All Important Things About Carbohydrate Metabolism - NEET PG Biochemistry

Carbohydrate metabolism is an important topic for the NEET PG exam because it is a fundamental aspect of human physiology and biochemistry. It plays a crucial role in the pathophysiology of various diseases such as diabetes, obesity, and metabolic syndrome. A deep understanding of the mechanisms involved in carbohydrate metabolism is essential for the diagnosis, treatment, and management of these conditions.

Additionally, the NEET PG exam is a comprehensive test that covers all aspects of medical science, and carbohydrate metabolism is a fundamental topic that is tested in biochemistry and endocrinology. Hence, a strong understanding of the topic is crucial for success in the NEET PG exam.

In this blog post, we’ll be covering important details pertaining to this topics. Read on.

GLYCOLYSIS

Glycolysis aka EMP pathway (Embden Meyerhof pathway) has 3 irreversible steps

1. Hexokinase
2. PFK -1
3. Pyruvate kinase (SLP)

Another SLP step is PG kinase step 

Inhibitor of Glycolysis include -

• Iodoacetate → inhibits glyceraldehyde-3-P dehydrogenase
• Arsenite → inhibits glyceraldehyde-3-P dehydrogenase 
• Na Fluoride→ inhibits Enolase (used in blood glucose estimation) 

Important Information

• When arsenite inhibits glycolysis, then no ATP is produced but glycolysis continues, and pyruvate is formed normally.

LINK REACTION

• Enzyme involved - PDH complex
• Site: Mitochondria

• In B1 deficiency (Beri-Beri) lactic acidosis will occur due to excess pyruvate converting into lactate in cytoplasm.
• Link reaction is irreversible
• Fats cannot be converted to carbohydrates as acetyl CoA can never be converted to pyruvate 

Also Read : An easy approach to controversial questions in Biochemistry

TCA CYCLE

• Site - mitochondria
• Not activated by any hormone.
• Vital cycle of cell (occur in any state)
• TCA depends on
  • Energy status of cell. If energy is present, TCA will not occur & vice-versa.
  • Availability of oxaloacetate. Thus, oxaloacetate is also regarded as carrier of TCA cycle or 1^st Substrate of TCA cycle. Also, it plays a catalytic role in TCA cycle.

• Only occurs in aerobic state
• Not occurs in anaerobic state due to feedback regulation by NADH & FADH₂ which are unable to enter ETC as O₂ is absent.
• Important Information
  • Only 1 SLP occurs in TCA done by enzyme succinate thiokinase which mostly produces ATP but in liver & kidney during fasting/starvation state, it produces GTP as during this state, gluconeogenesis occurs & it requires GTP.
  • Acetyl CoA is not an intermediate of TCA cycle
  • 2 CO₂ which are removed in TCA comes from Oxaloacetate. If oxaloacetate not given, then mark acetyl CoA
• Inhibitors of TCA  

Important Information

Malate (4C): Intermediate of TCA Cycle

Malonate (3C): Inhibitor of TCA Cycle

Malonate / Malonyl CoA is an inhibitor of

• TCA Cycle (Enz inhibited is Succinate Dehydrogenase)
• ETC (component inhibited is Complex II)
• Beta Oxidation of Fatty Acids (Enz inhibited is CPT-1)

Important information

• 5 coenzymes are required for link reaction & TCA: Lipoic acid, B₁, B₂, B₃, B₅.
• Lethargy (low energy) is mostly diagnosed due to low levels of these vitamins and multivitamins supplementations are recommended as a remedy

Also Read : Important Topics in Biochemistry for AIIMS-PG by Dr. Smily Pruthi

ETC

• Located in Inner Mitochondrial Membrane (IMM)
• Components
  • 5 protein complexes labeled I to V 
  • 2 Mobile molecules are Coenzyme Q and Cytochrome C (Peripheral membrane protein) 

• Note: Coenzyme Q is the only non-protein component of ETC
  • In ETC, oxidation & phosphorylation occur together (coupled).
  • Uncoupling means that oxidation occurs but not phosphorylation.
• Uncouplers e.g.
  • Dinitrophenol (drug)
  • Natural/Physiological couplers
    • Thermogenin: present in brown fat in hibernating animals & in neonates & causes non-shivering thermogenesis
    • Thyroxine

Important Information

Q. ADP to ATP conversion in ETC is inhibited by?

Ans. Oligomycin (by inhibiting complex V which converts ADP to ATP)

Q. ADP to ATP transfer in ETC is inhibited by?

Ans. Atractyloside (by inhibiting ADP-ATP translocase)

Also Read : Biochemistry FAQs answered by Dr. Smily Pruthi

Inhibitors of ETC Complexes

Complex	Inhibitors
I	Rotenone, Phenobarbitone
II	Malonate (3C)
III	Phenformin
IV	Cyanide, CO, H2S, Na azide

GLUCONEOGENESIS

4 Enzymes of Gluconeogenesis which are different from Glycolysis

Enzyme	Feature
Pyruvate carboxylase	Present in mitochondria uses ATP activated by acetyl CoA
2.PEPCK (Phosphoenolpyruvate carboxykinase)	Both are present is cytoplasm
3.Fructose -1-6- Bisphosphatase
4.Glucose -6- phosphatase	present in endoplasmic reticulum (to prevent glucose-6-P breakdown to glucose) common enzyme of gluconeogenesis and Glycogenolysis Present in liver but absent in muscles

