Metabolism Flashcards
Oxidation
Loss of electrons from an atom. occurs during the addition of an O2 molecule or when H+ is removed
Reduction
addition of electrons to an atom. occurs during the addition of hydrogen or the removal of oxygen
Where does the conversion of pyruvate to acetyl coa take place?
Matrix of the mitochondria
What are the 4 fates of Acetyl CoA
1) primary fate is the CAC. Produces ATP, H2O, CO2.
2) Lipogenesis. formation of fatty acids which go through esterification to form triacylglycerol
3) Ketogenesis- formation of ketone bodies
4) cholesterologenesis- formation of cholesterol and then steroids. involves the transfer of acetyl units in the cytosol. So Acetylo CoA is the precursor of steroids
Fuel preferences of liver
fatty acids
glucose
amino acids
Fuel preferences of skeletal muscle
At rest: fatty acids
exertion: glucose
Fuel preference for the brain
Fed state: glucose
Starvation: ketone bodies/glucose
Fuel preferences for adipose tissue
fatty acids
fuel preferences for heart muscle
prefers fatty acids, but it can use anything
Amylopectin
found in potatoes, rice, corn, bread
enzyme: isomaltase
amylose
potatoes, rice, corn, bread
enzyme: maltase
Starch
mixture of amylose and amylopectin
polymer composed entirely of glucose
potatoes, rice, corn, bread
enzyme: maltase and isomaltase and amylase
Sucrose
table sugar, desserts
enzyme: sucrase
Lactose
milk, milk products
enzyme: lactase
Fructose
Fruit, honey
Glucose
Fruit, honey, grapes
Maltose
Barley
Enzyme: maltase
Trehalose
Young mushroom
enzyme: trahalase
Cellulose
fiber in plants. not digestable by humans
Calories of Carbs
% Caloric Store: 1
% body weight: .6
kcal/g dry: 4
kcal/g wet: 1-1.5
calories of protein
% Caloric Store: 23
% body weight: 14
kcal/g dry: 4
kcal/g wet: 1-1.5
Calories of fat
% Caloric Store: 76
% body weight: 20
kcal/g dry: 9
kcal/g wet: 9
% body weight of H2O and minerals
65%
how much glucose does brain use every day
120g
how much glucose does muscle tissue use every day
40g
what level must blood glucose be maintained above to avoid hypoglycemia
60mg/100mL
affinose
carb found in leguminous seeds
Phase I of Starvation
Blood glucose is supplied exogenously.
All tissues are using glucose
Brain is also using glucose
Phase II of Starvation
Blood glucose originates from glycogen and hepatic gluconeogenesis.
All tissues except the liver are using glucose, muscle and adipose tissue are using them at diminished rated.
Brain is using glucose
Phase III of Starvation
Blood glucose oriniated from hepatic gluconeogensis and glycogen
All tissues except the liver are using glucose. Muscle and adipose tissue glucose use is between phase II and IV
Brain is using glucose
Phase IV of Starvation
blood glucose from hepatic and renal gluconeogenesis.
Only brain, RBCs, renal medulla, and small maounts of muscle still using glucose
Brain is using glucose and ketone bodies
Phase V of starvation
Blood glucose is from hepatic and renal gluconeogenesis
Renal medulla and RBCs using glucose. Brain using glucose at a diminished rate.
Brain using glucose and ketone bodies
Insulin
peptide hormone secreted by beta cells of the pancreas
regulates glucose metabolism. maintains low blood glucose levels. Counters he function of hyperglycemia generating hormones.
promotes glycolysis on a long term basis, as well as glycogen synthesis
glycogenolysis
the breakdown of glycogen to glucose-1-phosphate and glucose in the liver and muscles by the enzyme glycogen phosphorylase
activated by hypoglycemia and increased glucagon
Glycolysis
single glucose molecule converts into:
2 pyruvic acid
2 ATP
2 NADH
2 H2O
activated by hyperglycemia and increased insulin
gluconeogenesis
generation of glucose from non-carb carbon substrates such as pyruvate, lactate, glycerol, and glucogenic amino acids amino acids
stimulated by hypoglycemia and increased glucagon
glucogenesis
formation of glycogen from glucose.
stimulated by hyperglycemia and increased insulin
Carb metabolism in RBCs
lack mitochondria, cannot metabolize fatty acids or amino acids. Entirely dependent on glycolysis
Carb metabolism in the brain
has an absolute requirement for glucose.
