FRUCTOSE METABOLISM
IT IS CONVERTED INTO GLUCOSE IN LIVER AND INTESTINE .
Fructose
ATP
1) Glyceraldehyde
F-1-PO4
ADP
ATP
2) dihydrous aceton PO4
ADP
+
Glyceraldehyde-3-PO4
F-1-PO4
Phospatase F-1,6 diPO
4
Isomerase
G-6-PO4
Phospatase
Glucose
- ESSENTIAL FRUCTOSURIA :
INHERITED DUE TO DEFICIENCY OF FRUCTOKINASE ENZYME ( BENIGN ) .
- HEREDITARY FRUCTOSE INTOLERANCE :
DEFICIENCY OF ALDOLASE B ACCUMULATION OF FRUCTOSE-1-PHOSPHATE WHICH
DECREASE PHOSPHORYLASE ENZYME OF GLYCOGENOLYSIS WHICH LEAD TO
HYPOGLYCEMIA .
NAD
CHO
|
H-C-OH
|
R
NADHph + H+
Aldose reductase
NADH+H
CH2OH
CH2OH
|
|
C=O
H-C-OH
|
dehydrogenase
|
R
R
Glucose
Sorbitol
Fructose
GALACTOSE METABOLISM
CONVERSION OF GLUCOSE INTO GALACTOSE :
UDP - Galactose ( Activedonnes) :
1- Glycolipid synth.
2- Lactose formation .
3- Mucopolysaccharide.
4- glycosaminoglycone ( GAGs ) .
GALACTOSEMIA IT IS THE INCREASE IN BLOOD GLACTOSE CONC. DUE TO
INABILITY TO METABOLIZE GALACTOSE.
CAUSES: INHERITED ENZYMES DEFICIENCY
A) GALACTOKINASE.
B) GALACTOSE-1-P-URIDYL TRANSFERASE.
C) EPIMERASE.
EFFECTS:
1- CATARACT.
2- LIVER FAILURE.
3- MENTAL RETARDATION.
Blood Glucose
Plasma Glucose level:
A. Fasting level 70-110 mg/dl.
B. one hour after meal 120-150.
C. two hours after carbohydrate meal (post prandial ) till 140.
Source of blood glucose:
1. FROM C,H,O IN DIET.
2. GLUCOGENIC COMPOUND.
3. PROPIONATE.
4. LACTATE ( IN SKELETAL MUSCLE AND RBC ).
5. AMINO ACID TRANSFERRED FROM MUSCLE TO LIVER.
6. DIETARY CARBOHYDRATE E.G. STARCH.
7. FROM LIVER GLYCOGEN THROUGH GLYCOGENOLYSIS (FOR 18 H FASTING).
8. AMINO ACID AND OTHER METABOLITES ( GLUCONEOGENESIS ).
LIVER AND KIDNEY CAN CONVERT THESE SUBSTRATES INTO GLUCOSE.
Factors that add glucose to blood
1. Carbohydrate diet.
2. Glycogenolysis.
3. Gluconeogensis.
FRUCTOSE REMOVE GLUCOSE FROM BLOOD
1. UPTAKE BY TISSUE
2. EXCRETION IN URINE
3. UTILIZATION
A. OXIDATION
B. LIPOGENESIS
C. GLUCOGENESISETABOLISM
I.
Regulation of Blood Glucose
blood glucose is maintained 70-110mg because:
hyperglycemia (increase blood glucose) can cause cerebral
dysfunction but its effect on extra cellular osmolarity.
II. hypoglycemia cause impairment of cerebral function as
brain is very
dependent on blood glucose for energy
Regulation of Blood Glucose
Regulation of glucose
1- hormonal
2- hepatic
1) Hormonal regulation:
3-renal
*INSULIN:
INSULIN IS HORMONE SECRETED BY Β-CELL OF LANGERHANS OF PANCREAS. IT IS
ONLY HORMONE WHICH REDUCE BLOOD GLUCOSE LEVEL.
1. TRANSFER GLUCOSE INTO CELLS.
2. INCREASE GLYCOGEN STORAGE.
3. STIMULATE GLUCOSE OXIDATION.
4. DECREASE GLYCOGEN BREAKDOWN.
5. DECREASE GLYCONEOGENSIS.
6. INCREASE LIPOGENSIS.
*GLUCAGON:
HORMONE SECRETED BY Α CELL OF PANCREAS INCREASE BLOOD GLUCOSE BY:
1. INCREASE GLYCOGEN BREAKDOWN BY INCREASE ADENYL CYCLASE AND INCREASE
GLYCONEOGENSIS.
2. CATECHOL AMINES : FROM SUPRARENAL MEDULLA ↑ BLOOD GLUCOSE BY :
A) ↑ GLYCOGENOLYSIS
B) ↑ GLUCOSE UP TAKE BY LIVER
3. GLUCOSTEROID AS CORTISOL : BY SUPRARENAL CORTEX .
↑ BLOOD G BY :
A) ↑ GLUCONEOGENESIS
B) ↓ OF GLUCOSE UP TAKE BY TISSUES
4. GROWTH HORMONE SECRETED FROM ANTERIOR PITUITARY GLAND
A) ↓ OF G UP TAKE BY TISSUE
B) BLOCKS INSULIN ACTION IN ALL MEMBRANES.
2) Hepatic regulation
*IN FASTING STATE:
1. IT ADD GLUCOSE TO BLOOD BY GLYCOGENOLYSIS AND
GLUCONEOGENESIS.
