Sample 1

A 2-year-old boy was brought into the emergency room, suffering

from severe fasting hypoglycemia. On physical examination, he
was found to have hepatomegaly. Laboratory tests indicated that
he also had hyperlacticacidemia and hyperuricemia. A liver biopsy
indicated that hepatocytes contained greater than normal
amounts of glycogen that was of normal structure. The child was
subsequently found to be missing which of the following
enzymes?

A. Glycogen synthase
B. Glycogen phophorylase
C. Glucose-6-phosphatase
D. Amylo-a(1~6)-glucosidase
E. Amylo-(1~4)-a(1~6)-transglycosylase

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 Control of glycogen phosphorylase and glycogen synthase

Glucose-6-phosphate

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 Glucose-6-phosphatase activity

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 Importance of glucose-6-phosphatase to blood glucose: liver vs skeletal muscle

Glucose-6-phosphatase

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 Amylo-a(1~6)-glucosidase and amylo-(1~4)-a(1~6)-transglycosylase activities

Amylo-a-(1~6)-glucosidase
reverses this step

Amylo-( 1 ~4}-a( 1 ~6 )-transglycosylase

reverses these steps

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Inborn errors of metabolism
involving glycogen synthesis

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 Biochemical basis of hyperlacticacidemia with hypoglycemia

Gluconeogenesis
X Glucose-6-phosphatase deficiency

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Glucose-6-phosphate in pentose phosphate pathway: basis for hyperuricemia

Uric acid

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 von Gierke Disease

Glucose-6-phosphatase

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 Sample 2

A 1-month old make showed abnormalities of the nervous system and lactic
acidosis. Enzyme assay for pyruvate dehydrogenase (PDH) activity on extracts
of cultured skin fibroblasts showed 5% of normal activity with a low
concentration (1 x 10-4 mM) of thiamin pyrophosphate (TPP), but 80% of
normal activity when the assay contained a high (0.4 mM) concentration of
TPP. Which of the following statements concerning this patient is correct?

A. Elevated levels of pyruvate in the blood reliably predict the presence of

PDH deficiency.
B. The patient is expected to show disturbances in fatty acid degradation.
C. A diet consisting of high carbohydrate intake would be expected to be
beneficial to this patient.
D. Alanine concentration in the blood is expected to be less than normal.
E. Administration of thiamin is expected to reduce his serum lactate
concentration and improve symptoms

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 Pyruvate is a gateway metabolite

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 Beta-oxidation of
fatty acids and
ketogenesis

Oxaloacetate
to Kreb’s cycle

+ pyruvate

Condensation to
Ketones

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 Role of pyruvate dehydrogenase:
Acetyl CoA formation in
glucose metabolism

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 Relationship of pyruvate to alanine

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Pyruvate dehydrogenase complex: role of thiamin coenzyme

Pyruvate dehydrogenase is the point of entry for glucose into the TCA cycle.
The mechanism of action of the pyruvate dehydrogenase complex involves the
coenzymes TPP = thiamine pyrophosphate and L = lipoic acid.

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 Sample 3

A 10-year-old boy is brought to the emergency department because of

vomiting for 6 hours. He has had excessive thirst and excretion of large
amounts of urine for 3 weeks. His pulse is 120/min and respirations are
32/min. Physical examination shows sunken eyes and diminished skin turgor.
Serum studies show hyperglycemia, ketosis, and metabolic acidosis. Urine
studies showed glucose and ketones. Which of the following sets of hepatic
findings is most likely in this patient?

Protein kinase A Phosphoprotein phosphorylase cAMP

A. ↑ ↑ ↓
B. ↑ ↓ ↑
C. ↑ ↓ ↓
D. ↓ ↑ ↑
E. ↓ ↓ ↑
F. ↓ ↓ ↓

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 Protein kinase and phosphoprotein kinase: reciprocal relationship

↑ Pyruvate kinase
↑ Glycogen synthase
↓ Glycogen phosphorylase

↑ Glycogenesis ↓ Pyruvate kinase

↑ Glycolysis ↓ Glycogen synthase
↓ Blood glucose ↑ Glycogen phosphorylase

↑ Gluconeogenesis
↑ Glyogenolysis
↑ Blood Glucose
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Relationship between
glucagon, cAMP,
protein kinase,
pyruvate kinase
Gluconeogenesis

Kreb’s cycle

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 Relationship between glucagon, cAMP, protein kinase, phosphoprotein kinase,
glycogenesis, glycogenolysis

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 Summary of metabolic
responses related to
enzyme control by
phosphorylation

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 Sample 4

An otherwise healthy 3-week-old boy is brought to the physician's

office because of jaundice and dark urine for the past 2 weeks. He
has hepatomegaly, and his stools are loose, clay-colored, and
acholic. Serum conjugated bilirubin concentration is increased.
Which of the following is the most likely cause of the
hyperbilirubinemia?

A. Defect in cholesterol synthesis

B. Deficiency in glucuronosyltransferase
C. Hemolysis
D. Inflammation of the terminal ileum
E. Obstruction of the biliary system

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 Summary of bilirubin metabolism

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 Role of cholesterol in bile synthesis

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 Sample 5

A health 28-year-old woman comes to the physician for advice on

losing weight. She is 150 cm (4 ft 11 in) and 56 kg (124 lb). Her
BMI is 25 kg/m2. Physical examination shows no other
abnormalities. The physician recommends a diet that will restrict
her daily intake by 500 kilocalories. Which of the following
processes is most likely to increase in this patient as a result of
following this diet?

A. Adipocyte glucose uptake

B. Cerebral ketone utilization
C. Hepatic lipid oxidation
D. Muscle glucose uptake
E. Resting energy expenditure

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Ketogenesis

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 Requirement for glucose uptake by adipose tissue for triglyceride synthesis

Enzyme not found in adipose tissue

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26 May 2011 27
 Intermediary metabolism

Pyruvate

Isocitrate

Kreb’s Cycle

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