Bioenergetics and Integrated Metabolism

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Multiple Choice

What is the main source of ATP?

• Glycolisis

• Kreb's cylce

• Oxidative phosphorilation

TRICARBOXYIC ACID CYCLE

= CITRIC ACID CYCLE

= KREB’S CYLE

ACETYL CO-A (2C)

+ OXALOACETATE (4C)

= CITRATE (6C)

which goes through the cycle

THE CYCLE ENDS UP WITH:

1 OAA → used in the next cycle

1 GTP → a high energy substance

3 NADH AND 1 FADH 2

→ will act as reducing agents in

the electron transpor t chain

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OXYDATIVE PHOSPHORYLATION

1. CARBS OF PHYSIOLOGICAL SIGNIFICANCE

Carbohydrates (saccharides) classification

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Glucose transport in the small intestine

• Glucose and Na+ bind to different sites on a Na+-glucose symporter located at the

apical surface. Na+ moves into the cell down its electrochemical gradient and
“drags” glucose with it. Therefore, the greater the Na+ gradient, the more glucose
enters; and if Na+ in extracellular fluid is low, glucose transport stops. To maintain a
steep Na+ gradient, this Na+-glucose symporter is dependent on gradients
generated by the Na+-K+-ATPase, which maintains a low intracellular Na+
concentration.

• The transcellular movement of glucose involves one additional component, a

uniport that allows the glucose accumulated within the cell to move across the
basolateral membrane and involves a glucose uniporter (GLUT2).

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Glucose transport in the small intestine

• The treatment of severe cases of diarrhea (such as is found in cholera) makes use of

the above information. In cholera, massive amounts of fluid can be passed as watery
stools in a very short time, resulting in severe dehydration and possibly death.

• Oral rehydration therapy, consisting primarily of NaCl and glucose, has been

developed by the World Health Organization (WHO). The transport of glucose and
Na+ across the intestinal epithelium forces (via osmosis) movement of water from
the lumen of the gut into intestinal cells, resulting in rehydration. Glucose alone or
NaCl alone would not be effective.

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The transcellular movement of
glucose in an intestinal cell.

Glucose follows Na+ across the luminal epithelial
membrane. The Na+ gradient that drives this
symport is established by Na+-K+ exchange, which
occurs at the basolateral membrane facing the
extracellular fluid compartment via the action of the
Na+-K+-ATPase. Glucose at high concentration within
the cell moves “downhill” into the extracellular fluid
by facilitated diffusion (a uniport mechanism), via
GLUT2 (a glucose transporter). The sodium-glucose
symport actually carries 2 Na+ for each glucose.

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3. GLUCOSE METABOLISM

GLUCOSE METABOLISM OVERVIEW

• Glucose resulting from the digestion of carbohydrates are absorbed via the

hepatic portal vein, that sends all of the absorbed glucose to the liver.

• The liver has the role of regulating the blood concentration of these water-

soluble metabolites by taking up a small or large fraction of that which is
delivered into the portal vein, thus removing a variable portion of the
absorbed glucose, before they enter the systemic circulation.

• The uptake of glucose is a regulated process.

Match

Match the following

• Glucose

• Amino acids

• Fatty acids

Glycolysis

Deamination

Beta oxidation

• Glycolysis

• Deamination

• Beta oxidation

Multiple Choice

Mirna, seorang perempuan berusia 27 tahun, dilarikan ke UGD RS karena mengalami kejang-kejang dan penurunan kesadaran setelah mengkonsumsi kopi yang dipesan temannya di sebuah kafe. Mirna dinyatakan meninggal tidak lama kemudian. Hasil pemeriksaan menunjukkan adanya sianida di lambung dan kopi Mirna. Bagian manakah dari proses respirasi seluler yang dihambat oleh racun tersebut?

• Complex I

• Complex II

• Complex III

• Complex IV

• ATP synthase

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O2

present

O2

absent

Krebs cycle

Acetyl-CoA

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Curved arrows indicate
forward and reverse
reactions catalyzed by
differentenzymes.

Acetyl-CoA

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Interconversion of
pyruvate and lactate

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Pyruvate to Acetyl CoA: (ireversible)

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Mechanism of action of the PYRUVATE DEHYDROGENASE complex.