• Substrates of Gluconeogenesis
  • Pyruvate and Lactate
  • Glycerol and Propionic acid
  • Glycogenic amino acid
  • Both Glucogenic & Ketogenic amino acids
  • Any TCA intermediates

• Important Information
  • Most glucogenic amino acid- Alanine
  • If both leucine and lysine are given in options for ketogenic amino acid, mark leucine as it is more ketogenic
  • Total ketogenic AA= 2+5 = 7
  • Total Glucogenic AA = 13+5 = 18

Reciprocal regulation of Glycolysis & Gluconeogenesis

Enzyme	Feature
1.Pyruvate carboxylase	Present in mitochondria uses ATP activated by acetyl CoA
2.PEPCK (Phosphoenolpyruvate carboxykinase)	Both are present is cytoplasm
3.Fructose -1-6- Bisphosphatase
4.Glucose -6- phosphatase	present in endoplasmic reticulum (to prevent glucose-6-P breakdown to glucose) common enzyme of gluconeogenesis and Glycogenolysis Present in liver but absent in muscles

GLYCOGEN

• Stored mainly in liver & muscle and minor amount in brain
• End-product of liver glycogenolysis is glucose.
• Main purpose of liver glycogen is to maintain blood glucose
• End-product of liver glycogenolysis is glucose-6-phosphate.
• Main purpose of Muscle glycogen is to provide energy for muscle contraction.

Glycogen Synthesis

• RLE for glycogenesis: Glycogen synthase

Glycogenolysis

• Glycogenolysis enzymes
  • Glycogen Phosphorylase
    • RLE of glycogenolysis
    • Requires Vit B6
    • Breaks α (1-4) bond
    • Releases 90% of glucose in the form of glucose-I-PO₄ 
  • Debranching enzyme
    • Breaks α (1-6) bond
    • Releases 10% of glucose in the form of D-glucose

• Important Information
  • Both RLE for Glycogen metabolism are transferases
  • Both pathway of glycogen metabolism occurs in cytoplasm
  • For Glycogen Synthesis, a Primer Glycogenin (protein) is required.
  • Enzyme common between glycolysis and glycogenesis: hexokinase/ glucokinase.
  • Enzyme common between glycogenesis & glycogenolysis: phosphoglucomutase (interconverts glucose-1-P and glucose-6-P)

HMP

• Glucose 6–P (a hexose phosphate) is the starting material hence the name Hexose Monophosphate

Pathway

• Other name is Pentose Phosphate Pathway (PPP) as Pentose Phosphate i.e. Ribose 5–P is synthesized only by this pathway.
• Occurs in cytoplasm
• Produces NADPH in phase-I of HMP (irreversible oxidative phase)
• Produced Ribose-5-P in phase-II of HMP (reversible Non-oxidative phase)
• It’s an anabolic pathway thus is activated by insulin
• RLE: Glucose-6-P dehydrogenase (G6PD)
• Site of HMP: Liver, lactating mammary glands, adipose tissue, placenta, gonads & RBC.
• Tissues which are never site of HMP: Skin and Non-lactating mammary glands 

Also Read: Amino Acid Disorders - NEET PG Biochemistry

In G6PD deficiency

• Oxidative Stress is main reason for hemolysis
• G6PD deficiency→ ↓ NADPH production in RBC → ↓ reduced glutathione → ↑ H₂O₂ → cause cell

membrane lysis and hemolysis

SORBITOL PATHWAY

• Aldose reductase generally present in all cells
• Sorbitol dehydrogenase present only in liver and testis (as fructose is main energy source for sperms)

Important Information

Clinical significance of polyol pathway:

• In patient with uncontrolled diabetes, excess blood glucose enters insulin-insensitive tissues such as peripheral nerves, renal glomeruli, lens and retina and leads to the formation of excess sorbitol by aldose reductase. But sorbitol dehydrogenase is absent in most of these cells and sorbitol cannot be converted to fructose. Hence, sorbitol accumulation occurs. 
• Sorbitol is hygroscopic and will absorb water causing cell swelling ultimately leading to complications such as retinopathy, neuropathy, nephropathy and also snow-flake cataract in diabetic patients. 

Previous Year’s Question

Q. Amino acid linking kreb’s cycle & urea cycle?    (NEET Jan 2019)

1. Aspartate
2. Fumarate 
3. Alanine
4. Arginine

Q. All are features of gluconeogenesis except? (JIPMER Dec 2019)

1. Gluconeogenesis is synthesis of glucose from non-carbohydrate source
2. Mainly takes place in liver
3. Seen in fasting state
4. Step are simple reversal of glycolysis

Q. Glucose is stored in Glycogen form, why? (AIIMS June 2020)

1. Compact
2. Can be reduced from multiple branches lends
3. Can be stored ale multiple Sites
4. Can provide glucose an muchas needed and when needed for 1 week

Q. Complex IV in Election Transport chain is inhibited by? (FMGE Dec 2020)

1. Cyanide 
2. Barbiturates 
3. Phenylnitrone 
4. Malonate

Q. Enzymes used in gluconeogenesis are? (INICET Nov 2020)

1. Hexokinase
2. PEPCK
3. Pyruvate carboxylase
4. GLU-6 Phosphatase 
5. Pyruvate kinase

Q. Enzyme present in both glycolysis and gluconeogenesis? (AIIMS June 2020)

1. PFK
2. PEP-CK
3. Phosphoglycerate kinase 
4. Pyruvate kinase

Q. Cytochrome C oxidase is inhibited by all EXCEPT? (INICET July 2021)

1. Methane
2. H₂S
3. CO
4. Cyanide

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