MMG-27 Integrated Metabolism I

1415 Test
58. Which if the following metabolic pathways take place in both cytosol and mitocho
ndria? D
A. Glycolysis and TCA
B. Glycolysis and PPP
C. Urea cycle and TCA
D. Urea cycle and gluconeogenesis
E. Urea cycle and PPP
Cholesterol synthesis also takes place in both places, as HMG-CoA synthesis is in t
he matrix, while other reactions take place in the cytosol. Keep in mind there is some
reactions taking place in sER. For example, reduction of HMG-CoA into mevalonate
and dephosphorylation of G6P into glucose is done in sER, so as elongation and de
saturation of fatty acids.

64. Which of the following is correct? C

A. Insulin activated glycogen synthase by phosphorylation
B. Insulin ......
C. Insulin inactivated glycogen synthase kinase by phosphorylation
D. Insulin inactivate glycogen phosphorylase by phosphorylation
E. Insulin receptors are GPCR

Explanation
A. phosphorylation → dephosphorylation
C. Insulin inactivates it by phosphorylation of the specific serine residues Ser21 and
Ser9 in GSK-3 isoforms α and β, respectively. (Source: wiki)
https://en.wikipedia.org/wiki/GSK-3
D. inactivate → activate
E. tyrosine receptor

1617 Test
60. Formation of glucose from glycogen is NOT an example of: D
A. Metabolism
B. Breakdown reaction
C. Catabolism
D. Anabolism
E. Hydrolysis

1718 Test
59. Which of the following description about the steroid receptor is correct: C
A DNA receptors bind to c terminal
B ligand receptors bind to the N terminal
C ligand receptors bind to C terminal
D transactive receptors bind to N terminal
E transactive receptors bind to middle of the gene
From N-terminal: Transcriptional-active, DNA-binding, ligand-binding domain

1819 Test
59. Which of the following enzyme will be activated after phosphorylation? C
A. HMG-CoA reductase
B. glycogen synthase
C. glycogen phosphorylase
D. pyruvate kinase
E. acetyl-CoA carboxylase
Glucagon, adrenaline = Low energy = Phosphorylation, and vice versa. Those active
under low energy are phosphorylated by cAMP/PKA, under glucagon and A effect.

1819 Final
20. Catecholamine is synthesized from E
A. Alanine
B. Histidine
C. Serine
D. Threonine
E. Tyrosine

2021 Test
59. Which of the following regarding intracellular receptors for hormones is correct?
C
A. Ligand binding site at N terminus
B. DNA binding site at C terminus
C. Ligand binding site at C terminus
D. Transcriptional site in middle region
E. Transcriptional site at C terminus

2021 Final
20. Epinephrine signalling in integrative metabolism involves C
A. Use of adenylate dehydrogenase
B. Use of PKC
C. Use of cAMP
D. Use of GDP
E. Use of Gq
This question only considers the effect of adrenaline on β2 and β3 receptors, so the
only possible signalling mechanism is through Gs protein, cAMP and PKA.

2122 Test
59. Which of the following enzymes is activated by insulin? C
A. Pyruvate carboxylase
B. Carnitine palmitoyltransferase I
C. Citrate lyase
D. Phosphorylase kinase
E. Acyl CoA dehydrogenase
It is impossible to recall every enzymes activated by insulin directly. My approach is t
o memorise when will insulin take effect, and what is the desired effect. Insulin is sec
reted in response to high blood glucose, in a bid to stimulate energy storing pathway
s (Glycogenesis, lipogenesis) and glycolysis to consume the blood glucose. Through
this sense, we can deduce that glucogenic enzymes like A, beta oxidative enzymes l
ike B and E, glycogenolytic enzymes like D should be inhibited in such high energy s
tate signalled by high insulin level. C is the only correct answer, as citrate lyase is re
sponsible for shunting mitochondrial acetyl CoA into cytosol for fatty acid synthesis.

