Diseases

Question 1

Diabetic pathologies and sorbitol

Answer 1

• accumulation of sorbitol in tissues that lack sorbital DH in diabetics: lens (causing cataracts), retina, kidney and nerve cells
• Glu -[aldose reductase]-> sorbitol - [sorbital DH]-> fructose

Question 2

Fructose intolerance

Answer 2

• lack of liver-specific (F-1-P) aldolase that turns F-1-P to glyceraldehyde-3-P (-> gluconenogensis or glycolysis)
• F-1-P accumulates,
• its production depletes Pi stores
• F-1-P inhibits glycogen phosphorylase -> no glycogen breakdown -> hypoglycemia

Question 3

Galactosemia

Answer 3

• lack of uridyl transferase, which takes the P from Gal-1-P to produce G-6-P
• galactol accumulates -> cataracts

Question 4

G6PDH deficiency

Answer 4

• pentose phosphate pathway
• supplies (such as erythrocytes) (NADPH).
• The NADPH in turn maintains the level of glutathione in these cells that helps protect the red blood cells against oxidative damage.
• Of greater quantitative importance is the production of NADPH for tissues actively engaged in biosynthesis of fatty acids and/or isoprenoids, such as the liver, mammary glands, adipose tissue, and the adrenal glands. G6PD reduces nicotinamide adenine dinucleotide phosphate (NADP) to NADPH while oxidizing glucose-6-phosphate.[1]
• genetic deficiency of G6PD predisposes to non-immune hemolytic anemia .
• attacks stimulated by stress, drugs, foods, and chemical agents
• treat with transfusion, avoiding oxidative stress

Question 5

von Gierke’s

Answer 5

• Glucose-6-phosphatase deficiency
• Normally glycogenolysis produces G-6-P, which is then dephosphorylated to produce glucose.
• lack of the enzyme leads to glycogen accumulation -> liver storage disease
• Can’t export glucose from liver -> hypoglycemia
• glycogen storage disease
• brain damage, growth retardation
• treat with frequent meals

Question 6

McArdle’s syndrome

Answer 6

• glycogen phosphorylase deficiency in muscle/liver
• again, can’t break down glycogen -> gylcogen storage disease
• with glucagon (LV) or epinephrine (any cell) ⇒ G protein ⇒ AC ⇒ cAMP ⇒ PKA ⇒ phosphorylase kinase ⇒ glycogen phosphorylase ⇒ turns glycogen into glucose-1-P ⇒ glucose-6-P ⇒ exported from cell as glucose
• McArdle -> Muscle damage

Question 7

Anderson disease

Answer 7

• glycogen branching enzyme deficiency
• glycogen has very long branches and scaring of the liver
• failure to thrive

Question 8

Cori’s disease

Answer 8

• glycogen debranching deficiency
• gylogen storage disease
• hepatomegaly, hypoglycemia
• managed by small meals

Question 9

Alcohol

Answer 9

• Causes hypoglycemia, especially with starvation
• alcohol is metabolized by alcohol DH
• this enzyme needs NAD+, and thus it uses up the NAD+ that is normally used by LDH in the liver to convert lactate to pyruvate for gluconeogenesis -> hypoglycemia
• Fattening
• alcohol metabolism provides acetyl coA for Kreb’s cycle, so we don’t need to use FA breakdown to produce acetyl coA