts PEP + ADP to Pyruvate + ATP
    - substrate-level phosphorylations are NOT dependent on O2 and are the only means of ATP generation in anaerobic tissue
47
Q

Anaerobic glycolysis yields

A

2 ATP/glucose by substrate-level phosphorylation

48
Q

Aerobic glycolysis yields

A

2 ATP/glycose + 2 NADH/glucose that can be utilized for ATP production in the mitochondria (oxidative phosphorylation)

  • however: the inner mitochondrial membrane is impermeable to NADH.
  • so, cytoplasmic NADH is deoxidized to NADH and delivers its electrons to one of 2 electron shuttles in the inner membrane:
    1. Malate Shuttle: the electrons are passed to mitochondrial NADH and then to the ETC
    2. Glycerol Phosphate Shuttle: electrons are passed to mitochondrial FADH2
49
Q

Malate Shuttle

A
  • the inner mitochondrial membrane is impermeable to NADH.
  • so, cytoplasmic NADH is deoxidized to NADH and delivers its electrons to one of 2 electron shuttles in the inner membrane.
  • the malate shuttle produces:
  • a Mitochondrial NADH and
  • and yields approx 3 ATP by oxidative phosphorylation
50
Q

Glycerol Phosphate Shuttle

A
  • the inner mitochondrial membrane is impermeable to NADH.
  • so, cytoplasmic NADH is deoxidized to NADH and delivers its electrons to one of 2 electron shuttles in the inner membrane.
  • the GP Shuttle produces:
  • a mitochondrial FADH2
  • and yields approx 2 ATP by oxidative phosphorylation
51
Q

Pathway for ATP production in RBC

A

RBC don’t have mitochondria, so anaerobic glycolysis is the only pathway for ATP generation.
- yields 2 ATP/glucose

52
Q

Adaption to high altitudes (low PO2) involves

A
  • increased respiration
  • respiratory alkalosis
  • lower P50 for hemoglobin (initial)
  • increased rate of glycolysis
  • increased [2,3-BPG] in RBC (12-24 hrs)
  • Normal P50 for Hb restored by the increased level of 2,3-BPG
  • increased Hb and hematocrit (days-weeks)
  • Respiration reaction: CO2 + H2O –> H2CO3 –> H+ + HCO3-
  • if you decrease the CO2 you’ll decrease the amount of H+ produced
  • therefore, at higher altitudes, and increased respiration –> you have an increased pH
  • 2,3-BPG doesn’t mind to HbF because HbF doesn’t have a beta subunit.
53
Q

Pyruvate Kinase Deficiency

- pathophysiology

A
  • RBC has no mitochondria and is totally dependent on anaerobic glycolysis for ATP
  • in PKD, the decrease in ATP causes the RBC to lose its characteristic biconcave shape
  • this signals destruction of RBC in spleen
  • Also, decreased ion pumping by Na+/K+ ATPase results in loss of ion balance
  • -> osmotic fragility –> swelling and lysis
54
Q

Lactase Deficiency (after ingestion of lactose)

  • Sx
  • WHY does this occur?
  • Dx
  • Tx
A
  • Sx: diarrhea, bloating, cramps
  • bacteria have no O2, so they get rid of electrons by producing CH4 and sulfur compounds and small organic acids
  • the acids are osmotically active and result in the movement of water into the intestinal lumen
  • Dx: positive H-breath test after an oral lactose load
  • Tx: dietary restriction of milk/milk products (except unpasteurized yogurt, which contains active lactobacillus) or by lactase pills
55
Q

What is the mechanism by which Galactose causes cataracts?

A
  • Reaction:
    1. Lactose –> glucose + galactose
    2. if galactose accumulates, it moves out of the blood and deposits in the lens of the eye
    3. There it is converted to galactitol by Aldose reductase.
  • when making galactitol, all C have an OH group. so it gets trapped in the lens and can’t leave
  • if galactitol is trapped in the lens it causes swelling and cataracts (osmotic damage)
  • Cataracts: opacification of lens affection vision.
  • painless, often bilateral
56
Q

Galactokinase Deficiency

A
  1. Galactokinase deficiency
    - galactokinase converts galactose to galactose 1P
    - requires 1 ATP
    - less severe than Galactose 1 -P uridyltransferase deficiency
57
Q

Galactose 1 -P uridyltransferase deficiency

  • What reaction should this enzyme catalyze
  • Sx and Tx
A
  • Converts Galactose 1P to Glucose 1P
  • more severe than Galactokinase deficiency bc you not only develop galactosemia, but Galactose 1-P also accumulates in the liver, brain and other tissues
  • cataracts early in life
  • vomiting, diarrhea following lactose ingestion
  • failure to thrive
  • Swelling in the brain: hypotonia, lethargy, mental retardation
  • liver damage (acute liver injury can cause vomiting)
  • hyperbilirubinemia (bc liver = site of bilirubin conjugation)
  • bleeding problems (results from liver damage)
  • Tx: avoid galactose, including breast milk. Give lactose-free formula supplemented with sucrose
58
Q

Cataracts

  1. Def
  2. Risk Factors
A
  1. Cataracts: opacification of lens affection vision.
    - painless, often bilateral
  2. Risk Factors: age, smoking, excessive ethanol use, prolonged corticosteroid use, excessive sunlight, classic galactosemia, galactokinase deficiency, trauma, diabetes (sorbitol), infection (rubella)
59
Q

What is the mechanism by which diabetics get cataracts?