2. CONVERT FATTY ACID ( ACETYL COA) → KETON BODIES.
*IN FED STATE :
1. CONVERT GLUCOSE INTO GLYCOGEN.
2. CONVERT GLUCOSE INTO FATTY ACID
3) Renal regulation
Blood glucose is filtered in glomular filtrate and reabsorbed again.
* If blood glucose exceeds certain limit (180 mg/dl), glucose will increase
and exceed the capacity of tubular enzyme to reabsorb. So it will appear
in urine (called glycouria). Renal Threshold
1. HYPERGLYCEMIA:
IT IS RISE OF BLOOD GLUCOSE
CAUSES:
1. DIABETES MELLITUS
2. RECEIVE I.V. FLUIDS CONTAINING GLUCOSE
3. SEVERE STRESS
4. IN CEREBRO-VASCULAR ACCIDENTS
5. DISTURBANCE IN HYPERGLYCEMIC HORMONES
II) Hypoglycemia
If blood glucose decreased (less than 45 mg/dl), that would cause cerebral
dysfunction
if prolonged cause death (so "GLUCAGON" must be taken)
Symptoms :
Headache, Confusion, Hunger, Anxiety, Slurred speech, palpitation
Causes :
1. Fasting
2. due to organ disease :
- Pancreatic: insulinoma (Tumor)
- liver disease: hepatic carcinoma
3. Glycogen storage disease
4. Starvation
5. Adrenocortical disease (↓ epi)
STIMULATIVE:
1. DRUGS: OVERDOSE OF INSULIN
2. OVERDOSE OF ORAL HYPOGLYCEMIC AGENTS
3. LIVER POISON AS CHLOROFORM, ALCOHOL
4. POSTGASTRECTOMY (INCREASE ABSORPTION OF GLUCOSE)
5. GALACTOSEMIA
6. HEREDITARY LACTOSE INTOLERANCE
DIABETES MELLITUS
It is a state of chronic hyperglycemia (Glucose urea). Relative or absolute
deficiency of insulin hormone
Biochemical disturbance of diabetes mellitus
1) Carbohydrate:
↓Glucose uptake by tissue ↓oxidation ↑gluconeogenesis
and↑glycogenolysis ↓intracellular glucose →hunger (polyphagia)
* Increase blood glucose by:
a) Increase plasma osmolarity → dehydration.
b) Dehydration of brain cells (coma).
c) Dehydration of body cells "thirst" (polydepsia).
d) Glucose urea: frequent urination loss of vitamin B1 loss of K+,
Na+
Protein metabolism:
* Increase protein breakdown.
* Increase gluconeogensis (amino acid convert to glucose)
1.phosphatase release
2. excess breakdown of tissue protein (muscle wasting)
3. decrease antibody.
4. poor wound healing.
3) LIPID METABOLISM:
EXCESS LIPOLYSIS MOBILIZATION OF FREE FATTY ACID AND GLYCEROL TO
TISSUE AND LIVER LEAD TO:
1. LOSE WEIGHT.
2. HYPERLIPIDEMIA (ATHROSCLEROSIS)
3. FATTY LIVER
4. EXCESS KETON BODIES (KETONEMIA, KETOSIS), WHICH LEED TO KETOTIC
COMA, HYPERKALEMIA
4) MICROANGIOPATHY:
DEGENERATION AFFECTED BLOOD VESSELS OF KIDNEY AND RETINA OF EYE.
(RENAL FAILURE, BLINDNESS.
Insulin - dependent
IDDM
Non - insulin dependent
NIDDM
names
Type 1 (juvenile Diabetes)
Type 2 (adult-onset
Diabetes)
Age of onset
During childhood
After 35 old
Nutriamial stute
thin
obesity
Prevalenes
10-20% of diabetes
80-90% of digorosed
genetic
moderate
Very strong
Defect in β cells
β cell destroyed no insulin
Insulin resistance in
insulin level
Ketosis
Common
Rare
Acute complications
Keto acidosis
Hyperosmolar coma
Oral hypoglycogenic
drugs
No response
responsive
Treatment with insulin
Always necessary
Usually not reqaired
DIAGNOSIS OF DIABETES MELLITUS
1. glucose tolerance test
2. fasting blood glucose not more than 110 mg/dl
3. two hrs post (prandial) must be within the normal fasting level.
4. Glycosylated hemoglobin (HbA1C) it is a glycated protein which results
from simple non enzymatic reaction between globin part of HB and
glucose, its level in the red cells is directly proportional to the blood
glucose level at the time of formation of such cell, this level remains as
it for the whole life span of red blood cells 120 days
* It is useful for monitoring the degree of control of diabetes mellitus
during last 8-12 weeks before the test.
Normal 4 - 7.2%
5. plasma fructose amine
Albumin under go glycosylation
6. Microalbuminurea early detection of D.M. in urine by special kits.
Glucose in blood
500
diabetic
200
Renal threshold
180
100
normal
1
2
3
4
hours
Glucose tolerance curve
The Cause &
Effect of Coma
on:
Type of Coma
Diabetic Coma
Hypoglycemic Coma
Sever untreated D.M
Insulin overdose
Acetone smell
Normal
Hyperventilation
Normal
Pulse
Rapid, week
Rapid, strong
Skin
Dry
sweat
Urine glucose
Present
Absent
Urine acetone
Present
Absent
The Cause
The Effect on:
Mouth
Respiration
Diabetic coma
Hypoglycemic coma
Causes
Severe untreated D.M
Insulin overdose
Mouth
Acetone smell
Normal
Respiration
Hyperventilation
Normal
Pulse
Rapid, week
Rapid, strong
Skin
Dry
Sweet
Urine
glucose
Present
Absent
Urine
acetone
present
Absent