2122 Final
19. Which of the following enzymes is activated by direct phosphorylation? C
A. Acetyl-CoA carboxylase
B. Glycogen synthase
C. Glycogen phosphorylase
D. HMG-CoA reductase
E. Pyruvate kinase
Similarly, keep in mind glucagon/adrenaline stands for phosphorylation, while insulin
stands for dephosphorylation. So, this question is also asknig which enzyme is activ
ated under high glucagon level, i.e. low energy state. The only appropriate answer is
C as it helps glycogenolysis to release more glucose (and G1P) into blood. Again, th
e best approach to this type of question is try to link the desired effect of hormone, w
ith the time of secretion and downstream modulations to biochemical pathways. It is
quite a mess to try writing up everything for this topic, but trying to sort the pathways
according to their time of activation and effect will help a lot.

2223 Test
59. Epinephrine signalling involves: A
A. cAMP
B. GDP
C. ADP
D. Protein kinase C
E. Activity of adenylyl transferase

EXTRA
1 Which of the following enzymes will NOT be inactivated after phosphorylation? C
A pyruvate dehydrogenase
B glycogen synthase
C glycogen phosphorylase
D pyruvate kinase
E acetyl-CoA carboxylase

2 Which of the following statements is wrong about thyroid hormone? B

A the blood concentration of T3 is lower than T4
B they are derived from serine
C T3 is more metabolically active than T4
D they are normally stored at thyroid follicles
E intracellular receptors for thyroid hormone contains the DNA binding site at the mid
dle part
T3 is the active form, while T4 is not. 90% of secreted thyroid hormone is in the form
of T4, which is converted to active T3 by 5’-deiodinase in target tissues. They are sy
nthesised from tyrosine in thyroid, and stored within thyroid follicles before release in
to bloodstream under effect of TSH.
MMG-28 Integrated Metabolism II
1516 Test
45. Which is right for hexokinase & glucokinase? A
i. Glucokinase found in liver, hexokinase is found in brain
ii. Hexokinase has a lower Km while glucokinase has a higher
iii hexokinase but not glucokinase exhibits product inhibition by g6p
iv glucokinase but not hexokinase is an inducible enzyme
A. All
B. All but i
C. i, ii
D. iii, iv
E. None of the above
Hexokinase is the housekeeping enzyme is most body cells, which exhibits product
inhibition by G6P to make sure glucose is only consumed when G6P is rapidly
consumed in glycolysis. Glucokinase is only expressed in hepatocytes, which does
not have any inhibition. Glucokinase has a higher Km (Lower affinity) and only active
under high glucose conc. (e.g. postprandial state) to stabilise blood glucose level.
(Yes I just copied the explanation from carbohydrate PP, no need to check again)

1617 Test
59. Male patient 55 years old, would like to fast for a few days to lose weight. What w
ill he depend as the alternate energy source in that period? B
A. Fatty Acid
B. Ketone bodies
C. Glycerol
D. Beta-carotene
E. Amino Acid
I think this question should be same as the one below. It is that they have forgot to m
ention brain to be precise, which can only use ketones or glucose as fuel.

[Copied from Formative Assessment 4]

A 30-year-old man has been fasting for religious reason for several days. His brain h
as reduced its need for glucose by using which of the following substances as an alt
ernate source of energy? B
A. Fatty acids
B. Ketone bodies
C. Glycerol
D. Beta carotene
E. Amino acids
Brain is an obligate glucose user for most time, i.e. mainly consumes glucose. Howe
ver, it can also consume ketone bodies in times of starvation, but not fatty acids.

1718 Final
20. Under fed state, glucokinase would E
A. convert G6P to glucose
B. convert Glycerol to glycerol 3P
C. inactive
D. increase enzymatic activity by glucagon
E. increase enzymatic activity by insulin
D is correct as insulin induces expression of glucokinase to facilitate G6P production
for synthesis of glycogen, and production of acetyl CoA for fatty acid synthesis.

