Gluconeogenesis, HMP Shunt Flashcards Preview

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Flashcards in Gluconeogenesis, HMP Shunt Deck (88):
1

Gluconeogenesis irreversible enzymes

1. Pyruvate carboxylase
2. Phosphoenoyruvate carboxykinase
3. Fructose-1,6-bisphosphatase
4. Glucose-6-phosphate

2

Pyruvate carboxylase reaction and location

Pyruvate + CO2+ATP --> oxaloacetate
Mitochondia

2

Pyruvate carboxylase is activated by

Acetyl coa

3

Pyruvate carboxylase requirement

Biotin
ATP

4

Phosphoenolpyruvate carboxykinase requirements

GTP

5

Phosphoenolpyruvate carboxykinase reaction and location

Oxaloacetate to phosphoenolpyruvate
cytosol

7

Fructose -1,6- bisphosphatase reaction and location

Fructose -1,6-BP-->fructose-6-P
cytosol

8

Fructose -1,6- bisphosphatase regulation

Citrate+
Fructose 2,6-BP-
AMP -
ATP +

8

Glucose-6-phosphatase reaction

Glucose -6-P-->glucose

9

Glucose-6-phosphatase LOCATION / AND ORGAN

ENDOPLASMIC RETICULUM
PRIMARILY IN LIVER

10

Gluconeogenesis serves

To maintain euglycemia during fasting

11

Gluconeogenesis tissues

Liver(primary)
Kidney
Intestinal epithelium

12

Deficiency of key gluconeogenic enzymes cause

Hypoglycemia

13

Muscle - gluconeogenesis

no --> lacks glucose -6 phosphatase

15

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

15

Propionyl-CoA can enter TCA cycle as

Succinyl - CoA

16

Odd-chain fatty acids/gluconeogenesis

They yield one propionyl-CoA during metabolism, which can enter TCA (as succinyl-CoA), undergo gluconeogenesis

17

Source of NADPH

HMP shunt

18

HMP

Pentose phosphate pathway

19

HMP provides a source of

NADPH

20

HMP provides a source of from abundantly available

Glucose-6-P

21

HMP yields

1. NADPH
2. Ribose for nucleotide synthesis
3. Glycolytic intermediates

22

How many pathways for HMP shunt

2.
Oxidative and nonoxidative

23

NADPH function

1. Glutathione reductase
2. Cytochrome P-450
3. Respiratory burst
4. Anabolic process (steroid and farry acids synthesis)

24

Location of of oxidative HMP shunt

Cytoplasm

25

Location of nonoxidative HMP shunt

Cytoplasm

26

ATP/HMP shunt

NO ATP IS USED OR PRODUCED IN HMP SHUNT

27

Is oxidative HMP shunt reversible or irreversible

Irreversible

28

Sites of HMP shunt (organs)

Sites of fatty acid or steroid synthesis (lactating mammary glands, liver, adrenal glands), RBCs

29

Is nonoxidative reaction reversible or irreversible

Reversible

30

HMP shunt rate determining enzyme

G6PD

31

G6PD regulators

NADP+
NADPH-

32

Oxidative HMP shunt reaction

Glucose-6-P + 2NADP --> CO2 + 2NADPH + Ribulose-5-P (G6PD/irreversible)

33

G6PD deficiency cellular features

1. Heinz bodies
2. Bite cells

34

Most common enzyme deficiency / mode of inheritance / PURPOSE

G6PD / XR
increases

35

Bite cells

Result from the phagocytic removal of Heinz bodies (RBCs) by splenic macrophages

36

Most common enzyme deficiency / mode of inheritance

G6PD / XR
increases

37

Heinz bodies

Oxidized/denaturated Hemoglobin precipitated within RBCs

39

G6PD deficiency anemia - mechanism

Decreased NADPH in RBCs leads to hemolytic anemia due to poor RBC defense against oxidizing agents

40

Factors that precipitate hemolysis in G6PD deficiency

1. Drugs: sulfonamides, primaquine, antituberculosis
2. Fava beans
3. Infections (ROS generated via inflammatory response can diffuse into RBCs and cause oxidative damage

41

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

41

Fructokinase reaction

Fructose + ATP --> F1P+ ADP

42

Is Essential fructosuria a severe disease?

