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CARBOHYDRATE
2012
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ASIDOSIS LAKTAT
• Penimbunan asam laktat didalam darah sampai kadar yg secara bermakna mempengaruhi pH,
terjadi akibat pembentukan laktat yg berlebihan.
• Kadar laktat > 5 mM & pH darah <7,2.
• Penyebab :
a. Gangguan oksidasi piruvat yg dikatalisa oleh piruvat dehidrogenase
& gangguan pada siklus TCA, biasanya berhubungan dengan
ketidakmampuan melakukan reoksidasi NADH dalam rantai respirasi
dengan kecepatan yg adekuat.
b. Pembentukan NADH yg berlebihan, misalnya intoksikasi etanol.
c. Defisiensi piruvat karboksilase.
d. Defisiensi tiamin yg parah misalnya pada peminum alkohol.
e. Intoleransi fruktosa herediter yg menimbulkan inhibisi penggunaan laktat
untuk glukoneogenesis.
f. Defisiensi glukosa 6-fosfatase yg menimbulkan peningkatan glikolisis.
g. Ion arsen/merkuri yg berikatan dengan gugus- SH dari asam lipoat sehingga
menghambat kerja piruvat dehidrogenase.
h. Defek genetik pada salah satu komponen dari kompleks piruvat
dehidrogenase.
i. Fisiologis : Akibat glikolisis anaerob yg meningkat selama olah raga.
METABOLISM OF GLYCOGEN
“GlycoGen storaGe
disease” is a Generic
term to describe a
group of inherited
disorders
characterized by
deposition of an
abnormal type or
quantity of glycogen
in the tissues.
PENTOSA PHOSPHAT PATHWAY
HMP
SHUNT vs GLIKOLISIS
AKSEPTOR
NADP+ ELEKTRON NAD+
CO2
(+) (-)
ATP
(-) (+)
RIBOSA
(+) FOSFAT (-)
• 3 molecules of glucose
6-phosphate →3 CO2 +
3 molecules C5 sugars.
• 3 molecules C5 sugars
→ 2 molecules glucose
6-phosphate + 1
molecule glycolytic
intermediate,
glyceraldehyde 3-
phosphate.
• FASE OXIDATIVE NON-
REVERSIBLE :
GLUKOSA 6-
P→RIBULOSA 5-P
MELIBATKAN
DEHIDROGENASE &
DEKARBOKSILASE→NA
DPH
• FASE NON-OXIDATIVE
REVERSIBLE :
RIBULOSA 5-
P→GLUKOSA 6-P
MELIBATKAN 2 GROUP
ENZIM :
TRANSKETOLASE &
TRANSADOLASE→RIBO
SA
Genetic deficiency of glucose 6-phosphate dehydrogenase,the first enzyme of the pentose
phosphate pathway, is a major cause of hemolysis of red blood cells, resulting in hemolytic
anemia.
(*Not found in liver) • Fructose undergoes more
rapid glycolysis, because it
bypasses the regulatory
step catalyzed by
phosphofructokinase
• Fructokinase activity is not
affected by fasting or by
insulin
METABOLISME FRUKTOSA
Aldolase A is found in all tissues, whereas
aldolase B is the predominant form in liver.
FRUKTOSA LOADING
©2006
Buse MbyGAmerican Physiological
Am J Physiol Society Metab 2006;290:E1-E8
Endocrinol
DIIT GLYCOGENOLYSIS
- +
BLOOD
GLUCOSE
LEVEL GLUCAGON
CATECHOLAMINES
- GH
CORTISOL
GLUCONEOGENESIS +
FASTING
HIGH CARBOHYDRATE
DIIT BLOOD GLUCOSE
GLUCOSE LEVEL INCREASE
LEVEL
(80-100 mg/dl) 30 MINUTE – 1 HOUR (120-140 mg/dl)
PLASMA
GLUCOSE
CONCENTRATION
Diagnosis of diabetes mellitus & glucose intolerance
condition Diagnostic criteria (mg/dl) comments
Normal fasting plasma glucose < 110
Diabetes mellitus *
Criterion 1 Random plasma glucose ≥ 200 **
Criterion 2 Fasting plasma glucose ≥126
Criterion 3 2 h value during OGTT ≥ 200
Hyper glycemia
blocked
PARP inhibitors
Copyright ©M2011
Brownlee American
Diabetes Diabetes Association, Inc.
2005;54:1615-1625
results in the depletion of NADPH, a decrease in
cellular reduced glutathione levels, and increased
oxidative stress. Sorbitol↑→osmotic stress ↑→
cataract diabetic
transketolase activators
(benfotiamine)
Somogyi Effect
Rebound hyperglycemia
Counterregulatory hormones activate
gluconeogenesis and glycogenolysis
Hormones supress insulin 12-48 hours
Also influenced by excessive carb intake
Dawn Effect
Dawn effect is defined as an increase in the blood sugar in the morning
and is typically invoked in the context of diabetes. It is different from
Chronic Somogyi rebound in that dawn effect is not associated with
nocturnal hypoglycemia.
It is possible that dawn effect is caused by the release of counterregulatory
hormones such as cortisol, glucagon, epinephrine, all of which can signal
the liver to release glucose. In most of the cases, there is no need to change
insulin dosing of patients who encounter dawn effect.
The dawn phenomenon is more common than the Somogyi effect.
To diagnose these phenomena, it is useful to measure plasma glucose levels
for several nights between 3 a.m. and 5 a.m. or use a continuous glucose
monitoring system.
Dawn Effect vs Somogyi Effect