A
  1. Aldose reductase converts Glucose to Sorbitol

2. Sorbitol accumulates and causes osmotic damage = cataracts

60
Q

Galactosemia

A
  • AR
  • results from a defective gene encoding either galactokinase or galactose 1-P uridyltransferase
  • can be caused by over 100 heritable mutations
  • 1/60,000 births
  • Elevated blood and urine [galactose]
  • can result in decreased glucose synthesis and hypoglycemia
  • Sx begin around day 3 in a newborn and include hallmark cataracts.
  • Jaundice and hyperbilirubinemia do not resolve if the infant is treated with phototherapy
  • in the galactosemic infant, the liver (site of bilirubin conjunction) develops cirrhosis
  • Severe bacterial infections are common (i.e. E. coli sepsis) in untreated infants
  • failure to thrive, hypotonia, lethargy and mental retardation are other common features
  • Ex) 2wk old infant who was being breast-fed returned to hospital bc frequently vomited, had persistent fever, and looked yellow since birth.
  • has early hepatomegaly and cataracts
61
Q

1 day old female delivered at 34 weeks due to intrauterine growth retardation developed progressive respiratory failure that required intermittent mechanical ventilation.

  • her blood glucose was 13.4 mM and increased to 24.6 mM.
  • insulin administered to normalize her glucose
  • no C-peptide was detectable
  • her parents were 2nd cousins
  • both had symptoms of mild diabetes controlled by diet alone
  • genetic studies showed missions mutation (Ala378Val) in the glucokinase gene
  • the parents were heterozygous and the infant was homozygous for the mutation
A
  • This infant has Glucokinase deficiency
  • remember: Glucokinase phosphorylates Glucose, trapping it the liver. It is necessary for glycolysis to occur
  • near-complete deficiency of glucokinase activity is assoc with permanent neonatal T1 diabetes
  • Some mutations in the glucokinase gene alter the Km for glucose (although not in this patient)
  • those mutations that DECREASE Km (increasing its affinity for glucose) result in hyperinsulinemia and hypoglycemia
  • Conversely, mutations that INCREASE the Km (decreasing its affinity for glucose) are associated with some cases of maturity-onset diabetes of the young (MODY)
62
Q

Why does a high fructose drink supply a quick source of energy in both aerobic and anaerobic cells?

A

Because dihydroxyacetone phosphate and glyceraldehyde (the products of fructose metabolism) are DOWNstream from the key-regulatory and rate-limiting enzyme of glycolysis (PFK-1)

63
Q

Fanconi Syndrome

A
  • renal proximal tubule defect (Fanconi): where glucose, amino acids, uric acid, phosphate and bicarbonate are passed into the urine, instead of being reabsorbed.
  • can be inherited or caused by drugs or heavy metals
64
Q

TPP (Thiamine pyrophosphate) is made from

A

Thiamine (Vitamin B1)

65
Q

Coenzyme A (CoA) is made from

A

pantothenate (Vitamin B5)

66
Q

if you decrease the Km of an enzyme for a specific substrate you ____

A
  • increase the affinity of that enzyme for that substrate
  • ex) mutations that DECREASE the Km of glucokinase (increasing its affinity for glucose) result in hyperinsulinemia and hypoglycemia
  • remember: Glucokinase phosphorylates Glucose, trapping it the liver
67
Q

Hereditary Fructose Intolerence

A
  • AR
  • 1/20000
  • due to defect in the gene that encodes aldolase B in fructose metabolism
  • in the absence of the enzyme, fructose 1P accumulates in hepatocytes and in proximal renal tubules
  • this traps inorganic phosphate in this substance, removing it from the phosphate pool
  • the drop in phosphate levels prevents its use in other pathways, such as glycogen breakdown and gluconeogenesis
  • eventually the liver (and kidney) becomes damaged due to accumulation of trapped fructose 1P
  • ex) 4mo infant was breast-fed and developing normally. but when he was weaned mother began feeding him fruit juices. Within a few weeks the child became lethargic, yellow-skinned, and vomited frequently, and had frequent diarrhea.
  • will find sugar in urine on testing, but the sugar won’t react with glucose dipsticks
  • Tx: exclude fructose and sucrose from diet. But complete exclusion of these sugars is difficult, and failure to correct the diet and prolonged fructose ingestion could eventually lead to a proximal renal disorder resembling Fanconi syndrome.
68
Q

FAD(H2) is made from

A

riboflavin (Vitamin B2)

69
Q

if you increase the Km of an enzyme for a specific substrate you ____

A
  • DECREASE the affinity of that enzyme for that substrate
  • ex) mutations that INCREASE the Km of glucokinase (decreasing its affinity for glucose) are associated with some cases of maturity-onset diabetes of the young (MODY)
70
Q