No. It is a benign symptomatic condition

43

Essential fructosuria - mechanism and mode of inheritance

Defect in fructokinase
AR

44

Essential fructosuria pathophysiology

Defect in fructokinase (AR)
Fructose is not trapped in cells --> fructose in blood and urine

45

Essential fructosuria findings

Fructose appears in blood and urine

46

Fructose intolerance mode of inheritance

AR

48

Disorder of fructose metabolism vs galactose metabolism according symptoms

Disorder of fructose metabolism cause milder symptoms

48

aldolase B reaction

Fructose-1-P to glyceraldehyde or dihydroxyacetone -P

49

Fructose intolerance - deficiency of

Hereditary deficiency of aldolase B

50

Fructose intolerance pathophysiology

Hereditary deficiency of aldolase B. Fructose-1-P accumulates causing decreased availability of phosphate --> inhibition of glycogenolysis and glyconeogenesis

51

Fructose intolerance inhibits

1. Glycogenolysis
2. Gluconeogenesis

53

Symptoms of fructose intolerance present following

CONSUMPTION of fruit, juice, honey

54

Fructose intolerance/urine

1.Urine dipstick - (test for glucose only)
2. Reducing sugar can be detected in the urine (nonspecific for inborn errors of carbohydrate metabolsim)

55

Fructose intolerance symptoms

1. Hypoglycemia
2. Jaundice
3. Cirrhosis
4. Vomiting

55

Sucrose sequence

Glucose and fructose

56

Fructose intolerance treatment

Reduce fructose and sucrose (glucose and fructose) intake

57

Glyceraldehyde to glyceraldehyde-3-P - reaction

Triose kinase + ATP

58

Galactokinase deficiency

Hereditary deficiency of galacktokimase

60

Galactose metabolism

Galactose -->
a. Galactiol (Aldose reductase)
b. Galactose-1-P (Galactokinase) --> Glucose-1-P (Uridiltransferalase, 4-epimerse reverse it) --> Glycolysis/glycogenesis

60

Galactokinase deficiency pathophysiology

Galactitol (reduction product of galactose) accumulates if galactose present in diet

61

Is Galactokinase deficiency a severe condition / mode of inheritance

No. It is a relatively mild condition
AR

63

Galactokinase deficiency sympoms

1. Galactose in urine and blood
2. Infantile cataracts
3. May initially present as failure to track objects or to develop a social smile

63

Classic galactosemia mode of inheritance

AR

64

Classic galactosemia pathophysiology

Damaged is cause by accumulation of toxic substances (including galactitol, which accumulate in the lens of the eye)

65

Classic galactosemia

Absence of galactose-1-phosphate uridyltransferase

66

Classic galactosemia treatment

Exclude galactose and lactose (galactose and glucose) fro diet

67

Lactose sequence

Galactose and glucose

68

Classic galactosemia symptoms

1. Failure to thrive
2. Jaundice
3. Hepatomegaly
4. Infantile cataracts
5. Intellectual disability
6. E. Coli sepsis in neonates
7. Pi depletion (in most serious defect)

69

Galactose/glycolisis/glycogenesis

Galactose-->galactose-1-P(galactokinase) --> glucose-1-P (uridyltransferase) --> glycolysis/glyconeogenesis

71

Lactase deficiency? types?

Insufficient lactase enzyme--> dietary lactose intolerance
types: 1ry, 2ry, congenital

72

Lactase function

It is on the brush border and digests lactose (human and cow milk) into glucose and galactose

72

Secondary lactose deficiency

Loss of brush border due to gastroenteritis (rotavirus), autoimmune etc

73

Primary lactose deficiency

Age dependent decline after childhood (absence of lactase-persistent allele, common in people of Asia, Africa, native american descent

74

lactose deficiency symptoms

Bloating, cramps, flatulence, osmotic diarrhea

75

Congenital lactose deficiency

Rare, due to defective gene

76

Lactase deficiency treatment

Avoid dairy products
Add lactase pills to diet
Lactose free milk

77

Glucose alcohol counterpart

Sorbitol

78

Lactase intolerance lab findings

Stool-low ph
Breath- high hydrogen
Intestinal biopsy - normal with hereditary

79

Alternative method of trapping glucose in the cell

Convert it to sorbitol (its alcohol counterpart)

80

Glucose to sorbitol reaction

Aldose reductase and NADPH

81

Sorbitol to fructose

Sorbitol dehydrogenase + NAD

83

Tissues with sorbitol dehydrogenase

Liver, ovaries, seminal vesicles

84

Tissues without sorbitol dehydrogenase

Scwann cells, retina, kidneys has only aldose reductase
Lens has primarily aldose reductase

84

G6PD deficiency is mom common in black or white

Black

85

Insufficient amount of sorbitol reductase consequences

Intracellular accumulation --> osmotic damage (cataracts, retinopathy, peripheral neuropathy) seen in chronic hyperglycemia in diabetes

87

G6PD deficiency evolutionary benefits

Malarial resistance

88

MCC of hemolyisis in G6PD anemia

infection