1819 Test
60. During prolonged starvation, what will be the primary energy source to be used in
muscles? A
A. Fatty Acid
B. Amino acid
C. Glycerol
D. Ketone bodies
E. Glucose
Explanation
Source: (Lippincott’s illustrated reviews) Ferrier, Denise R. - Lippincott Illustrated Re
views_ Biochemistry 7th Edition 2017-Lippincott Williams & Wilkins (2017)

(This is a legit source I would say, at least more convincing than random websites.)

1920 Test
46. Early in fasting glycogen is converted to glucose in body. If liver glycogen is depl
eted, A
A. amino acid from muscle protein is degraded to blood glucose in liver
B. blood glucose level drops to 5nm until next carbohydrate intake
C. Fatty acid in adipose tissue is converted to glucose in liver
D. Lactic acid accumulated in liver is converted to glucose
E. Liver fatty acid is converted to precursor of glucose

Explanation
A is correct as protein catabolism for gluconeogenesis is the next step after all glyco
gen has been consumed. This is the last attempt for the body to provide glucose to o
bligate glucose users, and last for around 8 days. It would be fatty acids being mobili
sed next in the protein conservation phase, in which fatty acids and ketone bodies wi
ll act as the chief energy source. C and E are wrong as fatty acids and acetyl CoA ca
nnot be converted back to glucose. D is wrong as lactic acid will not accumulate in li
ver, but in muscle instead. Also, lactate production is unlikely to be high in the case
of fasting.

2021 Final
21. Which of the following is most used as the source of energy for muscles during p
rolonged fasting? D
A. Glucose
B. Glycogen
C. Amino acids
D. Fatty acids
E. Ketones

2122 Final
20. Fed state, liver glucokinase: E
A. Convert glucose 6-phosphate to glucose
B. Convert glycerol to glycerol 3-phosphate
C. Very inactive after meal
D. Show increased enzyme levels stimulated by glucagon
E. Show increased enzyme levels stimulated by insulin
At least you should be able to discard A, B and D. Glucokinase is specifically expres
sed in liver for glycolysis and glycogenesis, and hence stimulated under high glucos
e level, e.g. after meal. To serve this purpose, glucokinase is induced (Increased ex
pression) under high insulin level. Besides, fatty acid synthase, acetyl CoA carboxyla
se, citrate lyase are also induced under high insulin for lipogenesis. G6PD and malic
enzymes (Malate to pyruvate) are induced for NADPH production to support the fatty
acid synthesis.

EXTRA
1 Which of the following enzymes is inactivated when we are fasting? D
A protein kinase A
B phosphoenolpyruvate carboxykinase
C lipase in adipocytes
D acetyl-CoA carboxylase
E fructose 1,6-bisphosphatase

Protein Kinase A phosphorylates glycogen synthase to inactivate it

2 Which of the following is INCORRECT when we are in prolonged starvation? D

A glycogen storage is already used up
B catecholamines are released to stimulate ketogenesis
C the brain relies on ketone bodies and glucose as source of energy
D the breakdown of tyrosine could only produce intermediates that enter gluconeoge
nesis
E symptoms like coma could be developed

Tyrosine can be converted into fumarate (converted to oxaloacetate in TCA cycle) an

d acetoacetate, which can enter gluconeogenesis and ketogenesis respectively. Bot
h glucogenic and ketogenic.
MMG-61 Integrated Metabolism III
1718 Final
21. The hyperlipidemia in type I diabetes is mainly due to: A
A. Overactivity of hormone-sensitive lipase in adipose tissue
B. Overactivity of lipoprotein lipase
C. Inhibition of ketogenesis
D. Overexpression of insulin receptor
E. Overproduction of LDL in liver
In type I DM, there is no insulin to antagonise the effect of adrenaline and glucagon,
and hence HSL is at its full activity to promote lipolysis.

1819 Final
21. Glycation of hemoglobin (HbA1c) in normal subjects should be below: A
A. 6%
B. 7%
C. 8%
D. 9%
E. 10%
5.7% to be precise, while 6.5% is the therapeutic goal for DM management.