120 grams daily. very smally reserve of glycogen in brain tissue
Carb metabolism in muscle and heart cells
major glycogen stores. cannot mobilize glycogen or glucose in to the blood.
carb metabolism in Adipose tissue
convert excess glucose to fat
SGLT1
sodium glucose transporter 1. Hexose transporter against concentration gradient. Co-transports one molecule of glucose or galactose along with 2 Na ions. Does not tranport fructose
expressed in intestinal mucosa and kidney tubules
GLUT 2
Hexose transporter with concentration gradient.
Insulin independent and low affinity for glucose, high capacity transport in liver. allows GLUT2 to change transport rate in proportion to increasing glucose concentrations.
found in liver, intestine, and kidneys. bidirectional transport.
serves as a glucose sensor to pancreatic beta cells. transports glucose out of the intestines into the blood stream, and into the liver.
GLUT 4
Hexose transporters down the concentration gradient
high affinity for glucose
gets glucose after we have eaten it. not active during the fasting state.
functions at max rate when glucose conc is 5mM
skeletal muscle, heart, adipocytes
Which transporters have a high affinit for glucose
GLUT 1,3,4
Which transporters are fructose transporters
Class II: 5,7,9,11
Which transporters are glucose transporters
GLUT 1-4
Three key enzymes that regulate glycolysis
1) Hexokinase/Glucokinase- priming stage ATP investment
2) PFK-1/phosphofructo kinase-1 -Splitting stage
3) Pyruvate kinase -oxidoreduction phosphorylation stage (these steps occur twice for every glucose molecule)
Deficiencies in which enzymes cause hemolytic anemia
hexokinase
glucose phosphate isomerase
aldolase
triosephosphate isomerase
phsophoglycerate isomerase
enolase
pyruvate kinase
Comapre Hexokinase to Glucokinase
Hexokinase: present in all cell types, allosterically inhibited by G6P, constituitive enzyme (present at all times whether activated or not), low Km for glucose (saturated at low glucose concentrations), can’t handle high levels of glucose
Glucokinase: Present in liver and pancreas, inactive in nucleus and active in cytosol, inhibited by F6P, enzyme activity induced by insulin because it increases expression of the gene, high Km for glucose, not saturated at normal physiological glucose concentration, can handle large concentration of glucose in the liver.
What are the allosteric regulators of PFK-1
positive: F2,6BP, AMP, ADP
Negative: More ATP, More citrate
What are the regulators of glucokinase
activators promote translocation from nucleus to the cytosol: high levels of glucose. insulin
inhibitors promote translocation to the nucleus: fructose 6 phosphate (a downstream product)
PFK2
The kinase domain catalyzes formation of fructose 2,6 bisphosphate.
The phosphatase domain catalyzes the reverse reaction to fructose-6-phosphate.
PKA phosphorylates and inhibits PFK2
Compare PFK2 in the liver and muscle
liver PFK2 is phosphorylated in the kinase domain by PKA in response to glucagon or epi. This inhibits glycolysis. It has both kinase and phosphatase activity.
In the heart epi increases PFK activity because PKA will phosphorylate the phosphatase domain, inhibiting the phosphatase activity. continued production of F26BP and glycolysis
Regulation of PFK-1
inhibited by: high ATP and citrate. (associated with high energy).
activated by: AMP and ADP and fructose 2,6 bisphosphate. (associated with low energy).
Regulation of pyruvate kinase
activating: High BGL. F1,6BP. **hepatic kinase inactivated by phosphorylation. Glucagon and epi act via cAMP, PKA, to P PK. **
inhibiting: Low BGL. ATP, alanine (increased infasting mode, precursor to gluconeogenesis)
Describe the action of glucagon and epi in the liver.
inhibit PFK2, which decreases F26BP; this decreases the activity of PFK1
inhibits PK
represses synthesis of glucokinase, PFK1, PK
How does glucagon and epi inhibit glycolysis
Inhibit PFK through phosphorylation. This leads to decreased production of F2,6BP which is an allosteric inhibitor of PFK1.
Also directly inhibits PK through cAMP and P by PKA
decreased production of 3 irreversible enzymes of glycolysis.
Increased insulin, decreased cAMP, low glucagon, low epi cause
increased synthesis of glucokinase, PFK1, and PK
How does epi inhibit hepatic glycolysis but activates cardiac glycolysis.
Inhibits hepatic glycolysis through P of the kinase domain in PFK2, preventing formation of F2,6BP
Promotes glycolysis in cardiac muscle because it P and inactivates the PFK2 phosphatase domain, which leads to increased PFK2 activity and increased F26BP.
