Gluconeogenesis, HMP Shunt Flashcards
Gluconeogenesis irreversible enzymes
- Pyruvate carboxylase
- Phosphoenoyruvate carboxykinase
- Fructose-1,6-bisphosphatase
- Glucose-6-phosphate
Pyruvate carboxylase reaction and location
Pyruvate + CO2+ATP –> oxaloacetate
Mitochondia
Pyruvate carboxylase is activated by
Acetyl coa
Pyruvate carboxylase requirement
Biotin
ATP
Phosphoenolpyruvate carboxykinase requirements
GTP
Phosphoenolpyruvate carboxykinase reaction and location
Oxaloacetate to phosphoenolpyruvate
cytosol
Fructose -1,6- bisphosphatase reaction and location
Fructose -1,6-BP–>fructose-6-P
cytosol
Fructose -1,6- bisphosphatase regulation
Citrate+
Fructose 2,6-BP-
AMP -
ATP +
Glucose-6-phosphatase reaction
Glucose -6-P–>glucose
Glucose-6-phosphatase LOCATION / AND ORGAN
ENDOPLASMIC RETICULUM
PRIMARILY IN LIVER
Gluconeogenesis serves
To maintain euglycemia during fasting
Gluconeogenesis tissues
Liver(primary)
Kidney
Intestinal epithelium
Deficiency of key gluconeogenic enzymes cause
Hypoglycemia
Muscle - gluconeogenesis
no –> lacks glucose -6 phosphatase
fatty acids/gouconeogenesis
Even chain fatty acids –> cannot produce new, since they yield only acetyl-CoA equivalents
Odd-chain fatty acids –> yield one propionyl-CoA during metabolism, which can enter TCA (as succinyl-CoA), undergo gluconeogenesis
Propionyl-CoA can enter TCA cycle as
Succinyl - CoA
Odd-chain fatty acids/gluconeogenesis
They yield one propionyl-CoA during metabolism, which can enter TCA (as succinyl-CoA), undergo gluconeogenesis
Source of NADPH
HMP shunt
HMP
Pentose phosphate pathway
HMP provides a source of
NADPH
HMP provides a source of from abundantly available
Glucose-6-P
HMP yields
- NADPH
- Ribose for nucleotide synthesis
- Glycolytic intermediates
How many pathways for HMP shunt
2.
Oxidative and nonoxidative
NADPH function
- Glutathione reductase
- Cytochrome P-450
- Respiratory burst
- Anabolic process (steroid and farry acids synthesis)
Location of of oxidative HMP shunt
Cytoplasm
Location of nonoxidative HMP shunt
Cytoplasm
ATP/HMP shunt
NO ATP IS USED OR PRODUCED IN HMP SHUNT
Is oxidative HMP shunt reversible or irreversible
Irreversible
Sites of HMP shunt (organs)
Sites of fatty acid or steroid synthesis (lactating mammary glands, liver, adrenal glands), RBCs
Is nonoxidative reaction reversible or irreversible
Reversible
HMP shunt rate determining enzyme
G6PD
G6PD regulators
NADP+
NADPH-
Oxidative HMP shunt reaction
Glucose-6-P + 2NADP –> CO2 + 2NADPH + Ribulose-5-P (G6PD/irreversible)
G6PD deficiency cellular features
- Heinz bodies
2. Bite cells
Most common enzyme deficiency / mode of inheritance / PURPOSE
G6PD / XR
increases
Bite cells
Result from the phagocytic removal of Heinz bodies (RBCs) by splenic macrophages
Most common enzyme deficiency / mode of inheritance
G6PD / XR
increases
Heinz bodies
Oxidized/denaturated Hemoglobin precipitated within RBCs
G6PD deficiency anemia - mechanism
Decreased NADPH in RBCs leads to hemolytic anemia due to poor RBC defense against oxidizing agents
Factors that precipitate hemolysis in G6PD deficiency
- Drugs: sulfonamides, primaquine, antituberculosis
- Fava beans
- Infections (ROS generated via inflammatory response can diffuse into RBCs and cause oxidative damage
Fructose metabolism
Fructose + ATP –> Fructose-1-P + ADP (Fructokinase)
Fructose-1-P –> Dihydroxyacetone-P + Glyceraldehyde (Aldolase B):
- Dihydroxyacetone-P –> Glyceraldehyde-3-P –> glycolisis
- Glyceraldehyde + ATP –> Glyceraldehyde-3-P (Trise kinase) –> glycolisis
- Glyceraldehyde + NADH –> Glycerol
Fructokinase reaction
Fructose + ATP –> F1P+ ADP
Is Essential fructosuria a severe disease?