All the coenzymes of the complex (except for lipoic acid, L) are derived from vitamins.
TPP (thiamine pyrophosphate) is from thiamine
FAD(H2) (flavin adenine dinucleotide) from riboflavin
NAD(H) (nicotinamide adenine dinucleotide) from niacin
CoA (coenzyme A) from pantothenic acid

GLUCONEOGENESIS

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2

Gluconegogenesis

• Producing glucose from non-sugar substrates.
• It is the reverse of glycolysis
• Remember: glycolysis has 3 irreversible steps

–Glucose to glucose-6-phosphate by hexokinase
–Fructose -6-phosphateto fructose-1,6-biphosphate by phosphofructokinase
–Phosphoenol pyruvate (PEP) to pyruvate by pyruvate kinase

• The 3 irreversible reactions are catalyzed by enzymes different from the

ones used in glycolysis.

• The reconversion of pyruvate to phosphoenol-pyruvate (PEP) requires

two reactions.

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Multiple Choice

Seorang pasien berusia 16 tahun dengan diabetes melitus tipe 1 dirawat di rumah sakit dengan kadar glukosa darah 400 mg/dL. Pasien kemudian diberi infus insulin. Satu jam setelah infus insulin dimulai, kadar glukosa darahnya menurun hingga 320 mg/dL. Satu jam kemudian, menjadi 230 mg/dL. Apa yang disebabkan oleh insulin sehingga kadar glukosa pasien menurun?

A

• Stimulasi pengangkutan glukosa melintasi membran sel hati dan otak

• Stimulasi konversi glukosa menjadi glikogen dan triasilgliserol di hati

• Penghambatan sintesis badan keton dari glukosa darah

• Stimulasi glikogenolisis di hati

• Penghambatan konversi glikogen otot menjadi glukosa darah

Note

• Acetyl coenzyme A (CoA) and compounds that give rise only to acetyl

CoA (for example, acetoacetate and amino acids such as lysine and
leucine) cannot give rise to a net synthesis of glucose.

• This is due to the irreversible nature of the pyruvate dehydrogenase

(PDH) reaction, which converts pyruvate to acetyl CoA. These
compounds give rise instead to ketone bodies and are, therefore,
termed ketogenic.

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REACTIONS UNIQUE TO GLUCONEOGENESIS

• Most glycolytic reactions are reversible and are used in the

synthesis of glucose from lactate or pyruvate.

• However, three of the reactions are irreversible and must be

circumvented by four alternate reactions that energetically
favor the synthesis of glucose.

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Gluco-
neo-

genesis

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GLYCOGEN METABOLISM
(Glycogenesis & Glycogenolysis)

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3

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The pentose phosphate pathway

• = hexose monophosphate shunt
• occurs in the cytosol of the cell
• includes two irreversible oxidative reactions, followed by a

series of reversible sugar-phosphate interconversions

• No adenosine triphosphate (ATP) is directly consumed or

produced in the cycle.

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The pentose phosphate pathway

For each glucose 6-phosphate molecule entering the oxidative
part of the pathway:
• Carbon 1 of glucose 6-phosphate is released as CO2
• two NADPHs are produced

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• Kennelly P.J., & Botham K.M., & McGuinness O.P., & Rodwell V.W., & Weil P(Eds.),

(2023). Harper's Illustrated Biochemistry, 32e. McGraw Hill.

• Lieberman and Ricer - Biochemistry, Molecular Biology, and Genetics (2013)
• Melkonian EA, Asuka E, Schury MP. Physiology, Gluconeogenesis. [Updated 2022

May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing;
2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK541119/

• Aziz H, Mohiuddin SS. Biochemistry, Hexose Monophosphate Pathway. [Updated

2022 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls
Publishing; 2023 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK551687/

• Oliphant, K., Allen-Vercoe, E. Macronutrient metabolism by the human gut

microbiome: major fermentation by-products and their impact on host health.
Microbiome 7, 91 (2019). https://doi.org/10.1186/s40168-019-0704-8

• Materi kuliah dr. Seto Priyambodo, M.Sc. Metabolisme Karbohidrat. 2022.

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