How is NAD+ regenerated
Through oxidation of NADH when pyruvate is converted to lactate via LDH enzyme. production of lactate or alcohol in an anaerobic environment.
also can use mitochondria linked shuttles: glycerolphosphate, malate aspartate. forms FADH2 and NADH. can be reoxidized in ETC, generates more ATP than LDH pathway. aerobic.
must be regenerated for glycolysis to continue
M4
Isoenzyme of LDH. Found in muscles. Prefers to catalyze conversion of pyruvate to lactate. allows for high bursts of energy.
H4
LDH isoenzyme found in heart muscle. prefers to catalyze the conversion of lactate to pyruvate. this allows for sustained production of energy. Pyruvate is then decarboxylated to acetyl-CoA and enters into the CAC
what are the different LDH and where are they found?
LDH-1 (4H) heart
LDH-2 (3H1M) circulatory system
LDH-3 (2H2M) lungs
LDH-4 (1H3M) kidney placenta pancreas
LDH-5 (4M) liver and striated muscle
What does the ratio of LDH-1 to LDH-2 in the blood tell you
LDH-1 > LDH-2 = MI
Normal ratio of lactate to pyruvate in blood
10/1
What are the allosteric inhibitors of PDH
The end products are the inhibitors: acetyl CoA, NADH
a kinase can be activated that will P and inhibit the enzyme. Factors that inhibit the kinase activate the PDH.
Identify the factors that cause PDH to be phosphorylated or dephosphorylated
Phophorylation inhibits PDH
NADH, Acetyl CoA - activate the kinase, promote phosphoryltion.
Coenzyme A, NAD+, ADP, Pyruvate: inhibit the kinase, inhibit phosphorylation
MG2+, Ca2+: promote dephosphorylation by activating the phosphatase.
What is the reaction PDH catalyzes?
Pyruvate + CoASH -> Acetyl-CoA + CO2 + NADH+ + H+.
leads to ATP production.
Identify the vitamin cofactors that participate in reaciton catalyzed by PDH
E1 - Thiamine (B1)
E2 - Pantothenate (B5)
E3 - FAD, NAD : Riboflavin (B2). Niacin (B3)
Predict the effect of a thiamine deficiency, an abnormality of PDH, or arsenic poisoning on circulating levels of lactate and pyruvate
A thiamine deficiency (B1) would cause PDH to be less active. Anything that impairs PDH won’t allow it produce acetyl-CoA. Brain and heart tissue most affected.
Aresenic poisoning- inhibits the shuttling of lipoic acid in the oxidized and reduced form. symptoms would be the same as a PDH deficiency.
**pyruvate and lactate accumulate in the blood and cause lactic acidosis. **
Lactate dehydrogenase deficiency
Cannot regenerate NAD+. glyceraldehyde-3P-dehydrogenase reaction is inhibited. NAD+ levels are inhibited during excercise.
people cannot maintain moderate levels of excercise due to not being able to use glycolysis to produce ATP needed for muscle contraction.
Predict the physiological conseqences of a genetic deficiency of fructose aldolase, and identify the foods the affected individual should avoid.
recessive genetic deficienct of aldolase B. aldolase B cleaves fructose-1-P. Deficiency results in accumulation of F1P, depletion of Pi and ATP.
Cells are damaged because they cannot maintain normal ion gradients through ATP-dependent pumps. Phosphorylted sugars are toxic to the cell.
hypoglycemia, vomiting, jaundice, hepatic failure/ cirrhosis
have low glucose level, fructose accumulation, high uric acid, high lactic acid, fructose toxicity
avoid foods with fructose.
What are the processes that require O2
reoxidation of mitochondrial NADH formed by enzyme PDH
reoxidation of cystolic NADH by mitochondrial linked shuttles: glycerol phosphate shuttle, malate spaartate shuttle.
Citric acid cycle
Decreased NADH mean
lower levels of lactate formation
Predict the physiological consequences of a genetic deficiency of either galactokinase or galactose-1-P uridyl transferase, and identify the foods the individual should avoid
accumulation of galactose activates a pathway rarely used and results in the formation of galacitol.
causes cataracts, brain damage, jaundice, enlarged liver, kidney damage, galactose uria (from build up of sugars)
remove galactose (lactose) from the diet.
pyruvate carboxylase deficiency
won’t produce oxaloacetate
leads to increased alanine, lactate, and pyruvate
developmental delay, recurrent seizures metabolic acidosis
Inputs and outputs of glycolysis
Input: glucose, 2 NAD+, 2 ATP, 4 ADP + 4 P
outputs: 2 pyruvate, 2 NADH, 2 ADP, 4 ATP
Net gain: 2 ATP