Aldolase B (Fructose 1-Phosphate aldolase activity) deficiency

A
  • Fructose 1-P accumulates in tissues and causes damage
  • lethargy, vomiting
  • liver damage (acute liver injury can cause vomiting)
  • hyperbilirubinemia (bc liver = site of bilirubin conjugation)
  • hyperuricemia (bc kidneys aren’t working properly)
  • renal proximal tubule defect (Fanconi): where glucose, amino acids, uric acid, phosphate and bicarbonate are passed into the urine, instead of being reabsorbed.
  • aka hereditary fructose intolerence: occurs after learning from breast milk, i.e. 1yo previously healthy kid)
  • sx are reversed after removing fructose and sucrose from diet
71
Q

Cofactors and Coenzymes used by pyruvate dehydrogenase include

A
  • Thiamine pyrophosphate (TPP) from the vitamin thiamine (Vitamin B1)
  • lipoic acid
  • coenzyme A (CoA) from pantothenate (vitamin B5)
  • FAD(H2) from riboflavin (Vitamin B2)
  • NAD(H) from niacin (Vitamin B3) (some may be synthesized from tryptophan)
  • Pyruvate Dehydrogenase: Pyruvate –> Acetyl CoA
  • Acetyl CoA inhibits pyruvate dehydrogenase
  • Pyruvate Dehydrogenase is found in MITOCHONDRIA
72
Q

Why does lactose deficiency increase as we age?

A
  • bc as we age euchromatin is converted to heterochromatin
  • Lactose deficiency = #1 gene disorder of all time
  • 90% asians, 50% mexicans, also high in blacks
73
Q

Why can high levels of galactose lead to cataracts but high levels of fructose don’t?

A
  • If you have high blood [fructose], no problem. You can just pee it out.
  • Fructokinase deficiency is benign!
  • Aldose reductase is an enzyme that usually reduces aldehyde group of aldoses
  • Fructose is not an aldose sugar (has no aldehyde), so it’s not a substrate for aldose reductase in the lens
  • Fructokinase deficiency is benign!
74
Q

Glycolysis occurs in the

A

Cytoplasm

75
Q
  • Alcoholics are deficient in ____

- Sx of this deficiency

A
  • Thiamine
  • Ethanol inhibits absorption
  • Sx: ataxia, nystagmus, opthalmoplegia, nystagmus, memory loss and confabulation, cerebral hemorrhage
  • Wernicke-Korsakoff syndrome
  • insufficient Thiamine (VB1) significantly impairs glucose oxidation, causing highly aerobic tissues (i.e. brain, cardiac muscle) to fail first.
  • additionally, branched chain AA are sources of energy in brain and muscle
  • CHF may be a complication (wet beri beri) owing to inadequate ATP and accumulation of ketoacids in the cardiac muscle
76
Q

What happens if you give glucose without thiamine?

A
  • lactic acidosis
  • glucose load will increase glycolysis but if you lack thiamine, phosphate dehydrogenase will not work,
  • and cells will make lactate to regenerate NAD
  • Remember: Thiamine = Vitamin B1
77
Q

Pathophysiology of Wet Beri Beri

A
  • CHF may be a complication (wet beri beri) owing to inadequate ATP and accumulation of ketoacids in the cardiac muscle
  • insufficient Thiamine (VB1) significantly impairs glucose oxidation, causing highly aerobic tissues (i.e. brain, cardiac muscle) to fail first.
  • additionally, branched chain AA are sources of energy in brain and muscle
78
Q

2 other enzyme complexes similar to pyruvate dehydrogenase that use thiamine are

A
  • alpha-ketoglutarate dehydrogenase (TCA)
  • Branched-chain ketoacid dehydrogenase (metabolism of branched-chain AA)
  • additionally, branched chain AA are sources of energy in brain and muscle
  • Remember: Thiamine = Vitamin B1
79
Q

GLUT 2

  • Km
  • location and function
A
  • High Km
  • High Km allows it to have first order kinetics; absorption directly proportional to [glucose] in bloodstream
  • liver (storage)
  • beta islets (glucose sensor)
80
Q

GLUT 4

  • Km
  • location and function
A
  • Lower Km
  • insulin stimulated
  • adipose and muscle
81
Q

regulation of pyruvate dehydrogenase (PDH)

A
  1. PDH is active when dephosphorylated by PDH phosphatase
    - PDH phosphatase is activated by calcium (exercise increases intracellular Ca2+ –> activates PDH by activating PDH phosphatase)
  2. PDH is INACTIVE when PHOSPHORYLATED by PDH kinase
    - PDH kinase is inhibited by substrate (pyruvate and ADP i.e. during exercise, energy use)
    - PDH kinase is activated by products (Acetyl CoA, NADH, CO2)
    - an increased NADH/NAD+ ratio (seen when cell’s need for reduced NADH is being met) –> decreases PDH activity by activating PDH kinase

naplan (20 decks)

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