1920 Test
54. Adipose tissues respond to low insulin to glucagon ratio by: A
A. Activating hormone-sensitive lipase
B. Dephosphorylating interconvertible enzymes
C. Increasing amount of pyruvate kinase
D. Releasing glutamine
E. Stimulating deposition of fat
It is because hormone-sensitive lipase is activated by phosphorylation, mediated by
cAMP and protein kinase A (Thus adrenaline and glucagon). At the same time, insuli
n inhibits it by inducing dephosphorylation. This explains why diabetic ketoacidosis o
ccurs when there is low insulin but high glucagon, as there will be greatly increased l
ipolysis and β-oxidation to drive ketogenesis.

1920 final
21. Which of the following statements about glycation of hemoglobin is correct? E
A. The glycation of hemoglobin can be reversed by decrease in blood glucose conce
ntration
B. Intake of high dose of Vitamin C/E facilitate glycation of hemoglobin
C. Normal individual has HbA1c level above 6.5%
D. Normal individual has HbA1c level above 5.7%
E. HbA1c level is higher than normal for non-diabetic individual in late pregnancy

Explanation
A is clearly wrong as it is an irreversible reaction, it is only the HbA1c number could
be reversed. Intake of antioxidant (Vit C and E) will slow down the glycation. Normal
individual should be below 5.7%, while 6.5% is the therapeutic goal for diabetics to c
ontrol their blood glucose. Gestational hyperglycemia is very common and hence ha
s a higher HbA1c during pregnancy. This is due to the diabetogenic effects (Insulin r
esistance) by human somamammotropin/placental lactogen (hPL) and human place
ntal growth hormone (hPGH). However, it will gradually regress after giving birth. Yo
u will know this in HUF2 Reproductive Physiology.

2021 Test
60. What should a normal person's HbA1c levels be below? A
A. 6%
B. 7%
C. 8%
D. 9%
E. 10%

2122 Test
60. Which of the following statements about cellular mechanism of insulin resistance
is correct? A
A. Ceramide inhibits the signal transduction carried out by PI3 kinase.
B. DAG activates protein kinase A to carry out serine phosphorylation on insulin rece
ptor and insulin receptor substrate.
C. Translocation of GLUT-1 vesicles to cell surface is impaired by protein kinase A p
hosphorylation.
D. Tyrosine residue on insulin receptor is phosphorylated by protein kinase C to redu
ce effect of insulin.
E. Serine phosphorylation of PI3 kinase is involved.
Ceramide interferes with signal transduction by PI3 kinase, and A is correct. B is fals
e as it should be protein kinase C. C is false as it should be GLUT4 vesicles being i
mpaired by PKC phosphorylation. GLUT1 is ubiquitous glucose transporter in all cell
types, while only GLUT4 is regulated by insulin. D is false as it should be serine resi
due being phosphorylated by PKC. E is false, as it should insulin receptor and insuli
n receptor substrate being phosphorylated. This is the mechanism of insulin resistan
ce and please spend some time to revise it.

2122 Final
21. In type I diabetes, hyperlipidemia is mainly due to A
A. Hyperactivity of hormone-sensitive lipase in adipose tissues
B. Hyperactivity of lipoprotein lipase
C. Inhibition of ketogenesis
D. Overexpression of insulin receptor
E. Overproduction of LDL in liver
I have explained this for quite many times already. In short, there is no insulin to cou
nteract the lipolytic effect of glucagon/adrenaline in type I DM. Therefore, hormone s
ensitive lipase is overactive to keep convert TAG into FA in blood for beta oxidation
and ketogenesis. You may also think in another way, as type I DM cannot produce gl
ycogen for storage, once the blood glucose is consumed, lipolysis and ketogenesis h
ave to commence to provide alternate energy source. This shows how the fuel meta
bolism our body is precisely regulated, such that if you can consider from either way,
you will still get the same consistent answer.