No. It is a benign symptomatic condition
Essential fructosuria - mechanism and mode of inheritance
Defect in fructokinase
AR
Essential fructosuria pathophysiology
Defect in fructokinase (AR)
Fructose is not trapped in cells –> fructose in blood and urine
Essential fructosuria findings
Fructose appears in blood and urine
Fructose intolerance mode of inheritance
AR
Disorder of fructose metabolism vs galactose metabolism according symptoms
Disorder of fructose metabolism cause milder symptoms
aldolase B reaction
Fructose-1-P to glyceraldehyde or dihydroxyacetone -P
Fructose intolerance - deficiency of
Hereditary deficiency of aldolase B
Fructose intolerance pathophysiology
Hereditary deficiency of aldolase B. Fructose-1-P accumulates causing decreased availability of phosphate –> inhibition of glycogenolysis and glyconeogenesis
Fructose intolerance inhibits
- Glycogenolysis
2. Gluconeogenesis
Symptoms of fructose intolerance present following
CONSUMPTION of fruit, juice, honey
Fructose intolerance/urine
- Urine dipstick - (test for glucose only)
2. Reducing sugar can be detected in the urine (nonspecific for inborn errors of carbohydrate metabolsim)
Fructose intolerance symptoms
- Hypoglycemia
- Jaundice
- Cirrhosis
- Vomiting
Sucrose sequence
Glucose and fructose
Fructose intolerance treatment
Reduce fructose and sucrose (glucose and fructose) intake
Glyceraldehyde to glyceraldehyde-3-P - reaction
Triose kinase + ATP
Galactokinase deficiency
Hereditary deficiency of galacktokimase
Galactose metabolism
Galactose –>
a. Galactiol (Aldose reductase)
b. Galactose-1-P (Galactokinase) –> Glucose-1-P (Uridiltransferalase, 4-epimerse reverse it) –> Glycolysis/glycogenesis
Galactokinase deficiency pathophysiology
Galactitol (reduction product of galactose) accumulates if galactose present in diet
Is Galactokinase deficiency a severe condition / mode of inheritance
No. It is a relatively mild condition
AR
Galactokinase deficiency sympoms
- Galactose in urine and blood
- Infantile cataracts
- May initially present as failure to track objects or to develop a social smile
Classic galactosemia mode of inheritance
AR
Classic galactosemia pathophysiology
Damaged is cause by accumulation of toxic substances (including galactitol, which accumulate in the lens of the eye)
Classic galactosemia
Absence of galactose-1-phosphate uridyltransferase
Classic galactosemia treatment
Exclude galactose and lactose (galactose and glucose) fro diet
Lactose sequence
Galactose and glucose
Classic galactosemia symptoms
- Failure to thrive
- Jaundice
- Hepatomegaly
- Infantile cataracts
- Intellectual disability
- E. Coli sepsis in neonates
- Pi depletion (in most serious defect)
Galactose/glycolisis/glycogenesis
Galactose–>galactose-1-P(galactokinase) –> glucose-1-P (uridyltransferase) –> glycolysis/glyconeogenesis
Lactase deficiency? types?
Insufficient lactase enzyme–> dietary lactose intolerance
types: 1ry, 2ry, congenital
Lactase function
It is on the brush border and digests lactose (human and cow milk) into glucose and galactose
Secondary lactose deficiency
Loss of brush border due to gastroenteritis (rotavirus), autoimmune etc
Primary lactose deficiency
Age dependent decline after childhood (absence of lactase-persistent allele, common in people of Asia, Africa, native american descent
lactose deficiency symptoms
Bloating, cramps, flatulence, osmotic diarrhea
Congenital lactose deficiency
Rare, due to defective gene
Lactase deficiency treatment
Avoid dairy products
Add lactase pills to diet
Lactose free milk
Glucose alcohol counterpart
Sorbitol
Lactase intolerance lab findings
Stool-low ph
Breath- high hydrogen
Intestinal biopsy - normal with hereditary
Alternative method of trapping glucose in the cell
Convert it to sorbitol (its alcohol counterpart)
Glucose to sorbitol reaction
Aldose reductase and NADPH
Sorbitol to fructose
Sorbitol dehydrogenase + NAD
Tissues with sorbitol dehydrogenase
Liver, ovaries, seminal vesicles
Tissues without sorbitol dehydrogenase
Scwann cells, retina, kidneys has only aldose reductase
Lens has primarily aldose reductase
G6PD deficiency is mom common in black or white
Black
Insufficient amount of sorbitol reductase consequences
Intracellular accumulation –> osmotic damage (cataracts, retinopathy, peripheral neuropathy) seen in chronic hyperglycemia in diabetes
G6PD deficiency evolutionary benefits
Malarial resistance
MCC of hemolyisis in G6PD anemia
infection