2223 Test
60. What is true about type 2 diabetes compared to type 1 diabetes? C
A. It depends more on insulin injection
B. It is less associated with obesity
C. It has a higher genetic predisposition
D. Earlier age of onset, around childhood or puberty
E. More prone to ketoacidosis
A is wrong as type 1 DM features complete deficiency of insulin, while type 2 DM fea
tures insulin resistance. However, in severe type 2 DM that the pancreas cannot furt
her raise its insulin output (to overcome resistance) and becomes malfunctioned, the
patient will also need insulin injection. B is wrong as obesity is closely related to insul
in resistance. C is correct. D is wrong as it should be type 1 DM having an early ons
et but not type 2, as obesity and insulin resistance take a long time to develop. E is
wrong as DKA only occurs in low insulin/glucagon ratios. You will learn it in great det
ails in HUF2 Endocrine Physiology. The key of developing DKA is not about high glu
cagon and adrenaline levels only, but also the complete deficiency of insulin to antag
onise the lipolytic effects of glucagon and adrenaline. Hence, type 2 DM patients rar
ely develop DKA, unless they are already in advanced stage that require insulin injec
tion to control blood glucose.

Extra
1 Comparing Type I and II diabetes mellitus, D
A frequent insulin injection for Type II patients
B ketoacidosis is common in both types
C testing for circulating islet-cell antibodies can be used for Type II DM
D type II DM involves synthesis of lipotoxic precursors like ceramide
E in both types, translocation of GLUT-4 is inhibited

Explanation
A Type I
B Type I only : type II still have insulin to inhibit HMG CoA synthase
C Type I
D correct
E Type II
2 Which of the following statements about glycation of hemoglobin is INcorrect? A
A. in glycation, glucose is attached to the amino acid valine at alpha chain of hemogl
obin
B. a diabetic patient should aim to achieve a HbA1c level below 6.5%
C. hemolytic anemia would decrease the HbA1c level
D. vitamin C/E supplements could inhibits glycation
E. HbA1c level could be higher after splenectomy

Explanation
A beta chain
Remarks for Integrative Metabolism:

This is perhaps the most difficult topic in biochemistry if you ask me. I will never cho
ose the EQ from this topic as it is simply too complicated to consider. Nitrogen meta
bolism is rather separate from carbohydrate and lipid, but it still has a role when it co
mes to overall interorgan flux of metabolites. To make it simpler, it would be easier f
or you to handle regulation of individual pathways first in the previous sections, then
try to combine them with regard to their time of activation and effects. Again, it is not
about trying to memorise everything without thinking. Instead, you should try to sort t
he pathways into energy-storing and energy-releasing processes, which are then act
ivated by insulin and glucagon/adrenaline respectively. This is then related to what ki
nds of enzymes are activated by de- or phosphorylation, as insulin activates phosph
atase and glucagon/adrenaline activates protein kinase A.

It is quite difficult to observe that much details in the first attempt understanding bioc
hemistry. However, always keep in mind, no matter studying which subject, memoris
ng the pattern is always easier than memorising the facts. I am trying to introduce yo
u with the patterns of pathways and their regulation, and then you can understand a
nd recall them much more easier. Biochemistry is such a beautiful field to explore, a
s it is also something rather tangible in understanding the human body. If human stru
cture can be made visible through anatomy and histology, then human function is m
ade visible through biochemistry. We can obtain concentrations of different molecule
s through blood, urine or breath samples, so as to evaluate the functioning of differe
nt physiological or biochemical pathways. This is exactly what we are doing in Chem
ical Pathology. If you are a keen lover of chemistry, you will find this semester rather
easy to observe the interconversion of molecules. Even if you are not, try to apprecia
te the intricate networks formed by metabolites and each branch of the map is precis
ely regulated by different mechanisms. The on/off switches for each pathway are mo
nitored tightly to respond to different physiological conditions, aiming to match the de
mand of tissues. Biochemistry is not a study of individual molecules or pathway, but i
nstead understanding the whole picture illustrated with the flow of different metabolit
es. Hope you can appreciate the beauty and importance of biochemistry!